High rates of resistance to antibiotics are associated with healthcare-related infections, thus appealing for the urgent need for effective antimicrobials against these maladies. The present study aims to determine the chemical composition of essential oil (EO) from Clausena anisata leaves, and evaluate their antibacterial activity against selected nosocomial bacteria. Fresh leaves of Clausena anisata were subjected to a steam distillation using a Clevenger apparatus to afford the essential oil. The phytochemical composition of this oil was analyzed using gas chromatography-mass spectrometry (GC-MS). The essential oil was further tested against selected nosocomial bacteria, including Staphylococcus and Klebsiella species, among others, using a microdilution method. As a result, 0.77% of essential oil was extracted from fresh leaves of Clausena anisata. The GC-MS analysis revealed that the as-prepared essential oil contain E-anethole (70.77%), methyl isoeugenol (13.85%), estragole (4.10%), γ-terpinene (3.33%), myrcene (2.82%) and sabinene (0.77%), with E-anethole being the major constituent. Meanwhile, twenty two compounds were identified in the EO of Clausena anisata leaves through gas chromatography. Upon antibacterial test against selected nosocomial pathogens, the E-anethole-rich essential oil exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 3.91 to 125 µg/mL and 7.81 to 125 µg/mL, respectively, indicative of a bactericidal orientation of the plant’s essential oil (MIC/MBC ratio: 4). This novel contribution highlights the scientific validation of the use of Clausena anisata leaves in the traditional treatment of various infectious diseases. However, toxicity and pharmacokinetic studies, mechanistic basis of the antibacterial action, and in vivo antibacterial experiments of the E-anethole-rich essential oil of Clausena anisata should be investigated to successfully use this plant in the treatment of infectious diseases.

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

The utilization of wild genera in sugarcane has been recognized as an important strategy to enhance the genetic base to impart biotic and abiotic stress tolerance in hybrid cultivars. A set of 15 Erianthus procerus derived hybrids along with five popular check varieties were evaluated for two years (2018–19 and 2019–20) for agro-morphological, quality, physiological traits and three years (2018–19, 2019–2020, and 2020–21 for winter sprouting potential. The E. procerus hybrid GU 12-19 recorded the highest winter sprouting potential with a winter sprouting index (WSI) of 10.6 and a percent superiority of 279 over best check (Co 0238) followed by GU 12-22 with WSI: 8.5 and % superiority over best check was 204. The other top-performing hybrids, GU 12-21 and GU 12-29, recorded the excellent winter sprouting potential with WSI of 7.2 and 6.9 respectively. The four E. procerus hybrids identified with higher WSI were also resistant to the prevalent races of red rot in both tropical and subtropical conditions. The association analysis revealed significant correlations between various traits, particularly fibre content with a maximum number of associations, which indicates its multifaceted impact on sugarcane characteristics. Principal component analysis (PCA) summarized the data, explaining 57.6% of the total variation for measured traits and genotypes, providing valuable insights into the performance and characteristics of the E. procerus-derived hybrids under subtropical climate. The anthocyanin content of E. procerus hybrids was better than the check varieties with a mean of 0.147 (2018–19) and 0.144 (2019–20) and range of 0.123–0.179 (2018–19) and 0.111–0.172 (2019–20), anthocyanin plays a vital role in mitigating the cold injury, acting as an antioxidant in cool weather conditions, particularly in sugarcane. Further, seven hybrids recorded more than 22% fibre threshold, indicating their industrial potential. These hybrids would be potential donors for cold tolerance and high ratooning ability along with red rot resistance under subtropical climate.

The overhead squat movement engages various bodily structures, and its interaction with three-dimensional elastic resistance along the kinetic chain approach remains insufficiently comprehended. This study aimed to describe the scapular kinematics during an overhead squat with the forearm in a supination exercise against an ER and clarify the therapeutic potential of this exercise on scapular rehabilitation. Using an electromagnetic tracking system, we recorded the three-dimensional shoulder kinematics of 19 male participants across seven humeral elevation positions. These positions were captured at 15-degree intervals, spanning from 30 to 120 degrees. The results indicated notable distinctions in scapular upward rotation [F(1,17)=6.09, p=0.024] and scapular posterior tilt [F(1,17)=6.04, p=0.025] between the phases. Furthermore, the interactions revealed significant differences in resistance and phases during humeral elevation for scapular upward/downward rotation [F(3.77,62.48)=7.99, p<0.001], scapular internal/external rotation [F(2.98, 50.64, p<0.001)], and scapular tilt [F(2.58, 43.81)=4.76, p=0.008]. The findings demonstrated that increasing resistance through elastic resistance played a pivotal role in enhancing scapular stability throughout the humerus elevation motion. This underscores the potential of the overhead squat movement as a valuable tool for both shoulder assessment and treatment.

The issue of optimising the initial stand density (ISD) of tree plantations has high practical importance. The objective of this study was to nondestructively evaluate the influence of the initial stand density of Scots pine plantations located in the European part of the Russian Federation on wood basic density (BD), moisture content (MC), ultrasound velocity (UV), latewood content, and drilling resistance (DR). 45-year-old trees with stand densities of 500, 1000, 3000, 5000, and 10000 trees/ha were tested by a 5-cm-long core sample for gravimetric MCGM and BD, by PULSAR-2.2 for UV along the height (UVH) and through the tree trunk diameter (UVD), by the IML-RESI PD-400 tool for DR, and by GANN HT 85T for MC based on the electrical resistance method (MCERM). A significant influence of ISD was found on DBH, UVD, MCGM, and MCERM. ISD had no significant impact on BD, UVH, and DR. The wood BD ranged from 356 to 578 kg/m-3, with a mean value of 434±3.3 kg/m-3, and was restricted by the soil and environmental factors. DBH and 70% MCERM were good indicators of tree vitality. Linear correlations between DBH and MCERM (R2=0.67), DBH and MCGM (R2=0.74), DR and BD (R2=0.71), and the two-factor model MCGM=f(DBH, BD), (R2=0.76) were found.

Fusarium spp. are commonly associated with the root rot complex of soybean (Glycine max). Previous surveys identified six common Fusarium species from Manitoba, including F. oxysporum, F. redolens, F. graminearum, F. solani, F. avenaceum and F. acuminatum. This study aimed to determine their pathogenicity, assess host resistance and evaluate the genetic diversity of Fusarium spp. isolated from Canada. Pathogenicity was tested on two cultivars, ‘Akras’ (moderate resistance) and ‘B150Y1’ (susceptible), under greenhouse conditions. The virulence of the fungal isolates varied, with root rot severities ranging from 1.5 to 3.3 on a 0-4 scale. The six species were used to screen a panel of 20 Canadian soybean cultivars for resistance in a greenhouse. Cluster and principal component analyses were conducted based on the same traits as for the pathogenicity study. Two of the cultivars, ‘P15T46R2’ and ‘B150Y1’, were consistently found to be tolerant to F. oxysporum, F. redolens, F. graminearum and F. solani. To investigate the incidence and prevalence of Fusarium spp. in Canada, fungi were isolated from 106 soybean fields surveyed across Manitoba, Saskatchewan, Ontario and Quebec. Two-hundred twenty-one Fusarium isolates were identified, with phylogenetic analyses indicating diversity of the isolates in the major soybean production regions of Canada.

Resistance evolution during exposure to non-lethal levels of antibiotics is influenced by various stress responses of bacteria which are known to affect growth rate. Here, we aim to disentangle how the interplay between resistance development and associated fitness costs is affected by stress responses. We performed de novo resistance evolution of wild-type strains and single-gene knockout strains in stress response pathways using four different antibiotics. Throughout resistance development, the increase in minimum inhibitory concentration (MIC) is accompanied by a gradual decrease in growth rate, most pronounced with amoxicillin or kanamycin. By measuring biomass yield on glucose and whole-genome sequences at intermediate and final timepoints, we identified two patterns of how the stress responses affect the correlation between MIC and growth rate. First, single-gene knockout E. coli strains associated with reactive oxygen species (ROS) acquire resistance faster and mutations related to antibiotic permeability and pumping out occur earlier. This increases the metabolic burden of resistant bacteria. Second, the ΔrelA knockout strain which has reduced (p)ppGpp synthesis, is restricted in its stringent response, leading to diminished growth rates. The ROS-related mutagenesis and the stringent response are vulnerabilities within the fitness of resistant strains that can possibly be targeted to prevent development of resistance.

(1) Background: The typical transporter protein, P-glycoprotein (P-gp), has been proven to be associated with multidrug resistance (MDR). Pyxinol and 24S-Pyxinol amino acid ester derivatives had been demonstrated to be promising P-gp inhibitors for reversal of tumor MDR in KBV cells, however, their roles in MDR reversal in other tumor-resistant cells are still unclear. (2) Methods: In the present study, we synthesized 40 amino acid ester derivatives of Pyxinol and 24S-Pyxinol. The MDR reversal effects of these derivatives were evaluated in A549/Tax, MCF-7/ADR, and HCT-8/VCR cells using the CCK-8 assay. Subsequently, western blot assay, intracellular Rhodamine123 (Rh123) accumulation assay and P-gp ATPase activity assay were utilized to investigate the effects of active compound on P-gp. Molecular docking was used to predict the possible binding patterns of active compound to P-gp. Moreover, based on UPLC-Q/TOF-MS cellular metabolomics technology to identify endogenous differential metabolites and metabolic pathways associated with tumor MDR effects of the active compound. (3) Results: The results of the CCK-8 assay showed that compounds 8, 14, 16, 17, 18, 23, 25, 34, 36, 37 exhibited strong MDR reversal effect in A549/Tax, MCF-7/ADR and HCT-8/VCR cells, which were screened by reversal fold (RF) greater than 5. Among them, 10 μM of derivative 37 (new compound) showed the outstanding activity (RF: 15.31) in reversing MDR in A549/Tax cells. Compound 37 could act as a substrate for P-gp and inhibit the efflux function of P-gp by competitively binding to the binding site of antitumor drugs. Meanwhile, the molecular docking results confirmed that compound 37 was identified to under-go high-affinity binding to the drug binding site of P-gp. In addition, 14 endogenous differential metabolites and 6 metabolic pathways involved closely associated with the reversal of tumor MDR effects of compound 37 were identified. (4) Conclusions: Overall, a new candidate compound 37 (24S-3-L-threonyl-Pyxinol) could be provided for reversing tumor MDR by this study.

Polycystic ovary syndrome (PCOS) is increasingly being viewed as an evolutionary mismatch disorder that manifests in women after exposure to a range of lifestyle and environmental factors. Although there is ongoing debate regarding the pathogenesis, international guidelines recommend lifestyle treatment, with diet and exercise, as the first line of management in all women with PCOS. In addition, accumulating evidence suggests that environmental factors such as endocrine disrupting chemicals (EDC) may be involved in the pathogenesis of PCOS due to their known hormonal and metabolic effects. As a result, international professional bodies have recommended that all pregnant women be advised of the risks of EDC and that education programs be developed to inform health professionals. Microparticulate air pollution (MAP) is also a significant environmental exposure that has been associated with a variety of chronic diseases, including PCOS. We performed a systematic review of studies examining the relationship between MAP and PCOS using the PRISMA methodology. The review identified 214 records from PubMed, Cochrane, and Scopus databases, and 4 studies that met the inclusion criteria for qualitative assessment. Preliminary data suggest that MAP may contribute to the pathogenesis of PCOS via a number of mechanisms. This review highlights the need for greater awareness and further research on the effects of MAP in women with PCOS.

The regenerated magnesia-calcium brick samples that had added 0, 1.5, 3.0 wt.% aluminium oxide (Al2O3) were prepared by using spent magnesia-calcium bricks, fused magnesia and Al2O3 powder additive as the main raw materials. The phases, microstructures, room temperature and hot flexural strength, resistance to cement clinker corrosion and strength of coating adherence were investigated respectively. It indicated that the addition of Al2O3 increased mainly resulting in the content of tetracalcium aluminoferrite (C4AF) and tricalcium aluminate (C3A) increased in the regenerate samples. The bulk density, the room temperature flexural strength and the strength of coating adherence all increased, while the hot flexural strength and corrosion resistance both deteriorated along with the increase of Al2O3 addition. It was because that on the one hand the low melting point phases of C4AF and C3A improved the sinterability of the regenerated samples during the burning stage, on the other hand they melted or existed in liquid phase during the experimental temperature (1573 K and 1823 K) which degraded hot flexural strength and corrosion resistance, and enhanced the strength of coating adherence as the wettability of the liquid phase. The content of Al2O3 in the regenerated magnesia-calcium brick should not be higher than 1.1 wt.%, considering its room and high-temperature performances for cement rotary kiln.

New antibiotics are unquestionably needed in the fight to the emergence and spread of multidrug-resistant bacteria. So far, antibiotics targeting bacterial central metabolism have been poorly investigated. By determining the minimal inhibitory concentration (MIC) of desmethylphosphinothricin (Glu-γ-PH), an analogue of glutamate with a phosphinic moiety re-placing the γ-carboxyl group, we previously showed its promising antibacterial activity on Escherichia coli. Herein we synthetized and determined the growth inhibition exerted on E. coli by an L-Leu dipeptide derivative of Glu-γ-PH (L-Leu-D,L-Glu-γ-PH). Furthermore, we compared the growth inhibition obtained with this dipeptide with that exerted by the free amino acid, i.e. Glu-γ-PH, and by their phosphonic and non-desmethylated analogues. All tested compounds were more effective when assayed in chemically defined minimal medium. The dipeptide L-Leu-D,L-Glu-γ-PH had a significantly improved antibacterial activity (2 μg/mL), at a concentra-tion between the non-desmethytaled (0.1 μg/mL) and the phosphonic (80 μg/mL) analogues. Also in Bacillus subtilis the dipeptide L-Leu-D,L-Glu-γ-PH displayed an activity comparable to that of the antibiotic amoxicillin. This work highlights the antibacterial relevance of the phosphinic pharmacophore and proposes new avenues to the development of novel antimicrobial drugs containing the phosphinic moiety.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates. A major causative agent of UTIs is uropathogenic Escherichia coli (UPEC), which can form persistent biofilms on urothelial surfaces and/or urinary catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Ciprofloxacin hybrids functionalised with nitroxides have previously shown enhanced biofilm eradication activity in vitro. Here, we evaluate a ciprofloxacin di-nitroxide hybrid (CDN11), previously reported to have antibiofilm activity against UPEC, as a potential UTI therapeutic in various infection models. We report potent CDN11 activity against mature biofilms formed by cystitis strain UTI89 inside polyethylene catheters. In infected human bladder cell monolayers, CDN11 afforded a 3-log reduction in UPEC colony forming units (CFU) compared to controls, including intracellular bacteria. Infected mouse bladders carrying biofilm-like intracellular UPEC reservoirs had reduced bacterial burdens following treatment with CDN11 ex vivo. Activity trends for CDN11 were comparable throughout all models, indicating that our testing pipeline was robust. New antimicrobial development is arduous and requires large investments of time and money. The pipeline described here could be readily used in testing new compounds, fast tracking the development of novel UTI therapeutics.

The global prevalence of insulin resistance (IR) is increasing continuously, influencing metabolic parameters and fertility as well. The metabolic changes due to IR can alter the molecular composition of plasma and other body fluids. Follicular fluid (FF) is derived mainly from plasma, and it is a critical microenvironment for the developing oocytes. It contains various metabolites and amino acids, and the quality of the oocytes is linked at least partially to amino acid metabolism. Our goal was to determine quantitatively the amino acid (AA) profile of FF in IVF patients and to compare IR and non-insulin resistance (NIR) groups to investigate the AA changes in their FF. By UHPLC-based method we quantified the main 20 amino acids from human FF samples in the IR and NIR groups. Several amino acids (aspartate, glycine, glutamate, and cysteine) differed significantly (p<0.05 or less) between the two groups. The most significant alterations between the IR and NIR groups were related to the glutathione metabolic pathway involving glycine, serine, and threonine. Since insulin resistance alters the amino acid composition of the FF, the oocytes may undergo metabolism-induced changes resulting in poor oocyte quality and less fertility in the insulin resistance groups.

Antimicrobial resistance (AMR) remains a challenge in Kenya, while the extent remains unknown. To assess the knowledge, cultural beliefs, practices, and behavioral patterns among multisectoral stakeholders in Kenya. The cross-sectional survey was conducted in August 2021 among farmers, animal health service providers and AMR researchers. Regional digital data collection tool developed by FAO was shared and responses obtained through mail, phone calls and direct interviews. Descriptive and inferential analysis were conducted. Antimicrobials were mostly sourced from agro-veterinary shops and from veterinary professionals. Farmers, often implement self-treatment and reported overuse, unnecessary use, and sometimes fail to complete the dosage in livestock. More farmers reported to have heard about antibiotics as compared to antimicrobials, mostly from friends and radio program, however only 9.2% could correctly differentiate the two. Animal Health Service Providers (AHSP) were the source of information to farmers regarding AMR. AHSPs mainly relied on suppliers and distributors for information about antibiotics. Both farmers and AHSPs treated viral infections with antibiotics. One Health Partners (OHPs) had higher knowledge and largely favorable attitudes towards AMR. Up to 72.7% of OHPs from training institutions had AMR included in training curriculum however, they were optimistic livestock farmers and government were less concerned about AMR. Gaps in knowledge and practice on Antimicrobial Stewardship (AMS) were observed in all categories of stakeholders. Given the documented knowledge-practice gap, innovative solutions are needed for both AHSPs and farmers to promote good antimicrobial stewardship practices and to mitigate burdens of AMR. Outcomes of this research should deepen the understanding of critical information and trigger behavioral change in usage and stewardship of antimicrobials.

Fungi constitute a diverse group with highly positive and negative impacts in different envi-ronments, having several natural roles and beneficial applications in human life, but also caus-ing several concerns. Fungi can affect human health directly, but also indirectly by being detri-mental for animal and plant health influencing food safety and security. Climate changes are al-so affecting fungal distribution, prevalence, and their impact on different settings. Searching for sustainable solutions to deal with these issues is challenging due to the complexity of the inter-actions among fungi and agriculture, animal production, environment, and human health. In this way, the “One Health” approach may be useful to get some answers since it recognizes that human health is closely connected to animal and plant health, as well as to the shared environ-ment. This review aims to explore and correlate each of those factors influencing human health in this “One Health” perspective.

Background: The diagnosis of metabolic syndrome (MetS) is a challenge in people with spinal cord injury (SCI). We aimed at identifying clinical risk factors or early markers of MetS in SCI that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. Methods: 168 patients with chronic (>1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Results: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in minutes/week (OR: 0.998, 95%CI: 0.996, 0.999) and more severe pain symptoms as assessed by numeral rating scale (OR: 1.353, 95%CI: 1.085, 1.793). Conclusions: In patients with SCI, intense pain symptoms and poor LTPA may suggest a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insu-lin-sensitivity and comorbidities.

There is a growing interest in a potential use of essential oils (EOs) as a possible alternative for chemical pesticides. The formulation between different EOs could maximize the single biological efficacy by synergic mechanism. The aim of the current study was to evaluate the biological activity of three prepared blended oil formulations (BOFs) derived from Origanum vulgare L. (oregano) and Salvia officinalis L. (sage) compared to each parent EO. The chemical composition of each single studied EO has been revealed using GC-MS analysis. The three BOFs have been prepared as following: i) 25% oregano EO + 25% sage EO (BOF-I); ii) 25% oregano EO + 5% sage EO (BOF-II); iii) 5% oregano EO + 25% sage EO (BOF-III). The antibacterial activity of the new BOFs has been evaluated against Bacillus megaterium, B. cereus and Xanthomonas campestris, whereas, the antifungal activity has been carried out against Botrytis cinerea, Penicillium italicum and Fusarium oxysporum. The possible phytotoxic effect of the new BOFs has been evaluated on Lepidium sativum (garden cress), Solanum lycopersicum (tomato) and Lactuca sativa (lettuce) following the seed germination and radicle elongation assay. GC-MS analysis revealed that the oregano EO composed mainly from thymol, p-cymene and carvacrol with 76.0, 5.7 and 3.2 %, respectively. Whereas, salvia EO, the GC-MS analysis showed that the relevant predominant constituents were trans-thujone and camphor with 37,9 and 13,9 %, respectively. Results demonstrated that the tested BOFs possess antimicrobial effect higher than each parent EO. In particular, BOF-II showed the highest effect against all tested bacteria. Regarding the antifungal activity, BOF-II showed the highest significant antifungal effect against all tested fungi. Results showed also that both BOF-I and BOF-III explicated a moderate effect against B. cereus and all tested fungi compared to single EOs. In addition, the three BOFs showed notable phytotoxic effect against all three tested plants, particularly BOF-I. Whereas, the single sage EO at 25% showed the lowest significant phototoxic effect indicating its possible using as natural herbicides.

The gate resistance is a parasitic element in transistors for RF and millimeter-wave circuits that can negatively impact power gain and noise figure. To develop accurate device models, a reliable measurement methodology is crucial. This article reviews the standard measurement methodology used in the literature and proposes also an additional method, which is evaluated using suitable test structures in a 16nm FinFET process. The advantages and disadvantages of the two approaches are discussed along with their respective application scenarios

This paper presents the results of an experimental and analytical study on the behavior of cold-formed thick-walled steel plates connected by a single bolt under double shear. Experimental studies were conducted on a total of 54 bolted connections fabricated from two thickness of cold-formed thick-walled steel plates with the nominal thickness of 6 mm and 10 mm. The effects of end distance, edge distance and steel plate thickness were investigated on the bolt bearing behavior. Codes of (modified) ANSI/AISC 360-16 and EN1993-1-8 were applied to predict failure modes and bearing resistance of connections and the predictions were compared with that of measurements. A method was proposed to calculate the elongation of bolt hole at ultimate load. The studies show that fractures occurred on shear planes of specimens failed by shear out due to reduced ductility caused by cold forming process. The modified ANSI/AISC gives the most accurate predictions of failure modes and bearing resistance. However, the bearing resistance will be overestimated if the reduction in area of shear planes caused by occurrence of fracture is ignored for specimens with end distance being higher than 2.0d0 and a reduction factor is needed for calculating bearing resistance of connections. The method proposed in our paper can predict the elongation of bolt hole very well.

This study investigates the effects of the antiperspirant aluminum chlorohydrate on the development of antibiotic resistance in commensal Staphylococcus epidermidis isolates. The isolates were exposed to aluminum chlorohydrate for 30 days, respectively. The bacteria that developed resistance to oxacillin, and ciprofloxacin were isolated, and the expression levels of some antibiotic resistance genes were determined by quantitative reverse transcriptase-PCR. Before and after the exposure, the minimum inhibitory concentration (MIC) values of the bacteria were determined by the microdilution method. A time-dependent increase was observed in the number of bacteria that developed resistance and increased the MIC value. Consistent with the ciprofloxacin resistance observed after exposure, an increase in the norA, norB/C, gyrA, gyrB, parC, and parE gene expressions was observed. In addition to aluminum chlorohydrate exposure, oxacillin resistance was observed in all test bacteria in the group subcultured only in the medium, suggesting that phenotypic resistance cannot be correlated with chemical exposure in the light of these data. The increase in mecA gene expressions of selected test bacteria that acquired resistance to oxacillin after exposure compared with control groups suggests that the observed resistance may be related to aluminum chlorohydrate exposure. To our knowledge, this is the first time in the literature that the effects of aluminum chlorohydrate as an antiperspirant on the development of antibiotic resistance in Staphylococcus epidermidis have been reported.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. Coupled with the increasing burden of healthcare with aging populations and the protracted course the infections may take, these infections contribute to a significant challenge for healthcare. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions is identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents is also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in the near future.

Healthcare-associated infections (HAI) worldwide includes infections by ESKAPE-E pathogens. Environmental surfaces and fomites are important components in HAI transmission dynamics, and shoe soles are vectors of HAI. Ultraviolet (UV) disinfection is an effective method to inactivate pathogenic microorganisms. In this study, we investigated whether the SANITECH UVC shoe sole decontaminator equipment that provides germicidal UVC radiation could effectively reduce this risk of different pathogens. Six standard strains and four clinical MDR strains in liquid and solid medium were exposed to a UVC System at specific concentrations at other times. Bacterial inac-tivation (growth and cultivability) was investigated using colony counts and resazurin as meta-bolic indicators. SEM was performed to assess the membrane damage. Statistically significant reduction in cell viability for all ATCCs strains occurred after 10 sec of exposure to the UVC sys-tem, except for S enterica, which only occurred at 20 sec. The cell viability of P. aeruginosa (90.9%), E. faecalis and A. baumannii (85.3%), S. enterica (82.9%), E. coli (79.2%) and S. aureus (71.9%) was re-duced considerably at 20 sec. In colony count, after 12 sec of UVC exposure, all ATCC strains showed a 100% reduction in CFU counts, except for A. baumannii, which reduced 97.7%. A sub-stantial reduction of colonies above 3 log10 was observed at 12 and 20 sec in all bacterial strains tested, except for A. baumannii ATCC 19606 (12 sec). The exposure of ATCCs bacterial strains to the UVC system for only 2 sec was able to reduce 100% in the CFU count in all ATCCs strains, S. au-reus, P. aeruginosa, E. coli, A. baumannii, E. faecalis, except the S. enterica strain which had a statis-tically significant reduction of 99.7%. In ATCC strains, there was a substantial decrease in colonies after 4 sec (sec) of exposure to the UVC system, with a reduction ranging from 3.78-4.15 log10 CFU/mL. This reduction was observed in MDR/ESKAPE-E strains within 10 sec, showing that UVC could eliminate above 3.84 log10 CFU/mL. SEM showed a reduction of pili-like appendages after UVC treatment in all strains except for E. coli (ATCC 25922). The Sanitech UVC shoe sole decontaminator equipment from Astech Co. effectively killed in vitro a series of ATCCs and MDR/ESKAPE-E bacteria of sanitary interest, commonly found in the hospital environment.

To realize structural vibration control,a two parameters H2 optimization design was proposed to optimize the tuning ratio and damping ratio for electromagnetic tuned mass damper (EMTMD). The control effect of this two parameters optimization design is better than that of classical tuned mass damper (TMD).For this two parameters optimization,the most important thing is that the inductance of the coil can be set very small and the external load resistance can be positive ,which can avoid the use of complex negative impedance circuit. If Ref.[6] were designed according to the H2 optimization of two parameters, the EMTMD can be used for multi-modal vibration control of structures without connecting negative inductance and negative resistance spontaneously.

Members of the insect ATP binding cassette transporter subfamily C2 (ABCC2) in several moth species are known as receptors for the Cry1Ac insecticidal protein from Bacillus thuringiensis (Bt). Mutations that abolish the functional domains of ABCC2 are known to cause resistance to Cry1Ac, although the reported levels of resistance vary widely depending on insect species. In this study, the function of the ABCC2 gene as putative Cry1Ac receptor in Helicoverpa zea, a major pest of over 300 crops, was evaluated using CRISPR/Cas9 to progressively eliminate different functional ABCC2 domains. Results from bioassays with edited insect lines support that muta-tions in ABCC2 was associated with Cry1Ac resistance ratios (RR) ranging from 7.3- to 39.8-fold. No significant differences in susceptibility to Cry1Ac were detected between H. zea with partial or complete ABCC2 knockout, although highest levels of tolerance were observed when knocking out half of ABCC2. Based on >500-1,000-fold RRs reported in similar studies for closely related moth species, the low RRs observed in H. zea knockouts support that ABCC2 is not a major Cry1Ac receptor in this insect.

Weeds are among the major constraints to any crop production system, reducing productivity and profitability. Herbicides are among the most effective methods to control weeds, and reliance on herbicides for weed control has increased significantly with the advent of herbicide-resistant crops. Unfortunately, over-reliance on herbicides leads to environmental-health issues and herbicide-resistant weeds, causing human-health and ecological concerns. Crop diversification can help manage weeds sustainably in major crop production systems. It acts as an organizing principle under which technological innovations and ecological insights can be combined to manage weeds sustainably. Diversified cropping can be defined as the conscious inclusion of functional biodiversity at temporal and/or spatial levels to improve the productivity and stability of ecosystem services. Crop diversification helps to reduce weed density by negatively impacting weed seed germination and weed growth. Additionally, diversified farming systems are more resilient to climate change than monoculture systems and provide better crop yield. However, there are a few challenges to adopting a diversified cropping system, which ranges from technology innovations, government policies, farm-level decisions, climate change, and market conditions. In this review, we discuss how crop diversification supports sustainable weed management, the challenges associated with it, and the future of weed management with respect to the diversification concept.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter that is responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the co-effects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of the mouse retina. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same condition to 8–12 wk (young) or 45–55 wk (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to that from aged WT mice, and subsequence gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision, and transcellular barrier function that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the 4 age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, although coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly to multidrug-resistant Gram-negative bacteria, and lastly to a possibly fatal Candida glabrata. Development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

The ectoparasitic mite Varroa destructor is the most significant pathological threat to the western honey bee, Apis mellifera, leading to the death of most colonies if left untreated. An alternative approach to chemical treatments is to selectively enhance heritable honey bee traits of resistance or tolerance to the mite through breeding programs, or select for naturally surviving untreated colonies. We conducted a literature review of all studies documenting traits of A. mellifera populations either selectively bred or naturally selected for resistance and tolerance to mite parasitism. This allowed us to conduct an analysis of the diversity, distribution and importance of the traits in different honey bee populations that can survive V. destructor throughout the globe. In a second analysis, we investigated the genetic bases of these different phenotypes by comparing ’omics studies (genomics, transcriptomics, and proteomics) of A. mellifera resistance and tolerance to the parasite. Altogether, this review provides a detailed overview of the current state of the research projects and breeding efforts against the most devastating parasite of A. mellifera. By highlighting the most promising traits of varroa-surviving bees and our current knowledge on their genetic bases, this work will help direct future research efforts and selection programs to control this pest. Additionally, by comparing the diverse populations of honey bees that exhibit the traits, this review highlights the consequences of anthropogenic and natural selection on the interactions between hosts and parasites.

Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens, in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens.

Water availability is a major constraint for spring wheat production on the western Loess Plateau of China. The impact of tillage practices on water potential, water potential gradient, water transfer resistance, yield, and water use efficiency (WUEg) of spring wheat was monitored on the western Loess Plateau in 2016 and 2017. Six tillage practices were assessed, including conventional tillage with no straw (T), no-till with straw cover (NTS), no-till with no straw (NT), conventional tillage with straw incorporated (TS), conventional tillage with plastic mulch (TP), and no-till with plastic mulch (NTP). No-till with straw cover, TP, and NTP significantly improved soil water potential and root water potential at the seedling stage and leaf water potential at the seedling, tillering, jointing, and flowering stages, compared to T. These treatments also significantly reduced the soil-leaf water potential gradient at the 0-10 cm soil layer at the seedling stage and at the 30-50 cm soil layer at flowering, compared to T. Thus, NTS, TP, and NTP reduced soil-leaf water transfer resistance and enhanced transpiration. Compared to T, the NTS, TP, and NTP treatments significantly increased biomass yield (BY) by 18, 36, and 40%, respectively, and grain yield (GY) by 28, 22, and 24%, respectively, with corresponding increases in WUEg of 24, 26, and 24%, respectively. These results demonstrate that NTS, TP, and NTP improved GY and WUEg of spring wheat by decreasing the soil-leaf water potential gradient and soil-leaf water transfer resistance and enhancing transpiration, and are suitable tillage practices for sustainable intensification of wheat production in semi-arid areas.

Abstract Due to the relatively low efficiency of thermoelectric (TE) generators, they have mostly been used in niche applications where the unique properties of TE generators outweigh their lack of efficiency, or conditions where it is more reasonable to base the optimal design on maximum generated power rather than maximum efficiency. The aim of this work is to investigate how the different fundamental transport properties (Seebeck coefficient, thermal conductivity and electrical resistivity) in materials with equal figure of merit (ZT) impact TE module design and maximum power output. Further, we discuss and review the strategies to enhance material properties and the latest studies on the TE module performance. It is shown, that by increasing the power factor by a factor of 15 and decreasing the thermal conductivity by 13.33 in order to maintain ZT=1, power output is increased by 45%. This effect is stronger in lower module fill factor and thermal resistance of the heat source and heat sink.

Commercially pure (c.p.) iron powders with a deliberate high degree of oxidation were consolidated by medium-frequency electrical resistance sintering (MF-ERS). This is a consolidation technique where pressure, and heat coming from a low-voltage and high-intensity electrical current, are simultaneously applied to a powder mass. In this work, the achieved densification rate is interpreted according to a qualitative microscopic model, based on the compacts global porosity and electrical resistance evolution. The effect of current intensity and sintering time on compacts was studied on the basis of micrographs revealing the porosity distribution inside the sintered compact. The microstructural characteristics of compacts consolidated by the traditional cold-press and furnace-sinter powder metallurgy route are compared with results of MF-ERS consolidation. The goodness of MF-ERS versus the problems of conventional sintering when working with oxidized powders is analyzed. The electrical consolidation allows to obtain higher densifications than the traditional route under non-reducing atmospheres.

Insulin resistance is the most important underlying cause of obesity and type 2 Diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits, widely known for their antioxidant properties, have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety, compliance and efficacy of mangosteen on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. 22 patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (HOmeostatic Model Assessment-Insulin Resistance, HOMA-IR -53.22% vs -15.23%, p=.0037), and a trend decrease in inflammation markers serum levels, together with trend greater weight loss and trend increased HDL levels. No side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible role of mangosteen in the treatment of obesity, insulin resistance and inflammation.

The incidence of obesity which leads to insulin resistance (IR) and metabolic disorder increases in developing countries including Indonesia. Male adult has higher risk to have abdominal obesity than female which is associated with cardiometabolic disorders. Several anthropometric measurements have been proposed to predict IR. The aim of this study was to investigate whether body mass, body mass index (BMI), waist circumference (WC), body fat percentage (BF) or visceral fat percentage (VF) could become a better predictor of IR in healthy young male adult. Total of 140 healthy young male adults ranging from 18-25 years were recruited in the study. Insulin resistance was measured by calculating Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Subjects with HOMA-IR value >75th percentile with cut off 3.75 were defined as IR. Anthropometric measurements included body weight, BMI, WC were performed whereas BF and VC were measured by bioelectrical impedance analysis (BIA). IR had significant strong correlation with body weight, BMI, WC, BF and VF. The area under curve of body mass, BF, VF were greater than WC and BMI. Anthropometric measurements correlated strongly with IR but body weight, BF, VF have stronger correlation than WC and BMI in healthy young male adult.

Multidisciplinary Design Optimization (MDO) is the most active field in the design of current complex system engineering, which is possessed with such two difficulties as subsystem information exchange and analytical and computational complexity of systems. Therefore, an improved collaborative optimization algorithm based on ANN (artificial neural network) response surface was proposed dependent on the consistency constraint algorithm and concurrent subspace algorithm. As an optimization method with secondary structure, it satisfied only local constraints in discipline layer, but provided a coordinated mechanism for interdisciplinary conflict in system layer. Finally, it was applied in the multidisciplinary design optimization of autonomous underwater vehicle (AUV). As shown from the result, the MDO convergence stability and reliability of low resistance, low noise and high maneuvering performance of the AUV shape can be ensured by the improved collaborative optimization algorithm, thus verifying the effectiveness of the algorithm.

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

Fusarium wilt of banana is a devastating disease that has decimated banana production worldwide. Host resistance to Fusarium oxysporum f. sp. cubense (Foc), the causal agent of this disease, is genetically dissected in this study using two Musa acuminata ssp. malaccensis segregating populations segregating for Foc Tropical (TR4) and Subtropical (STR4) race 4 resistance. Marker loci and trait association using 11 SNP-based PCR markers allowed the candidate region to be delimited to a 12.9 cM genetic interval corresponding to a 959 kb region on Chromosome 3 of ‘DH-Pahang’ reference assembly v4. Within this region, there is a cluster of pattern recognition receptors, namely leucine rich repeat ectodomain containing receptor-like protein kinases, cysteine-rich cell wall associated protein kinases, and leaf rust 10 disease-resistance locus receptor-like proteins positioned in an interspersed arrangement. Their transcript levels were rapidly upregulated in the resistant but not in susceptible F2 progenies at the onset of infection. This suggests that one or several of these genes may control resistance at this locus. To confirm the segregation of single-gene resistance, we generated an inter-cross between the resistant parent ‘Ma850’ and a susceptible line ‘Ma848’, to show that the STR4 resistance co-segregated with marker ‘28820’ at this locus. Finally, an informative SNP marker 29730 allowed the locus specific resistance to be assessed in a collection of diploid and polyploid banana plants. Out of the 60 lines screened, 22 lines were predicted to carry resistance at this locus, including lines known to be TR4 resistant, such as ‘Pahang’, ‘SH-3362’, ‘SH-3217’, ‘Ma-ITC0250’, and ‘DH-Pahang/CIRAD 930’. Additional screening in the International Institute for Tropical Agriculture’s collection suggests that the dominant allele is common among in the elite ‘Matooke’ NARITA hybrids, as well as in other triploid or tetraploid hybrids derived from East African highland bananas. Fine-mapping and candidate gene identification will allow characterization of molecular mechanisms underlying TR4 resistance. The markers developed in this study can now aid the marker-assisted selection of TR4 resistance in breeding programs around the world.

Thanks to several Vitis vinifera backcrosses with an initial V. vinifera L. × V. rotundifolia (previously Muscadinia rotundifolia) interspecific cross, the MrRUN1/MrRPV1 locus (resistance to downy and powdery mildews) was introgressed in genotypes phenotypically close to V. vinifera varieties. To check the consequences of introgressing parts of the V. rotundifolia genome on gene expression during fruit development, we conducted a comparative RNA-seq study on single berries from different V. vinifera cultivars and V. vinifera × V. rotundifolia hybrids, including ‘G5’ and two derivative microvine lines, ‘MV102’ (resistant) and ‘MV32’ (susceptible) segregating for the MrRUN1/RPV1 locus. RNA-Seq profiles were analyzed on a comprehensive set of single berries from the end of the herbaceous plateau to the ripe stage. Pair-end reads were aligned both on V. vinifera PN40024.v4 reference genome, V. rotundifolia cv ‘Trayshed’ and cv ‘Carlos’, and to the few resistance genes from the original V. rotundifolia cv ‘52’ parent available at NCBI. Weighted Gene Co-expression Network Analysis (WGCNA) led to classifying the differentially expressed genes into 15 modules either preferentially correlated with resistance or berry phenology and composition. Resistance positively correlated transcripts predominantly mapped on the 4-5 Mb distal region of V. rotundifolia chromosome 12 beginning with the MrRUN1/MrRPV1 locus, while the negatively correlated ones mapped on the orthologous V. vinifera region, showing this large extremity of LG12 remained recalcitrant to internal recombination during the successive backcrosses. Some constitutively expressed V. rotundifolia genes were also observed at lower density outside this region. Genes overexpressed in developing berries from resistant accessions, either introgressed from V. rotundifolia, or triggered by these in the vinifera genome, spanned various functional groups, encompassing calcium signal transduction, hormone signaling, transcription factors, plant–pathogen-associated interactions, disease resistance proteins, ROS and phenylpropanoid biosynthesis. This transcriptomic insight provides a foundation for understanding the disease resistance inherent in these hybrid cultivars and suggests a constitutive expression of NIR NBS LRR triggering calcium signaling. Moreover, these results illustrate the magnitude of transcriptomic changes caused by the introgressed V. rotundifolia background in backcrossed hybrids, on a large number of functions largely exceeding the ones constitutively expressed in single resistant gene transformants.

Abstract Plant diseases are responsible for over 10% loss in global food production and have serious impacts on world-wide food security across several countries. Amongst these diseases, those caused by viroids are highly significant, accounting for extensive damage to crops every year and pose a major economic threat to agricultural crops. Combined infections with viroids, plant viruses and their satellites further exacerbate the situation. Vector transmission of viroids necessitates the use of pesticides, thus incurring high costs in addition to eliciting several detrimental effects on the ecosystem due to the noxious outcomes of pesticide use. The current review addresses the major economic impacts of viroids on crops, costs to the world economy and impacts on regions, farmers and consumers in addition to describing remediation measures to mitigate the losses caused by these subviral agents. Also described are issues relating to the pros and cons of pesticide use, the compelling need towards sustainable agricultrual practices while reducing pesticide use. In particular, the role of RNAi and genome editing technologies towards amelioration of agricultural loss is discussed.

Salmonella Typhimurium is a typical Gram-Negative bacterium associated with food-borne illness threatening public health. This pathogen is reported to have caused millions of infections and thousands of hospitalizations yearly in the United States alone. Salmonella Typhimurium has a sophisticated array of virulent factors, including its flagella, which contributes significantly to its pathogenicity. Cannabidiol (CBD), the non-psychoactive component of the cannabis plant, has attracted the interest of many researchers recently because of its antimicrobial properties. With the growing interest in exploring CBD’s antimicrobial properties, we, in this study, have delved into unravelling how prolonged exposure of Salmonella Typhimurium to CBD influences the expression of the flgA gene. We hypothesized that the exposure of Salmonella Typhimurium to CBD may result in flgA upregulation, causing the bacteria to withstand various stresses and potentially enhance its survival rates and pathogenicity. We have employed several assays, such as mRNA expression, motility assays, pH induction assays, nutrient starvation interventions, and biofilm analysis, to explore the influence of CBD on the pathophysiology of Salmonella Typhimurium. Our findings reveal that CBD-resistant strains exhibit enhanced resilience to extreme pH levels and motility and survive poorly under nutrient starvation, with more robust biofilm formation compared to the susceptible strains. The results contribute to the broader comprehension of CBD resistance mechanisms in bacteria. This work provides insight into the potential therapeutic interventions for controlling CBD-resistant bacterial infections. This study also underscores the essence of exploring novel alternative antimicrobial agents to tackle the ever-persistence of bacterial antibiotic resistance.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensively resistant (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definition. Sub-lineage 4.3 (52%) was the most frequent genotype and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected 20 novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. Cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug-resistance prediction, presenting the best accuracy values to five of nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) and genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil, genetic and clinical data correlations and demonstrating its utility for surveillance efforts for spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

Geopolymer concrete (GPC) represents an innovative green and low-carbon construction material, offering a viable alternative to ordinary Portland cement concrete in building applications. However, existing studies tend to overlook the recyclability aspect of GPC for future use. Various structural applications necessitate the use of concrete with distinct strength characteristics. The recyclability of the parent concrete is influenced by these varying strengths. This study examined the recycling potential of GPC across a spectrum of strength grades (40, 60, 80 and 100 MPa, marked as C40, C60, C80 and C100) when subjected to freeze-thaw conditions. The cementitious material comprised 60% metakaolin and 40% slag, with natural gravel serving as the coarse aggregate, and the alkali activator consisting of sodium hydroxide solution and sodium silicate solution. The strength of the GPC was modulated by altering the Na/Al ratio. After 350 freeze-thaw cycles, the GPC specimens underwent crushing, washing, and sieving to produce recycled geopolymer aggregates (RGAs). Subsequently, their physical properties and microstructure were thoroughly examined. The findings indicated that GPC with strength grades of C100, C80, and C60 were capable of enduring 350 freeze-thaw cycles, in contrast to C40, which did not withstand these conditions. RGAs derived from GPC of strength grades C100 and C80 complied with the criteria for Class II recycled aggregates, whereas RGAs produced from GPC of strength grade C60 aligned with the Class III level. A higher strength grade in the parent concrete correlated with enhanced performance characteristics in the resulting recycled aggregates.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

In the text, the synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilide derivatives of amino acids are described. They have shown inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range, as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, also including glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

This study aimed to investigate the fatigue performance and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar lap joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Furthermore, the fatigue life of the 14 kV joints was one order of magnitude higher compared to the 12 kV joints. SEM observation of the fatigue fracture surface revealed the presence of typical "tire-mark" fatigue striations only in the 14 kV joint, indicating higher ductility and the ability to withstand extended plastic deformation. Notably, ultra-fine nanocrystalline Al2Cu phase, amorphous phase, and numerous dislocations hindered EBSD acquisition in the transition zone. Nevertheless, dense low-angle grain boundaries (LAGBs) and refined grains were examined at the bonding interface. This suggests that the high-velocity collision caused severe plastic deformation and led to the formation of substructures. The interfacial strength was attributed not only to the "wave-like" or "inverted hook-like" diffusion layer but also to the presence of refined grains along the interface and nanocrystalline Al2Cu in the transition zone. Furthermore, the hybrid nanocrystalline-amorphous microstructure strengthened the joint by regulating the balance between strength and ductility.

This study investigated the fatigue properties and interfacial strengthening mechanisms of Al6061-to-Cu dissimilar welded joints via electromagnetic pulse welding (EMPW). The load-bearing capacity of the joints at discharge voltages of 14 kV and 16 kV was superior to that of 12 kV. Meanwhile, the fatigue life of 14 kV joints was one order of magnitude higher than that of 12 kV. The SEM observation on the fatigue fracture surface shows that the typical “tire-mark” fatigue striation just appeared on the 14 kV joint, indicating higher ductility for handling more extended plastic deformation. The high EBSD acquisition was achieved except for the transition zone due to the formation of ultra-fine nanocrystalline Al2Cu phase and amorphous phase, along with many dislocations. Dense low-angle grain boundaries (LAGBs) and refined grains are formed along the bonding interface. This indicates that severe plastic deformation induced dislocations to form the substructure in such an instant (40-60 μs) during the high-velocity collision. The interfacial strength is not only due to the continuous interfacial diffusion layer with a “wave-like” or “inverted hook-like” pattern but also benefits from refined grains along the interface and in the transition zone, as well as the hybrid amorphous-nanocrystalline microstructure, which strengthens the joint through increasing ductility induced by refined grains and regulating amorphous or nanocrystalline phases to affect the balance between strength and ductility of the Al/Cu joint.

Given that evaluating suspected child maltreatment is a challenging task, we aimed to begin to explore how laboratory test results may assist in its detection. Hence, we have examined biomarker differences between 137 children entering out-of-home care and 126 children living in their own homes. Each child entering Majorcan institutionalized care was randomly matched for gender and age with children living in their homes and the same health area. Concerning basic hematological and biochemical values, children placed in out-of-home care differed significantly from children remaining at home in four distinct ways. Children at care entry had significantly higher eosinophil counts than children at home; and also had significantly lower levels of transaminase, thyroid-stimulating hormone, triglycerides and LDL-Cholesterol than children living at home. Oxidative stress linked to anxiety disorders and underweight are common features found in children at entry into the care system. The present study shows a relationship between some underweight or oxidative stress biomarkers and the risk of entry into out-of-home care. Medical diagnoses require physicians to select and assemble relevant data from all available information. Accordingly, we should consider the implementation of laboratory checkups in order to identify the abused from the non-abused child better.

The fate of critically sick patients with infections in intensive care units (ICUs) is significantly influenced by antimicrobial resistance, which has become a serious concern in developing nations. This observational study was conducted at the IBN Sina Specialised Hospital in Dhaka, Bangladesh, over a 12-month period from January 2021 to December 2021, in order to track the pattern of antibiotic resistance among the patients admitted to the intensive care unit (ICU). Aspiration pneumonia (29%) and diabetes mellitus (24%), among 200 patients, were the most common main diagnoses. 65 samples (or 26%) of the 250 samples had 85 bacteria identified from them. Urine (14.12%) and tracheal aspirate (64.71%) were the most frequently found sites of infection. In the sample from the tracheal aspirate, Pseudomonas spp. (30.59%), Escherichia coli (24.71%), Acinetobacter spp. (20%), and Klebsiella spp. (14.12) were the most frequently isolated microorganisms. The following antibiotics were shown to have the highest overall patterns of resistance: levofloxacin (68.24), amikacin (64.71), meropenem (49.41), ceftazidime (75.29), ciprofloxacin (78.82), and gentamicin (82.35). The most effective antibiotic against Klebsiella species was meropenem (64.61%), while Acinetobacter species were mostly susceptible to cotrimoxazole (64.67%) and piperacillin + tazobactam (60.50%). Most susceptible to netilmicin (70.48%) and meropenem (49.32%) were Escherichia coli, while Pseudomonas spp. were mostly responsive to colistin (55.14%) and netilmicin (52.25%). Antibiotic resistance is common among intensive care unit (ICU) patients, and most isolated microbes have resistance to traditional medicines.

Chemo-resistance is a substantial challenge in the realm of cancer treatment that requires exploring new therapeutic approaches for effective mitigation. Achieving this goal requires examination of the molecular mechanisms involved in both tumor growth and therapeutic interventions. The potential of NRF2 (Nuclear factor E2-related factor 2) in addressing resistance to chemotherapy across diverse cancer types highlights its value as a promising therapeutic approach based on cancer characteristics. Manipulating the NRF2 signaling pathway has a dual impact, offering promise for both preventing and treating cancer, as well as inhibiting carcinogenesis. The influence of the NRF2/KEAP1 pathway on the progression of tumor formation and resistance to drugs has been well-documented. The interplay between the NRF2 signaling pathway and processes such as endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and autophagy plays a crucial protective role. A deeper understanding of NRF2's role in the modulating these pathways is necessary to develop novel approaches for improving chemotherapeutic efficacy. This article discusses the significance of the NRF2-KEAP1 pathway in preventing/promoting cancer and resistance mechanisms to various chemotherapeutic agents, with a focus on the complementary effects of antioxidants via NRF2-mediated signaling pathways. This study aims to provide a molecular basis for targeting NRF2 via inhibitors/activators as promising therapeutic strategies to overcome chemo-resistance.

Objective The aim of this study was to examine the impact of a modern lifestyle on college female students' health, specifically focusing on their hip and knee joint mobility. The objective of this study was to assess the influence of hydraulic resistance training with the self-myofascial release technique on improving joint mobility in female college students. The training also aimed to compare the effectiveness of hydraulic resistance exercise with and without the self-myofascial release technique on hip and knee joint mobility.Methods The study used a randomized controlled trial design to recruit 30 female college students aged 18-25 through campus advertisements and announcements. Medical conditions or injuries that might have affected participation was screened. Participants were indiscriminately allocated to Group A (Hydraulic Resistance Training with Self-Myofascial Technique) or Group B (Hydraulic Resistance Training without Self-Myofascial Technique). The baseline assessments included joint range of motion (ROM) measurements using a goniometer. Certified trainers supervised the training sessions, and the data were analyzed using SD and mean using SPSS. ResultsThis study aimed to evaluate the impact of hydraulic resistance training with self-myofascial release on hip and knee joint mobility in female college students. The results showed that both groups showed improved hip and knee flexion with and without the self-myofascial release technique. However, the Group A using the self-myofascial release technique (Group A) showed a more significant enhancement, as indicated by the smaller p value compared to Group B. It has been suggested that the self-myofascial release technique may improve hip and knee joint mobility. ConclusionThis study concluded that Hydraulic Resistance Training with Self-Myofascial Release (HSMR) could improve hip and knee joint mobility among female college students. These findings suggest that integrating the self-myofascial release technique into training regimens can improve joint mobility. However, further research with larger sample sizes and extended intervention periods was needed to understand the long-term effects and sustainability of these improvements.

Lodging poses a significant challenge to rice yield, prompting the need to identify elite alleles for lodging resistance traits to improve cultivated rice varieties. In this study, a natural population of 518 rice accessions was examined to identify elite alleles associated with plant height (PH), stem diameter (SD), stem anti-thrust (AT/S), and various internode lengths: (first (FirINL), second (SecINL), third (ThirINL), fourth (ForINL), and fifth (FifINL) internode lengths). 262 SSR markers linked to these traits were uncovered through association mapping in two environmental conditions. Phenotypic evaluations revealed striking differences among cultivars, and genetic diversity assessments showed polymorphisms across the accessions. Favorable alleles were identified for PH, SD, AT/S, and 1 to 5 internode lengths, with specific alleles displaying considerable effects. Noteworthy alleles include RM6811-160 bp on chromosome 6 (which reduces PH) and RM161-145 bp on chromosome 5 (which increases SD). The study identified a total of 42 novel QTLs. Specifically, seven QTLs were identified for PH, four for SD, five for AT/S, five for FirINL, six for SecINL, five for ThirINL, six for ForINL, and four for FifINL. QTLs qAT/S-2, qPH2.1, qForINL2.1, and qFifINL exhibited the most significant phenotypic variance (PVE) of 3.99% for the stem lodging trait. AT/S, PH, ForINL and FifINL had additive effects of 5.31 kPa, 5.42 cm, 4.27cm and 4.27cm, respectively, offering insights into eight distinct cross-combinations for enhancing each trait. This research suggests the potential for cross-breeding superior parents based on stacked alleles, promising improved rice cultivars with enhanced lodging resistance to meet market demands.

Rapid urbanization has led to many ecological problems such as landscape fragmentation, decreased landscape connectivity, and decreased biodiversity. Building an ecological security pattern is an important way to ensure ecological security and maintain sustainable urban development. Harbin is an important large-scale city in northeastern China, and the urban central district of Harbin is used as the study area. Ecological sensitivity assessment, MSPA, gravity model, landscape connectivity assessment and MCR model were used to extract ecological source areas, ecological corridors and ecological nodes in the study area to construct and optimize the ecological security pattern. Research shows that: A total of 23 ecological source areas were identified, mainly located along the Songhua River in the central part of the study area and in the mountain forest areas within the A-cheng District in the southeastern part of the study area. 48 ecological corridors were extracted, mainly in Daowai District, A-cheng District and the eastern part of Xiangfang District. There are 8 important ecological corridors and 10 important connecting corridors. 61 ecological nodes of the first level and 65 ecological nodes of the second level were extracted. High, higher, medium, lower and low security areas were classified based on the minimum cumulative resistance surface, with the highest proportion of high ecological security areas accounting for 45.75% of the study area. 65 ecological breakpoints were extracted and restoration measures were proposed. Finally, The structure of the ecological security pattern optimization of "two axes, two belts and four areas" is proposed, and corresponding ecological management measures are put forward. The experimental system of this study can provide new ideas for the construction of ecological security patterns in other regions and provide scientific support for the ecological sustainable development of similar urban areas.

Tuberculosis (TB) continues to pose a global health challenge, exacerbated by the rise of drug-resistant strains. The development of new TB therapies is an arduous and time-consuming process. To expedite the discovery of effective treatments, computational structure-based drug re-purposing has emerged as a promising strategy. From this perspective, conditionally essential targets present a valuable opportunity, and the mycobactin biosynthesis pathway stands out as a prime example highlighting the intricate response of Mycobacterium tuberculosis (Mtb) to changes in iron availability. This study focuses on the re-purposing and revival of FDA-approved drugs (library) as potential inhibitors of MbtA, a crucial enzyme in mycobactin biosynthesis in Mtb conserved among all species of mycobacteria. Literature suggests this pathway to be associated with drug efflux pumps, which potentially contribute to drug resistance. This makes it a potential target for antitubercular drug discovery. Herein we utilized cheminformatics and structure-based drug repurposing approaches, viz., molecular docking, dynamics, and PCA analysis, to decode the intermolecular interactions and binding affinity of the FDA-reported molecules against MbtA. The virtual screening revealed ten molecules with significant binding affinities and interactions with MbtA. These drugs, originally designed for different therapeutic indications (4: antiviral, 3: anticancer, 1: CYP450 inhibitor, 1: ACE inhibitor, and 1: leukotriene antagonist), are repurposed as potential MbtA inhibitors. Furthermore, our study explores the binding modes and interactions between these drugs and MbtA, shedding light on the structural basis of their inhibitory potential. Principal component analysis highlighted significant motions in MbtA-bound ligands, emphasizing the stability of the top Protein-Ligand Complexes (PLCs). This computational approach provides a swift and cost-effective method for identifying new MbtA inhibitors, which can subsequently undergo validation through experimental assays. This streamlined process is facilitated by the fact that these compounds are already FDA-approved and have established safety and efficacy profiles. This study has the potential to lay the groundwork for addressing the urgent global health challenge at hand, specifically in the context of combating Antimicrobial Resistance (AMR) and Tuberculosis (TB).

This study investigates the contribution of nano-alumina (nA: 1-3wt.% binder) to the performance of silica fume (SF-10%) blended mortar in ternary blended mortar. The fresh (workability, setting time) and hardened properties (compressive strength and thermal resistance (300 °C for 1 h)), were examined. Nano alumina (nA) contributed positively to the consistency of SF blended mortar such that similar workability could be achieved with OPC when 3% nA was added. The initial and final setting time of 180 and 220 mins were recorded in SF blended mortar and reduced by 18.4 and 21.8%, respectively by adding 3%nA. The optimum mixture that contained 10%SF and 2%nA had 3-d and 28-d compressive strengths of 28 and 43.2 MPa. In the absence of nA, this reduced by 14.3% and 29.4% while it reduced by 25.2% and 16.7%, respectively in OPC mortar. The main products characterizing SF-nA ternary blended binder with dense microstructural density were nepheline and tobermorite. Besides, it is more susceptible to carbonation despite its superior performance in thermal resistance when compared to SF blended and OPC mortars.

Antimicrobial resistance (AMR), a serious global public health challenge, may have accelerated development during the COVID-19 pandemic because antibiotics were prescribed for COVID-19. This study aimed to assess antibiotics use before and during the pandemic and correlate the results with the rate of resistant microorganisms detected in hospitalized patients during the study period. This single centre study looked retrospectively at four years of data (2018–2021) from Royal Hospital, Muscat, Oman. The consumption rate was presented as the antibiotic consumption index, the ratio of defined daily dose (DDD) per 100 bed-days. Analyses were performed using the nonparametric test for trend across the study period. Correlation between antibiotic consumption indexes and the isolated microorganisms in the four-year study period was performed using Spearman’s rank correlation coefficient. We compared data from the pre-COVID-19 to the COVID-19 period. Though more patients were admitted pre-COVID-19 (132,828 versus 119,191 during COVID-19) more antibiotics were consumed during the pandemic; vancomycin and ceftriaxone had higher consumption during than before the pandemic (p-values 0.001 and 0.036, respectively). Vancomycin-resistant Enterococcus (VRE) and Candida. auris were detected more during the COVID-19 period with p-values of 0.026 and 0.004, respectively. Carbapenem-resistant Enterobacterales (CRE), vancomycin resistant Enterococcus spp., and C. auris were detected more often during the pandemic with p-values of 0.011, 0.002, and 0.03, respectively. Significant positive correlations between antibiotic consumption and drug resistant isolates were noted. This study confirms that the overuse of antibiotics triggers the development of bacterial resistance; our results emphasize the importance of antibiotic control.

The cultivation of Hevea brasiliensis, the primary commercial source of natural rubber, is strongly impacted by South American Leaf Blight (SALB) disease, caused by the fungus Pseudocercospora ulei. Various management strategies have been implemented, including the selection of resistant genotypes and the identification of escape zones. This study evaluated the growth, early yield, and resistance to SALB of nine Colombian elite genotypes from the ECC-100 series and IAN 873 clone (control) in a large-scale clone trial in a low SALB pressure zone in the Colombian Amazon, 2017 - 2020. Favorable early performance was evident, although there was a significant increase in the severity and sporulation of P. ulei over time, especially in the ECC 35, ECC 60, and IAN 873 genotypes. However, these scores represented a low susceptibility. Genotypes with higher resistance to SALB demonstrated greater growth and early yield compared to higher susceptible genotypes. The ECC 64, ECC 73, ECC 90, ECC 25, and ECC 29 genotypes were more desirable in low SALB pressure zones due to their higher resistance and early performance. It is important to highlight that this research contributes to the selection of new SALB-resistant Colombian genotypes of H. brasiliensis in the growth stage. Therefore, it is necessary to evaluate their productivity in the mature stage and long-term resistance to SALB, before recommending and promoting their commercial adoption in the Colombian Amazon.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

Sphingolipids play an important role in the development of diabetes both type 1 and type 2 diabetes as well as in the development of both micro- and macro-vascular complications. Several reviews have been published concerning the role of sphingolipids in diabetes but most of the emphasis has been on the possible mechanisms by which sphingolipids, mainly ceramides, contribute to the development of diabetes. Research on circulating levels of the different classes of sphingolipids in serum and in lipoproteins and their importance as biomarkers to predict not only the development of diabetes but also of its complications has only recently emerged and it is still in its infancy. This review summarizes the previously published literature concerning sphingolipid-mediated mechanisms involved in the development of diabetes and its complications focusing on how circulating plasma sphingolipid levels and the relative content carried by the different lipoproteins may impact their role as possible biomarkers both in the development of diabetes and mainly in the development of diabetic complications. Further studies in this field may open new therapeutic avenues to prevent or arrest/reduce both the development of diabetes and progression of its complications.

Rather high speed of modern water bikes that they develop using only human muscle power increases their popularity. For example, the maximum speed of prototypes reaches the value 3 m/s. Similar vehicles can be used not only for recreation and fitness, but also for transportation. To increase their speed and tonnage, we recommend improving the pontoon shape and using electrical power. The total drag and maximal speeds of the vehicles with the human muscle and electrical power are estimated. Expected success in improving the pontoon shape opens wide prospects for the use of these special shaped hulls in shipbuilding.

A total of thirty-two aerobic spore former strains were isolated from intestinal samples of healthy children and analyzed for their hemolytic and antibiotic-resistance activities. Four strains selected as non-hemolytic and sensitive to all antibiotics recommended as relevant by regulatory agencies were short-listed and evaluated for their in silico and in vitro probiotic potentials. The four selected strains were assigned to the Bacillus velenzensis (MV4 and MV11), B. subtilis (MV24) and Priestia megaterium (formerly Bacillus megaterium) (MV30) species. A genomic analysis indicated that MV4, MV11 and MV24 contained a homolog of the gene coding for the fibrinolytic enzyme nattokinase while only MV30 encoded for a glutamic acid decarboxylase essential to synthesize the neurotransmitter GABA. All four strains showed a strong antioxidant activity, formed biofilm and produced/secreted quorum sensing peptides able to induce a cytoprotective stress response in a model of human intestinal (HT29) cells. Altogether, genomic and physiological data indicate that the analyzed strains do not pose safety concerns and have in vitro probiotic potentials.

Background and objective: Acinetobacter baumannii (A. baumannii) is an important nosocomial pathogen that possesses not only intrinsic resistance to many classes of antibiotics, but also is capable to rapidly develop antimicrobial resistance during treatment. The aim of our study was to determine the production of different types of β-lactamases (AmpC, ESBL, KPC) in A. baumannii strains, to evaluate its association with antimicrobial resistance, and to identify the changes in these characteristics after 5 years. Materials and methods: A total of 233 A. baumannii strains were isolated from different clinical specimens of patients treated at the Hospital of Lithuanian University of Health Sciences in 2016–2017 and 2021–2022. All clinical cultures positive for A. baumannii were analyzed. The type of β-lactamase was detected by phenotypic methods using ESBL plus AmpC screen disk tests and the combination meropenem disk test. Results: In 2016–2017 and 2021–2022, all A. baumannii strains were resistant to ciprofloxacin; more than 80% were resistant to carbapenems, piperacillin/tazobactam, gentamicin, and tobramycin. Comparison of two different period showed that the production of two different types of β-lactamases increased more than 5-fold (from 17.7% to 94.2%, p < 0.001), and the production of all three types of β-lactamases, more than 4-fold (from 1.3% to 5.8%, p < 0.001). A. baumannii strains producing two or three types of β-lactamases were more often resistant to tigecycline, tetracycline, and doxycycline than strains producing one type of β-lactamases (p < 0.001). Conclusions: The frequency of isolation of A. baumannii strains producing two or three β-lactamases types and the resistance rates to ampicillin/sulbactam, tigecycline, tetracycline, and doxycycline increased in 2020–2021 as compared with 2016–2017. The production of two or three types of β-lactamases by A. baumannii strains was associated with higher resistance rates to tetracyclines.

The method of micro-arc oxidation has been utilized to synthesize a protective biocompatible coating for a bioresorbable orthopedic Mg implant. This paper presents the results of a comprehensive research of micro-arc coatings based on diatomite – a biogenic material consisting of shells of diatom microalgae. The main focus of this study was the functionalization of diatomite-based micro-arc coatings by incorporating the particles of titania (TiO2) into them. Various properties of the resulting coatings were examined and evaluated. The XRD analysis has revealed the formation of a new magnesium orthosilicate phase – forsterite (Mg2SiO4). It has been established that the corrosion current density of the coatings has decreased by 2-4 orders of magnitude after the inclusion of TiO2 particles, depending on the coating process voltage. The adhesion strength of the coatings has increased following the particle incorporation. The processes of dissolution of both coated and uncoated samples in a sodium chloride solution were studied. The in vitro cell viability was assessed, which showed that the coatings significantly reduce the cytotoxicity of Mg samples.

The use of anti-microbial drugs and coccidiostats in poultry farming is widespread, with a significant proportion of these drugs being excreted and released into the environment. The residues of such drugs in poultry litter (PL) can result in the development of antibiotic-resistant bacteria. The impact of different biotic treatments (aerobic, anaerobic, and stacking) on broiler litter (BL) before use as animal feed has not been studied extensively, nor have the differences between antimicrobial-dependent and independent broiler farms been investigated. This study aimed to determine the resistant bacteria in BL used as ruminant feed before and after litter treatment. The results showed that the most resistant bacteria before BL treatment were Enterococcus species. The study also found that the quantity of amoxicillin-resistant Enterococcus detected in samples from antimicrobial-dependent farms was significantly higher than in those from antimicrobial-independent farms. Additionally, 14% of bacteria were multi-resistant to tetracycline, sulfafurazole, and erythromycin in antimicrobial-independent farm litters, significantly lower than those measured in antimicrobial-dependent broiler farm litter. This study highlights the importance of better understanding, regulating, managing, and using animal waste appropriately to reduce the number of antibiotic-resistant bacteria and minimize the use of antimicrobials that carry high risks for animals, humans, and the environment

The objective of this study was to compare the pathogens and susceptibilities of the current automated rule-based technology (RBT) antibiogram with one manually collected through chart review with additional rules applied. This study was a 2-year, retrospective cohort study and included all bacterial cultures within the first 30 days from patients admitted to a single Burn Center. The current RBT antibiogram served as the control and new antibiogram versions were created using additional rules and compared to the control. Six-hundred fifty-seven patients were admitted (61% excluded for lack of cultures). Fifty-nine percent had at least one hospital acquired risk factor with over one-third having recent illicit drug use and one-third having a recent hospitalization. Of the 410 cultures included, 57% were Gram-negative and half were from wound infections. Sensitivities were significantly different when comparing manual and the RBT version after including factors, such as days since admission, presence of hospital acquired risk factors, or previous antibiotic courses. Recommended empiric Gram-negative antibiotics changed from double coverage to a single β-lactam with > 90% susceptibility. The susceptibilities between first and subsequent courses were dramatically different. Before developing an antibiogram or interpreting the output, it is important to consider which automated criteria are utilized, especially for units with extended lengths of stay.

The paper investigates the influence of ion nitriding on the microstructure, corrosion resistance, and tensile strength at elevated temperatures of Haynes 282 nickel superalloy specimens produced by the Direct Metal Laser Sintering-DMLS technique. Analysis of the specimens’ surface morphology revealed that the ion nitriding process significantly affects the physical and chemical phenomena occurring on the surface of the specimens. Phase composition and stress analysis showed that Haynes 282 nickel alloy specimens produced by the DMLS technique and a chromium nitride layer produced in the ion nitriding process have tensile stress. The layer is also characterized by high nanohardness compared to specimens produced using the classical method (wrought) and DMLS technique. The conducted corrosion resistance tests confirmed the positive effect of the nitrided layer on the corrosion resistance of Haynes 282 nickel alloy produced by the DMLS technique. The ion nitriding process did not significantly affect the elevated-temperature tensile strength of Haynes 282 nickel alloy specimens produced by the DMLS technique.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations and the protracted course the infections may take, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in near future.

In a power plant that uses seawater as a coolant, a debris filter is required to remove foreign substances from the seawater, and differential pressure leads to a decrease in the coolant flow rate, leading to a decrease in power generation efficiency. In this study, analysis was performed under different initial flow velocity conditions of 1.5m/s, 2.0m/s, and 2.5m/s for a debris filter used in a power plant to understand flow characteristics in CTCS. The flow and differential pressure characteristics of a CTCS with an installed debris filter were considered in a comparative analysis of velocity, pressure, and turbulent kinetic energy distribution. The results confirmed that a vortex was generated in the pipe with the debris filter, apparently due to the collision of the flow with the bracket of the debris filter. As the flow rate increased, the range of the vortex increased, causing a loss in flow.

This study was aimed to examine the recent trends of antibiotic resistance (AR) prevalence in Staphylococcus aureus isolated from milk of animals with clinical mastitis in areas of the Abruzzo and Molise regions in central Italy. Fifty-four S. aureus isolates could be obtained from routine testing for clinical mastitis agents carried out in the author institution in years 2021 and 2022. These were analyzed for phenotypic resistance to eight antibiotics recommended for testing by European norms and belonging to the antibiotic classes used for mastitis treatment in milk producing animals. Moreover, the presence of 14 transferable genetic determinants encoding resistance to the same antibiotics was analyzed by qPCR tests developed in this study. Phenotypic resistance to non-β-lactams was infrequent, with only one 2022 isolate resistant to clindamycin. However, low level resistance to the β-lactam cefoxitin was observed in 59.2% isolates in both years making these isolates classifiable as methicillin resistant. The AR genotypes detected were blaZ gene (50% 2021 isolates and 44.4% 2022 isolates), ermC/T- aphA3-blaZ (one 2021 isolate), ant6-ermC/T-aphA3-blaZ (one 2021 isolate), ermB-blaZ (one 2022 isolate) and mecA-mph (one 2022 isolate). An interview to the veterinarians who conferred the samples, regarding antimicrobials prescribed for mastitis treatment and criteria of usage, indicated a possible causal relation with the AR test results. The low prevalence of AR genotypes, not increasing in time, most probably reflecting the reported management of antibiotic therapies in farms. However, the frequently observed cefoxitin resistance needs to be explained genotypically, further monitored and limited by modifying antibiotic usage practices. The identification of a mecA positive isolate in 2022 suggests to investigate further if this genotype is emerging locally.

Obesity is linked to an inflammatory process, with adipocyte release triggering insulin resistance (IR) and autonomic imbalance. A cardiovagal trainning protocol has shown favorable results in autonomic balance and decrease of inflammatory markers. The aim of this study was to analyze the autonomic behavior related to inflammatory and metabolic parameters in obese people after a cardiovagal exercise protocol. Twenty people with obesity, were distributed by their HOMA-IR value: obese without IR (n/IR) (n=8) and obese with IR (y/IR) (n=12). The cardiovagal training program was carried out in both groups for 8 weeks at a frequency of 5 times per week. A blood sample was obtained to determine insulin, leptin, TNF alpha and IL6 levels, in addition to determining the HOMA-IR index and autonomic function was measured by heart rate variability. Changes were recorded in the OB-IR group, a decrease in inflammatory markers, glycemia and a reduction of sympathetic activity after the cardiovagal training intervention. In addition, significant differences between the y/IR and n/IR groups were shown in insulin, leptin, TNFa and IL6 values. It can be concluded that after 4 weeks of intervention with a cardiovagal trainning protocol, parasympathetic modulation increased and inflammatory markers decreased in obese subjects.

The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

Dielectric spectroscopy (DS) is a promising cell screening method that can be used for diagnostic and drug discovery purposes. The primary challenge of using DS in physiological buffers is the electrode polarization (EP) that overwhelms the impedance signal within a large frequency range. These effects further amplify with miniaturization of the measurement electrodes. In this study, we present a microfluidic system and the associated equivalent circuit models for real-time measurements of cell membrane capacitance and cytoplasm resistance in physiological buffers with 10s increments. The current device captures several hundreds of biological cells in individual microwells through gravitational settling and measures the system’s impedance using microelectrodes covered with dendritic gold nanostructures. Using PC-3 cells (a highly metastatic prostate cancer cell line) suspended in cell growth media (CGM), we demonstrate stable measurements of cell membrane capacitance and cytoplasm resistance in the device for over 15 minutes. We also describe a consistent application of the equivalent circuit model, starting from the reference measurements used to determine the system parameters. The circuit model is tested using devices with varying dimensions, and the obtained cell parameters between different devices are nearly identical. Further analyses of the impedance data have shown that accurate cell membrane capacitance and cytoplasm resistance can be extracted using a limited number of measurements in the 5 MHz to 10 MHz range. This will potentially reduce the timescale required for real-time DS measurements below 1s. Overall the new microfluidic device can be used for dielectric characterization of biological cells in physiological buffers for various cell screening applications.

The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here we investigated how different biocides affected the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides including alcohols, hydrogen peroxide, quaternary ammonium compounds, and polymeric guanidines were evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA-PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after four weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain which demonstrates the potential of PHMG-Cl as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings.

In recent years, there is a growing concern about the alarming spread of antimicrobial resistance (AMR) in different environments. Increasingly, many species of bacteria, fungi and viruses are becoming immune to the most commonly used pharmaceuticals. One of the causes of the development of the resistance is the persistence of these drugs, excreted by humans, in municipal and hospital wastewater (WW). Consequently, wastewater treatment plants (WWTPs) are a primary source of antimicrobial resistance genes as novel pollutants. This systematic review sought to examine the relevant literature on pharmaceutical residues (PRs) responsible for AMR in municipal and hospital WW in order to propose a classification of the PRs of greatest concern and provide an updated source for AMR management in WWTPs. Among 546 studies collected from four databases, 18 were included in the present review. The internal and external validity of each study was assessed, and the risk of bias was evaluated on a 20-parameter basis. Results were combined in a narrative synthesis discussing influents and effluents PR concentrations at 88 WWTPs, seasonal variations, differences between hospital and municipal WW, environmental risk assessment values of antimicrobial substances and treatment facilities removal efficiencies. Among the 45 PRs responsible for AMR evaluated in this study, the antibiotics ciprofloxacin, clarithromycin, erythromycin, metronidazole, ofloxacin, sulfamethoxazole and trimethoprim constitute a considerable risk in terms of ubiquitous distribution, worrying concentrations, risk quotients values, and resistance to removal treatments. Gaps in knowledge, data and information reported in this review provide a valuable source for managing AMR in WWTPs.

ANGPTL3 is an important regulator of lipid metabolism. Its inhibition in people with hypercholesteremia reduces plasma lipid levels dramatically. Genome-wide association studies have associated ANGPTL3 variants with lipid traits. Irisin, an exercise modulated protein, has been associated with lipid metabolism. Intracellular accumulation of lipids impairs insulin action and contributes to metabolic disorders. In this study, we evaluate the impact of ANGPTL3 variants on levels of irisin and markers associated with lipid metabolism and insulin resistance. ANGPTL3 rs1748197 and rs12130333 variants were genotyped in a cohort of 278 Arab individuals from Kuwait. Levels of irisin and other metabolic markers were measured by ELISA. Significance of association signals was assessed using Bonferroni-corrected P-values and empirical P-values. The study variants were significantly associated with low levels of c-peptide and irisin. Levels of c-peptide and irisin were mediated by interaction between carrier genotypes (GA+AA) at rs1748197 and measures of IL13 and TG, respectively. While levels of c-peptide and IL13 were directly correlated in individuals with reference genotype, they were inversely correlated in individuals with carrier genotype. Irisin correlated positively with TG which is strong in individuals with carrier genotypes. These observations illustrate ANGPTL3 as a potential link connecting lipid metabolism, insulin resistance and cardioprotection.

Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies de-scribing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonautes proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases and an atypical ribonuclease III (RNaseIII). NCRIP regulates the expression of mRNAs by degrading them in a specific manner. Its mechanism binds dsRNA but only cuts ssRNA. NCRIP exhibits a diversity of functional roles. It represses the epimutational pathway and the lack of NCRIP increases the generation of drug resistant strains. NCRIP also regulates the control of retrotransposons expression, playing an essential role in genome stability. Finally, NCRIP regulates the response during phagocytosis, affecting the multifactorial process of virulence. These critical NCRIP roles in virulence and antifungal drug resistance, along with its exclusive presence in Mucorales, mark this pathway as a promising target to fight against mucormycosis.

Wound infections evidently appeared in times of World War I that accounted a significant mortality and morbidity rate among injured soldiers. Currently, around 11 million people worldwide require medical treatment for wound infections and 300,000 die every year due to untreated wound infection. The extensive use of antibiotics to treat wound infection leads to emerging new microbial strains that are resistant to many antibiotics. There is a growing concern on the emergence and re-emergence of drug-resistant pathogens such as multi-resistant bacterial strains. Hence, the development of new antimicrobial compounds or the modification of those that already exist to improve antibacterial activity is a high priority area of research. During the past few decades, nanotechnology has arisen with new promising technology for synthesis of nanobiomaterials. Metallic nanoparticles (NPs) are considered as new alternative treatment with superior antibacterial activity. In this study, new formulation of titanium oxide (TiO2) NPs with different sizes were synthesized and characterized. Genotoxicity, mutagenicity and antibacterial activities of TiO2 NPs against the causative agents of wound infection were investigated. Antibacterial activity of TiO2 NPs was conducted against three ATCC ® bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. The results clearly illustrate a superior antibacterial activity of all newly formulated TiO2 NPs against the most causative agents of wound infection. Most of our TiO2 NPs showed non-genotoxic and non-mutagenic results at the maximum concentrations. Findings of this study will enhance the future of the therapeutic strategies against the resistant pathogenic strains that cause wound infections.

Background: In the present study, cisplatin, artemisinin and oleanolic acid were evaluated alone and in combination, on human ovarian A2780, A2780ZD0473R and A2780cisR cancer cell lines with aim of overcoming cisplatin resistance and side effects. Methods: Cytotoxicity was assessed by MTT reduction assay. CI values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Results: Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism and biosynthetic processes and drug resistance and detoxification. Conclusion: Results indicate that appropriately sequenced combinations of cisplatin with ART and OA may provide a means to reduce side effects and circumvent platinum resistance.

To address the severe distresses of asphalt pavement, a new type of pavement maintenance treatment, porous ultra-thin overlay (PUTO) with small particle size was proposed. The PUTO has a thickness of 1.5~2.5 cm and a large void ratio of 18~25%. As a newly asphalt mixture, the structure characteristics differ from traditional pavement. Therefore, it is necessary to investigated the fabrication schemes in laboratory and on-site, respectively. In this study, the optimal fabrication schemes, including compaction temperature and number of blows of PUTO were determined based on Cantabro test and volumetric parameters. Then, the corresponding relationship between laboratory and on-site compaction work was then established based on the energy equivalent principle. On this basis, the numbers of on-site rolling passes and the combination method were calculated. The results show that increased compaction temperature and number of blows reduce the height and enhance the compactness of the Marshall sample. With the same temperature and number of blows, the scattering resistance of coarse gradation (PAC-1) is better than that of fine gradation (PAC-2), and the increased asphalt viscosity significantly improves the scattering resistance of the asphalt mixture. To ensure the scattering resistance and volumetric characteristic, the initial compaction temperature of the PAC-1 and PAC-2 should not be lower than 150 °C and 165 °C, respectively. Then, the laboratory compaction work and on-site compaction work were calculated and converted based on the principle of energy equivalence. Consequently, the on-site compaction combination of rolling machines for four asphalt mixtures was determined. According to the volumetric parameters, the paving test section proved that the construction temperature and the on-site rolling combination determined by laboratory tests are reasonable, and ultra-thin overlay has good structural stability, drainage and skid resistance.

Angiogenesis is a term that describes the formation of new blood and lymphatic vessels from a pre-existing vasculature. This allows tumour cells to acquire sustenance in the form of nutrients and oxygen and the ability to evacuate metabolic waste. As one of the hallmarks of cancer, angiogenesis has been studied extensively in animal and human models to enable better understanding of cancer biology and the development of new anti-cancer treatments. Angiogenesis plays a crucial role in the process of tumour genesis, because solid tumour need a blood supply if they are to grow beyond a few millimeters in size. On the other hand, there is growing evidence that some solid tumour exploit existing normal blood supply and do not require a new vessel formation to grow and to undergo metastasis. This review of the literature will present the current understanding of this intricate process and the latest advances in the use of angiogenesis-targeting therapies in the fight against cancer.

This study is focused on the experimental investigation of compressive strength and durability properties of lightweight concrete mixtures with fine expanded glass and expanded clay aggregates using different microfillers. The paper proposes the relationships between the compressive strength and density of concrete mixtures with different proportions of lightweight aggregates mentioned above. The performed experimental studies have revealed the tendencies of possible usage of different amount of fine lightweight aggregates and their combinations in the production of concrete mixtures depending on the demands of practical application. Following the requirements for structural concrete subjected to environmental effects, durability properties (alkaline corrosion and freeze–thaw resistance) of the selected concrete mixtures with expanded glass aggregate were studied. The results of the experimental investigations have shown that durability of tested concrete specimens was sufficient. The study has concluded that the mixtures under consideration can be applied for the production of structural elements to which durability requirements are significant.

Heavy metals are compounds that can be hazardous and impair growth of living organisms. Bacteria have evolved the capability not only to cope with heavy metals but also to detoxify polluted environments. Three heavy metal-resistant strains of Mucilaginibacer rubeus and one of Mucilaginibacter kameinonensis were isolated from the gold/copper Zijin mining site, Longyan, Fujian, China. These strains were shown to exhibit high resistance to heavy metals with minimal inhibitory concentration reaching up to 3.5 mM Cu(II), 21 mM Zn(II), 1.2 mM Cd(II), and 10.0 mM As(III). Genomes of the four strains were sequenced by Illumina. Sequence analyses revealed the presence of a high abundance of heavy metal resistance (HMR) determinants. One of the strain, M. rubeus P2, carried genes encoding 6 putative P1B-1-ATPase, 5 putative P1B-3-ATPase and 4 putative Zn(II)/Cd(II) P1B-4 type ATPase, and 16 putative RND-type metal transporter systems. Moreover, the four genomes carry a high abundance of genes coding for putative metal binding chaperones. Analysis of the close vicinity of these HMR determinants uncovered the presence of clusters of genes potentially associated with mobile genetic elements. These loci include genes coding for tyrosine recombinases (integrases) and subunits of mating pore (type 4 secretion system) respectively allowing integration/excision and conjugative transfer of numerous genomic islands. Further in silico analyses revealed that their genetic organization and gene products resemble the Bacteroides integrative and conjugative element CTnDOT. These results highlight the pivotal role of genomic islands in the acquisition and dissemination of adaptive traits, allowing for rapid adaption of bacteria and colonization of hostile environments.

Education and awareness raising are the primary tools of global health policy to change public behaviour. Considering the limitations of awareness agenda and the lack of social research to inform alternative approaches, our objective was to generate new empirical evidence on the consequences of antibiotic-related awareness raising in a low-income country context. We implemented an educational activity in two Lao villages to share general antibiotic-related messages, but also to learn about people’s conceptions and health behaviours. Two rounds of census survey data enabled us to assess the activity’s outputs, its knowledge outcomes, and its immediate behavioural impacts in a difference-in-difference design. Our panel data covered 1,130 adults over two rounds, including 58 activity participants and 208 villagers exposed indirectly via conversations in the village. We found that activity-related communication circulated among more privileged groups, which limited its indirect effects. Among participants, the activity influenced the awareness and understanding of “drug resistance,” while effects on attitudes were minor. Evidence on behavioural impacts was sparse and mixed, but the range of possible consequences included a disproportionate uptake of antibiotics from formal healthcare providers. Our study casts doubt on the continued dominance of awareness raising as a behavioural tool to address antibiotic resistance.

Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical system theory represents a high-dimensional cell state space, in which each cell phenotype is considered as an “attractor” that is determined by interactions among multiple variables (molecular players), and is buffered against environmental fluctuations. Further, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss these phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors” – hidden stable states of the underlying regulatory network that are not occupied by normal cells. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of drug/hormone resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to drug/hormone treatment. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes ‘recanalization’, i.e. the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.

The benthic matrix acts as a key natural archive where the memory of long-term timescale environmental changes is recorded. Some ecological and chemical features of fjord sediments were explored during the AREX cruise carried out in the Svalbard archipelago in summer 2021. The activity rates of the enzymes leucine aminopeptidase (LAP), beta-glucosidase (GLU) and alkaline phosphatase (AP) and community-level physiological profiles (CLPP) were studied with the aim of determining the functional diversity of the benthic microbial community, while bacterial isolates were screened for their susceptibility to antibiotic molecules in order to explore the role of these extreme environments as potential reservoirs of antibiotic resistance. Enzyme activity rates were obtained by fluorogenic substrates, CLPP by Biolog Ecoplates; antibiotic susceptibility assays were performed through the standard disk diffusion method. Spatial trends observed in the functional profiles of the microbial community suggested the variability in the microbial community composition, presumably related to the patchy distribution of organic substrates. Complex Carbon sources, carbohydrates and amino acids were the organic polymers preferentially metabolized by the microbial community. Multiple resistance to ampicillin, clindamycin and gentamycin was detected in all the sampled sediments, excepting in the southern Hornsund area, stressing the role of sediments as a potential reservoir of chemical wastes ascribable to antibiotic residuals. This study provides new insights on the health status of fjord sediments of West Spitsbergen applying a dual ecological and biochemical approach. Microbial communities in the fjord sediments showed globally a good functional diversity, suggesting their versatility to rapidly react to changing conditions.

Abstract: Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phe-notypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes with the phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reac-tions detected mcr gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilu-tion and E-test by minimal inhibitory concentration (MIC) measurements. Over 30.0% (69/225) of isolates showed colistin resistance by agar dilution assessment (MIC> 2.0 μg/mL). Overall, 15.5% of isolates carried mcr genes (7, mcr-1; 17, mcr-2; 13, mcr-3; and co-occurrence occurred in 2 isolates). Clinical breakout MIC val-ues (≥ 4 μg/mL) were associated with 91.3% of mcr-positive isolates. The mcr-positive pathogens include twenty Escherichia spp., five Shigella flexneri, five Citrobacter spp., two Klebsiella pneumoniae, and three Pseudo-monas parafulva. mcr-genes appeared to be significantly associated with phenotypic colistin resistance phe-nomena (p=0.000), with 100% colistin-resistant isolates showing MDR phenomena. Age and sex of patients showed no significant association with detected mcr variants. Overall, mcr-associated colistin-resistant bacte-ria have emerged in Bangladesh, which warrants further research to determine their spread and instigate ac-tivities to reduce resistance.

Several efforts have been made to estimate the prevalence of different types of antibiotic resistance in different regions of Nigeria. The study investigated the prevalence of Klebsiella pneumoniae encoding genes for CTX-M, TEM, and SHV-1 extended-spectrum beta-lactamases (ESBL) enzymes isolated from urine samples of non-hospitalized patients with suspected UTI in Lagos State, Nigeria. A 4-month retrospective study, spanning from May 2023 to August 2023, was conducted. K. pneumoniae was isolated from urine samples using standard microbiological methods. The modified Kirby-Bauer disc diffusion method was used to test for antibiotic susceptibility, and Clinical and Laboratory Standard Institute (CLSI) guidelines were followed for interpretation. The double-disk synergy method was used to confirm the phenotypic identity of ESBL producers, and the results were interpreted in accordance with CLSI guidelines. The phenotypic method was utilized for ESBL screening, employing the standard disk diffusion method. The CTX-M ESBL gene, TEM gene, and SHV gene were found using multiplex PCR. Results revealed that 41 K. pneumoniae isolates were resistant to third-generation Cephalosporins; the isolates showed resistance to ceftazidime in 100% of cases and ceftriaxone in 80.49% of cases respectively. It was determined that 8 (19.51%) of the isolates produced ESBL. Among Klebsiella isolates, the frequencies of the SHV, TEM, and CTX-M genes were 31 (75.61%), 4 (9.76%), and 10 (24.39%), in that order. Four isolates (9.67%) had the SHV, TEM, and CTX-M genes, while eight (19.51%) of the isolates possessed both the SHV and CTX-M genes. This investigation demonstrates high frequency, wide range of patterns and coexistence of ESBL genes in K. pneumoniae isolates from outpatient UTI patients. Although several phenotypic tests have been used for ESBL detection, testing directly for the presence of ESBL genes is always more accurate. The majority of the isolates of Klebsiella pneumoniae ESBL producers had the SHV gene identified.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

Infections caused by KPC-producing K. pneumoniae continue to pose a significant clinical challenge due to emerging resistance to new antimicrobials. We investigated the association between two drugs whose roles have been repurposed against multidrug-resistant bacteria: fosfomycin and temocillin. Temocillin exhibits unusual stability against KPC enzymes, while fosfomycin acts as a potent “synergizer”. We conducted in vitro antimicrobial activity studies on 100 clinical isolates of KPC-producing K. pneumoniae using a combination of fosfomycin and temocillin. The results demonstrated synergistic activity in 91% of the isolates. Subsequently, we assessed the effect on Galleria mellonella larvae using 5 different KPC-Kp isolates. The addition of fosfomycin to temocillin increased larvae survival from 73 to 97% (+Δ 32%; isolate 1), from 93 to 100% (+Δ 7%; isolate 2), from 63 to 86% (+Δ 36%; isolate 3), from 63 to 90% (+Δ 42%; isolate 4), and from 93 to 97% (+Δ 4%; isolate 10), respectively. Among the temocillin-resistant KPC-producing K. pneumoniae isolates (24 isolates), the addition of fosfomycin reduced temocillin MIC values below the resistance breakpoint in all isolated except one. Temocillin combined with fosfomycin emerges as a promising combination against KPC-producing K. pneumoniae, warranting further clinical evaluation.

This study investigated the presence, distribution, and antimicrobial resistance profiles of extend-ed-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in a dairy herd located in Northern Italy. A questionnaire was administered, and the feces of clinically healthy pre-weaned dairy calves, their mothers, and the cows treated for mastitis, waste milk, water, and environmental samples, were collected and inoculated on Chromagar ESBL™ medium. The questionnaire identi-fied several risk factors including administration of waste milk to male calves, lack of routine cleaning of calf feeding and housing equipment, and blanket dry cow therapy. Escherichia coli was identified by MALDI-TOF MS in the feces of 28 of 37 (75.67%) calves, 2 of 3 (66.67%) treated cows, 8 of 14 (57.15%) environmental samples, and the waste milk. Six of 14 (42.85%) environmental samples were also positive for ESBL Acinetobacter baumannii, while all fecal samples were negative. ESBL production was confirmed for all E. coli isolates based on the double disk susceptibility test (DDST), while none were carbapenemase producers. Upon minimal inhibitory concentration (MIC) analysis, all of them showed multiple resistances and were categorized as multi-drug resistant (MDR). This study confirms the widespread presence of MDR, ESBL-E. coli in dairy calves and highlights their diffusion in the farm environment.

As yin and yang, cancer and diabetes are metabolic disorders characterized by deregulated, yet opposing, metabolic alterations. These metabolic shifts reflect a complex network of defective underlying signaling pathways, which ultimately orchestrate both disease pathogenesis and progression. The Warburg effect portrays the chief metabolic phenotype in cancer and is reflected by the dominance of aerobic glycolysis over minimal-to-no viable oxidative phosphorylation in cancer. Conversely, during the pathogenesis of type 2 diabetes (T2D), oxidative phosphorylation is constantly heightened. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, with exacerbating metabolic alterations affecting oxidative phosphorylation in a tissue-specific manner. Promising nutritional adjuvants, such as alpha-lipoic acid and flavonoids, can reprogram metabolism and exert antitumor and antidiabetic effects. Other pharmacological agents, such as metformin, have therapeutic effects on cancer and T2D. Herein, we discuss the molecular mechanisms and signaling pathways involved in the metabolic shifts in cancer and T2D, and explore the therapeutic strategies under investigation that aim to reverse the metabolic shift in both disease scenarios.

The occurrence rate of occupational accidents caused by slipping and falling is 50% worldwide. Determining the slip safety risk is necessary to minimize the accidents caused by slipping in pedestrian walking areas. By on-site testing, this study aims to determine the slip risks of floor coverings used in walking areas with many pedestrians in public service buildings (PSB). For this purpose, on-site measurements were performed in two environments and six locations in PSB using portable GMG 200 and pendulum testers operating according to DIN 51131 and TS EN 14231 standards. These tests were performed on four-floor coverings with polished surface treatment in PSB. Since the floor coverings measured have a polished surface, it can be seen that the dynamic friction coefficients (DCOF) values are very low, and the slip risks are high. By statistically analyzing the slip test data using the K-means method, a new safety classification was made according to the usage areas of floor coverings. To minimize the risk of slip safety, especially for students, patients, and employees in PSB, it is recommended to use floor coverings with high DCOF values and low slip risk.

Rabson-Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We are reporting the first case of Rabson-Mendenhall syndrome in a Paraguayan patient. The patient is a 5-year-old girl who presented with hypertrichosis, acanthosis nigricans, and nephrocalcinosis. Genetic testing by NGS revealed two pathogenic variants in exons 2 and 18 of the INSR gene; c.332G&gt;T (p. Gly111Val) and c.3485C&gt;T (p. Ala1162Val), in combined heterozygosis. The novel INSR c. 332G&gt;T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software predicted it as pathogenic. The c. 3485C&gt;T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and Rabson-Mendenhall syndrome. The management of Rabson-Mendenhall syndrome is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of Rabson-Mendenhall syndrome to the Paraguayan population and adds a novel pathogenic variant to the existing literature.

Sustainable food systems imply the re-use of biowastes and water. In this paper we characterize 30 top soil improvers of anthropogenic, animal and green waste origin, and 11 irrigation waters from rivers, channels, and civil wastewater treatment plants (cWWTPs) for the presence of antimicrobials. Liquid chromatography coupled to hybrid High Resolution Mass Spectrometry (LC-HRMS/MS) was applied to determine 50 different drugs belonging to the classes of sulfonamides (11), tetracyclines (7), fluoroquinolones (10), macrolides (12), amphenicols (3), pleuromutilins (2), diaminopyrimidines (1), rifamycines (1) and lincosamides (1). Biowastes from cWWTPs and animal manure, slurry and litter revealed the highest loads for sulfonamides, tetracyclines, fluoroquinolones, and macrolides (80, 470, 885, and 4,487 ng/g wet weight, respectively) with nor- and cipro-floxacin as marker of anthropogenic sources. In composts and digestates antimicrobials were almost below the determination limits. Re-used waters for irrigation in open field lettuce production resulted contaminated in the range of 12-221 ng/L for sulfonamides, tetracyclines, and fluoroquinolones, against very few detects in channels and surface waters. Antimicrobials Hazard Index (HI) based on Predicted No Effect Concentration for Antimicrobial Resistance (PNEC_AMR) was largely >100 in contaminated top soil improvers from urban and animal sources. Accounting for worst-case inputs from top soil improvers and irrigation water and dilution factors of amended soil, fluoroquinolones only showed a HI around 1 in open fields for lettuce production. The origin of top soil improvers plays a pivotal role for safe and sustainable leafy vegetable productions, to abate the risk of AMR onset in food-borne diseases, as well the transfer of AMR elements to human gut flora.

One of the key pathogenetic links of type 2 diabetes mellitus (T2DM) is the formation of insulin resistance (IR). Besides a wide selection of synthetic antidiabetic drugs, various plant-origin extracts are also available to support the treatment of T2DM. This study aimed to investigate and gain knowledge of the chemical composition and potential IR correction effect of American cranberry (Vaccinium macrocarpon Aiton) leaf extracts and formulate novel 3D-printed oral dosage forms for such extracts. The bioactivity and IR of L-arginine-loaded cranberry leaf extracts were studied in vivo in rats. The cranberry leaf extracts consisted of quinic, 3-caffeoylquinic (chlorogenic), p-coumaroylquinic acids, quercetin 3-O-galactoside, quercetin-3-O-glucoside, quercetin-3-xyloside, quercetin-3-O-arabino-pyranoside, quercetin-3-O-arabinofuranoside, quercetin 3-O-rhamnoside and quercetin-O-p-coumaroyl-hexoside-2 identified by HPLC. In-vivo studies with rats showed that the oral administration of the cranberry leaf extracts had a positive effect on insulin sensitivity coefficients under ITT test, and affected HOMA-IR levels and liver lipid content with experimental IR. A novel 3D-printed immediate-release dosage form was developed for the oral administration of cranberry leaf extracts using polyethylene oxide (PEO) as a carrier gel in a semi-solid extrusion (SSE) 3D printing. In conclusion, American cranberry leaf extracts loaded with L-arginine could find uses in preventing health issues associated with IR.

Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden collected between March 2022 and May 2023 were whole-genome sequenced using next-generation sequencing, mainly with the Nanopore sequencing method. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. The dominant sublineages changed over time and mutations conferring resistance to currently available mAbs became common. Notable ones are R346T and K444T mutations in the RBD that confer significant resistance against tixagevimab and cilgavimab mAbs. Further, mutations conferring a high-fold resistance to bebtelovimab, such as the K444T and V445P mutations, were also observed in the samples. This study highlights that resistance mutations have over time rendered currently available mAbs ineffective against SARS-CoV-2 in most patients. Therefore, there is a need for continued surveillance of resistance mutations and the development of new mAbs that target more conserved regions of the RBD.

Antibiotic resistance has emerged as one of the major concerns to public human health due to issues in treatment and control of major infectious diseases. From discovery of penicillin in 1940, the antibiotic resistance originated and now developed the microorganisms as resistive strains to the major available antibiotics. Furthermore, studies on this captivating activity of the microbes provide insight into the complexities of microbial physiology and may offer some guidance in preventing the onset and consequent development of antibiotic resistance. Despite of initiatives taken in last few decades to overcome the issues, the trends of antibiotic resistance gained much peak. Antibiotic resistance appears to have emerged as a result of various factors including antibiotics being misused and overused in both the medical field and the agricultural sector. Important factors in the development of antibiotic resistance also include bacterial mutation, unplanned evolution, and horizontal gene transfers. In addition, antibiotics resistance imposed the financial consequences to public health and drug development research. Future advancements related to innovative antibiotics and molecular drug designing become challenge for researchers due to intensive multiple antibiotics resistance among human population. Many researches have been conducted on origin, evolutionary aspect of antibiotic resistance and mechanisms of antibiotics resistance, but its effect on future drug development is little understood. Therefore, the recent review will highlight the role of antibiotic resistance in drug designing and impacts of antibiotic resistance on drug development in future.

(1) Background: The emergence of antibiotic-resistant bacteria is a growing concern in the field of medicine. This has led to the need for alternative treatments for bacterial infections. (2) Methods: The present study aimed to investigate the synergistic effect of a water-based extract of S. fru-tescens and penicillin G on the growth of E. faecalis. (3) Results: The study found that the combina-tion of the plant extract and penicillin G had a synergistic effect on the inhibition of bacterial growth, with a significantly larger inhibition zone observed compared to penicillin G alone. The MIC and MBC tests also demonstrated that the combination of the plant extract and penicillin G was more effective against E. faecalis than penicillin G alone, with a dilution of 1 in 4 yielding 100% inhibition of growth. (4) Conclusion: Although the specific mechanism of action was not dis-cussed in the study, the results suggest that the combination of the plant extract and penicillin G may offer a promising alternative treatment for antibiotic-resistant infections. Further research is needed to determine the active compounds in the plant extract and to investigate the synergistic effect of the combination on other strains of bacteria.