The paper presents an innovative hexapod walking robot built with 3-UPU parallel mechanism. In the robot, the parallel mechanism is used as both an actuator to generate walking and also a connecting body to connect two groups of three legs, thus enables the robot to walk with simple gait by very few motors. In the paper, the forward and inverse kinematics solutions are obtained. The workspace of the parallel mechanism is analyzed using limit boundary search method. The walking stability of the robot is analyzed, which yields the robot’s maximum step length. The gait planning of the hexapod walking robot is studied for walking on both flat and uneven terrains. The new robot, combining the advantages of parallel robot and walking robot, has a large carrying capacity, strong passing ability, flexible turning ability, and simple gait control for its deployment for uneven terrain.

An efficient, eco-compatible and very cheap method for the construction of triazoles via eliminative azide–olefin cycloaddition (EAOC) reaction has been developed by a catalytic system IL/FeCl3, offering an highly regioselective approach to structurally diverse 1,5-disubstituted 1,2,3-triazoles in up to 95% yield. This strategy features the reuse of catalytic system through simple operations. Mechanistic studies indicated that an asynchronous concerted dipolar cycloaddition-elimination process might be involved.

Corona loss generated from conductors is one of the important design factors on ac transmission lines. Based on helical charge simulation method, the 3-D corona loss calculation model considering the conductors’ outer strands in the corona cage is established. With regard to 2-D corona-loss calculation method, the calculation model proposed in this paper can take the electric field strength’s nonuniformity along the axial direction of stranded conductor into consideration, furthermore, it can also calculate the corona loss when the conductor has sag. The calculation results of the LGJ-300/40 and LGJ-400/35 in the small corona cage well coincide with the measurement results, which indicates that the corona-loss calculation model is appropriate. In addition, the corona loss of the bundle conductors 4 × LGJ720 with sag in UHV corona cage is also analyzed.

Aiming at the damage detection and continuous monitoring of high efficiency composite structure, the method of carbon nano sensor embeded in the 3-D braided composite material specimen was put forward and the method of damage location for 3-D braided composite material was described. In this paper, the mechanical and electrical characteristics of carbon nano-fiber were analyzed. Considering the massive data of the health monitoring of composite processing, to ensure that the system has good real-time performance, quaternary matrix Singular Value Decomposition algorithm is proposed to simplify data and improve the efficiency of the algorithm. The existence of injury is determined and the damage location is calculated by comparing with key features of healthy specimen. Experimental results prove the method is feasible and effective.

We investigate entropy generation in unsteady three-dimensional axisymmetric MHD nanofluid flow over a non-linearly stretching sheet. The flow is subject to thermal radiation and a chemical reaction. The conservation equations were solved using the spectral quasi-linearization method. The novelty of the work is in the study of entropy generation in three-dimensional axisymmetric MHD nanofluid and the choice of the spectral quasilinearization method as the solution method. The effects of Brownian motion and thermophoresis are also taken into account when the nanofluid particle volume fraction on the boundary in passively controlled. The results show that as the Hartman number increases, both the Nusselt number and the Sherwood number decrease whereas the skin friction increases. It is further shown that an increase in the thermal radiation parameter corresponds to a decrease in the Nusselt number. Moreover, entropy generation increases with the physical parameters.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients who have a thrombophilic predisposition. In this case, a female patient with no family history of thrombophilia who had pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) when she was 6 years old; 6 months after receiving a second dose of the BNT162b2 vaccine, DVT reoccurred. The original thrombi were found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. The patient was treated with anticoagulants for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine exacerbated the patient’s APS by activating coagulation, causing thrombosis recurrence. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

.Bacground: Sepsis remains a major health challenge worldwide, characterized by a dysre-gulated host response to infection, leading to high mortality and morbidity in intensive care units (ICUs). The Fibrosis 4 (FIB-4) index, originally developed to assess liver fibrosis in hepatitis C patients, has recently been explored for its potential prognostic value in sepsis patients. Method: This study retrospectively analyzed 309 sepsis patients admitted to the Internal Me-dicine and Anaesthesia ICUs between December 12, 2021, and December 15, 2023, to inves-tigate the relationship between FIB-4 levels, Acute Physiology and Chronic Health Evaluation (APACHE), and Sequential Organ Failure Assessment (SOFA) and clinical outcomes. Results: The study found that higher FIB-4 measurements were statistically significantly asso-ciated with increased 28-day mortality, with a cut-off value of 4.9 providing a sensitivity of 54.92% and specificity of 74.25%. Logistic regression analysis indicated that elevated Conclusion:FIB-4 levels were a significant predictor of early mortality, suggesting that the FIB-4 index could serve as a valuable prognostic tool in assessing the severity and prognosis of sepsis patients.

Endothelial function is regulated by a myriad of complex pathways. In our previous study, the expression of miR-378a-3p was shown to inhibit endothelial autophagy and impair endothelial function. However, the mechanism underlying the effect of miR-378a-3p in endothelial cells remains to be elucidated. By employing an in silico approach, Protein Disulfide Isomerase 4 (PDIA-4) was identified as a target of miR-378-3p; however, its’ role in endothelial cells is not known. We here report that endothelial cell-specific loss of PDIA-4 leads to impaired autophagic flux accompanied by loss of endothelial function and apoptosis. Endothelial cell-specific loss of PDIA-4 also induced marked changes in endothelial cells’ architecture, accompanied with the loss of endothelial markers and gain of mesenchymal markers consistent with endothelial-to-mesenchymal transition (EndMT). Loss of PDIA-4 activates TGF-signaling, and inhibition of TGF-signaling inhibits EndMT in PDIA-4 silenced endothelial cells in vitro. Our findings help elucidate the role of PDIA-4 in endothelial autophagy and endothelial function and provide a potential target to modulate and/or limit autophagy and EndMT in (patho-)physiological conditions.

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a-f) with a protonated endocyclic nitrogen atom and then heterocyclic salts (3a-j) containing a 4-imidazoline ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a-j towards hydrolysis and alcoholysis makes them excellent candidates for the search of new types of biologically active compounds.

The rapid progress in artificial intelligence, machine learning, and natural language processing has led to the emergence of increasingly sophisticated large language models (LLMs) enabling their use in healthcare. The study assesses the performance of two LLMs: the GPT-3.5 and GPT-4 models in passing the medical examination for access to medical specialist training in Spain MIR. Our objectives included gauging the model's overall performance, analyzing discrepancies across different medical specialties, discerning between theoretical and practical questions, estimating error proportions, and assessing the hypothetical severity of errors committed by a physician. We studied the 2022 Spanish MIR examination after excluding those questions requiring image evaluations or having acknowledged errors. The remaining 182 questions were presented to the LLM ChatGPT4 and GPT-3.5 in Spanish and English. Logistic regression models analyzed the relationships between question length and question sequence d performance. GPT-4 outperformed GPT -3.5, scoring 86.81% in Spanish (p<0.001). English translations had a slightly enhanced performance. Among medical specialties, GPT-4 achieved a 100% correct response rate in several areas, with specialties like Pharmacology, ICU, and Infectious Diseases showing lower performance. The error analysis revealed that while a 13.2% error rate existed, gravest categories like "error requiring intervention to sustain life" and "error resulting in death" had a 0% rate. Conclusions: GPT-4 performs robustly on the Spanish MIR examination, varying its capability to discriminate knoweldge across specialties. While the model's high success rate is commendable, understanding the error severity is critical, especially when considering AI's potential role in real-world medical practice and its implication on patient safety.

Top-down models are defined by hardware architects to provide information on the utilization of the different hardware components. The target is to isolate the users from the complexity of the hardware architecture while giving them insight into how efficiently the code is using the resources. In this paper, we explore the applicability of 4 top-down models defined for different hardware architectures powering state-of-the-art HPC clusters (Intel Skylake, Fujitsu A64FX, IBM Power9, and Huawei Kunpeng 920) and propose a model for AMD Zen 2. We study a parallel CFD code used for scientific production to compare these 5 Top-Down models. We evaluate the level of insight achieved, the clarity of the information, the ease of use, and the conclusions that each one allows us to reach.

Plasmodium species that cause malaria, a disease responsible for about half a million deaths per annum despite concerted efforts to combat it. The causative agent depends on type III beta phosphatidylinositol 4-kinase (PPI4K) during the development of merozoite. PPI4K is the only clinically validated Plasmodium kinase so far and its inhibitors are effective both in vitro and in vivo. In this work, a small library of ~22 000 fragments was virtually screened using PPI4K homology model to discover potential ligands of the enzyme. 16 virtual hits were selected based on ≤ -9.0 kcal/mol binding energy cut off and were subjected to similarity and substructure searching after they had passed PAINS screening. The derivatives obtained showed improved binding energies, which ranged from -10.00 to -13.80 kcal/mol. Moreover, the topmost ranking compound 31, with interesting drug-like quality was stable within the protein’s binding cavity during the 10 ns molecular dynamics simulation period. In addition, analysis of its binding pose revealed some unique binding interactions with PPI4K active site residues as the basis for the observed improved binding affinity. Overall, compound 31 appears to be a viable starting point for the development of PPI4K inhibitors with antimalarial activity.

Background: Recent researches have investigated the biological importance of RNA N1-methyladenosine (m1A) modifications in oncogenesis and progression of head and neck squamous cell carcinoma (HNSCC). However, whether m1A modifications also have latent effect in tumor microenvironment (TME) generation and immune regulation in HNSCC is unknown. Methods: We evaluated the m1A modification patterns and related to these modification patterns with TME cell infiltration features in 1041 HNSCC samples by bioinformatics approach. Results: The m1A score is an independent prognostic indicator. HNSCC patients with low m1A score group with poor overall survival (OS) was mainly characterized by stroma activation, lack of sufficient immune infiltration, and exhibited an immune- desert TME phenotype. Low m1A scores were also correlated with increased tumor mutation burden (TMB), and HNSCC patients with high TMB and low m1A scores had the worst OS. In addition, anti-CTLA-4 combined with anti-PD1 treatment was more effective in the high m1A score subgroup than in the low m1A score subgroup. Conclusions: This study revealed that m1A modifications play a non-negligible role in developing the TME versatility and complexity of HNSCC. Assessing m1A modification patterns in HNSCC helps improve our comprehension of its TME infiltration profile and guides more effective immunotherapeutic approaches.

Hepatitis B virus (HBV) infection is a major factor in development of various liver diseases such as hepatocellular carcinoma (HCC). Among HBV encoded proteins, HBV X protein (HBx) is known to play key role in development of HCC. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear transcription factor which is critical for hepatocyte differentiation. However, the expression level as well as its regulatory mechanism in HBV infection have yet to be clarified. Here, we observed the suppression of HNF4α in cells which stably express HBV whole genome or HBx protein alone, while transient transfection of HBV replicon or HBx plasmid had no effect on the HNF4α level. Importantly, in the stable HBV- or HBx-expressing hepatocytes, the downregulated level of HNF4α was restored by inhibiting ERK signaling pathway. Our data showed that HNF4α was suppressed during long-term HBV infection in cultured HepG2-NTCP cells as well as in mouse model following hydrodynamic injection of pAAV-HBV or in mice intravenously infected with rAAV-HBV. Importantly, HNF4α downregulation increased cell proliferation which contributed to the formation and development of tumor in xenograft nude mice. The data presented here provided several proofs for the effect of HBV infection in manipulating HNF4α regulatory pathway in HCC development.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in the last decades improving life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the INK4 protein family specifically inhibit the CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in the other BC subtypes. In HER2-positive BC, combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, CDK4/6 inhibitors efficacy has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions of ongoing clinical trials and predictive biomarkers will be further debated.

A series of Si-bearing MgAl₂O₄-spinels were synthesized at 1500-1650 °C and 3–6 GPa. These spinels had SiO₂ contents up to ~1.03 wt%, and showed a substitution mechanism of Si⁴⁺ + Mg²⁺ = 2Al³⁺. Unpolarized Raman spectra were collected from polished single grains, and displayed a set of well-defined Raman peaks at ~610, 823, 856 and 968 cm^-1 which had not been observed before. Aided with the Raman features of natural Si-free MgAl₂O₄-spinel, synthetic Si-free MgAl₂O₄-spinel, natural low quartz, synthetic coesite, synthetic stishovite and synthetic forsterite, we infer that these Raman peaks should belong to the SiO₄ groups. The relations between the Raman intensities and SiO₂ contents of the Si-bearing MgAl₂O₄-spinels suggest that at some P-T conditions some Si must adopt the M-site. Unlike the SiO₄ groups with very intense Raman signals, the SiO₆ groups are largely Raman-inactive. We have further found that the Si cations primarily appear on the T-site at P-T conditions ≤ ~3–4 GPa and 1500 °C, but attain a random distribution between the T-site and M-site at P-T conditions ≥ ~5–6 GPa and 1630–1650 °C. This Si-disordering process observed for the Si-bearing MgAl₂O₄-spinels hints that similar Si-disordering might happen to the (Mg,Fe)₂SiO₄-spinels (ringwoodite), the major phase in the lower part of the mantle transition zone of the Earth and the index mineral for the very strong shock stage experienced by extraterrestrial materials. The likely consequences have been explored.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.

This study investigated the effects of a ten-visit individual coordinative locomotor training (CLT) program, including both a hands-on and a hands-off approach, on static and dynamic trunk stability in healthy adults with sedentary occupations. During the ten-visit program, the performance of eight subjects was monitored using a modified one-leg stance test in the sprinter and skater position, the Y-balance test, and the scapula and ischial tuberosity control test in the four-legged position. The data were analyzed using parametric and nonparametric statistics at an overall level of significance α=0.05. In the one-leg stance test, all subjects achieved a maximum value of 60 s on all ten visits. The improvement over time in the Y-balance test results was statistically significant for all directions (p<0.001). In addition, a statistically significant improvement in the Y-balance test composite score was observed between the first and the last visit (p=0.015-0.041). Subject-specific patterns were observed in the results of the Y-balance test. Significant improvements were observed over time in the four-legged position test score (p=0.008-0.010). Overall, the CLT program led to a significant improvement in trunk stability and leg extension in the anterior and posterolateral directions, as well as a reduction in instability as determined by the composite score of the Y-balance test.

Objective: The effect of long-term performance of one-bottle or two-bottle bonding agents on the shear bond strength to lithium disilicate ceramics (LDS) were to investigate, and the long-term performance of the bond strength of two-bottle bonding agent (Tokuyama Universal Bond II) was investigated under conditions without hydrofluoric acid solution (abbreviated as HF)-pretreatment of LDS. Methods: Nine resin cements (both self-adhesive and adhesive types) were used. It was investigated 1) the adhesion strength of various resin cements to LDS from the presence or absence of HF-treatment, 2) to determine the effect of the deterioration in three times [after one-day storage (abbreviated as Base), and after 5,000 &amp; 20,000 thermocycles (abbreviated as TC 5k and TC 20k)] of one- and two-component bonding agents. And the difference in degradation between one- and two-component bonding gents consist of the silane coupling agent was performed by chemical analysis (High Performance Liquid Chromatography). Results: The trends of resin cements were statistically not very different for each cement 3 times with HF-conditions. Also ESTECEM II and Super-Bond Universal showed the significant greatest values in two conditions (TC 5k and TC 20k) without HF-condition. In TC 20k, ESTECEM II &amp; Super-Bond Universal showed significantly better results than others when treated with the recommended bonding agents without HF-condition. In TC 20k, there was not much statistically significant difference if pretreated with Tokuyama Universal Bond II without HF-condition. Significance: When using LDS, it was found that long-term durability could be maintained by pretreating with Tokuyama Universal Bond II without pretreating with various hazardous HFs.

Radio-dynamic therapy (RDT), as an emerging cancer treatment method, has attracted attention due to its remarkable therapeutic efficacy using low-dose, high-energy radiation (such as X-rays), and has shown significant potential in cancer treatment. The RDT system typically consists of scintillators and photosensitizers. Scintillators absorb X-rays and convert them to visible light, activating nearby photosensitizers to generate cytotoxic reactive oxygen species (ROS). Challenges faced by the two-component strategy, including low loading capacity and inefficient energy transfer, hinder its final effectiveness. In addition, the tumor microenvironment (TME) with hypoxia and immunosuppression limits the efficacy of RDTs. Recent advances introduce one-component RDT systems based on nanomaterials with high-Z metal elements, which effectively inhibit deep-seated tumors. These novel RDT systems exhibit immune enhancement and immune memory, potentially eliminating both primary and metastatic tumors. This review comprehensively analyzes recent advances in the rational construction of RDTs, exploring their mechanisms and its application in the treatment of deep-seated tumors. Aimed at providing a practical resource for oncology researchers and practitioners, the review offers new perspectives for potential future directions in RDT research.

CRISPR/Cas9 technology is expected to offer novel genome editing-related therapies for various diseases. We previously showed that an adenovirus vector (AdV) possessing eight expression units of multiplex guide RNAs (gRNAs) was obtained with no deletion of these units. Here, we attempted to construct “all-in-one” AdVs possessing expression units of four and eight gRNAs with Cas9 nickase. We expected this to be difficult because extremely high copies of viral genomes during replication may cause severe off-target cleavages of host cells and induce homologous recombination. However, four units in the all-in-one AdV genome were maintained completely intact. For all-in-one AdV containing eight gRNA units, we shortened the U6 promoter of the gRNA expression units and enlarged the E3 deletion in the vector backbone to shorten the AdV genome within the adenovirus packaging limits. The final size of the all-in-one AdV genome containing eight gRNA units still slightly exceeded the reported upper limit. Nevertheless, approximately one-third of the eight units remained intact even upon preparation for in vivo experiments. Although the genome editing efficiency unexpectedly decreased upon enlarging the E3 deletion, our results suggested that all-in-one AdVs containing four and eight intact gRNA units could be obtained if the problems caused by the excessive size of the vector genome are solved.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified from the active surveillance (1/549, 0.18 %), during the Delta wave (1/175, 0.57 %). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. Our results demonstrate that, although uncommon, clinical infections in cats can and do occur.

The majority of Candida species are known as non-pathogenic yeasts and rarely involved in human diseases. However, recently case reports of human infections caused by non-albicans Candida species have increased, mostly in immunocompromised hosts. Our study aimed to describe and caracterise as thoroughly as possible, a new species of the Candida genus, named here Candida massiliensis (PMML0037), isolated from a clinical sample of human sputum. We compared genetic data based on the sequences of four genetic regions: "Internal Transcribed Spacers" of rRNA, D1/D2 domains (28S large subunit rRNA) and part of the genes encoding Translation Elongation Factor 1-α and β-tubulin2, to morphological characters, from scanning electron microscopy (TM 4000 Plus, SU5000), physiological, including the results of oxidation and assimilation tests of different carbon sources by the Biolog system, and chemical mapping by Energy-Dispersive X-ray Spectroscopy. Lastly, the in vitro antifungal susceptibility profile was performed using the E-testTM exponential gradient method. The multilocus analysis supported the genetic position of Candida massiliensis (PMML0037) as a new species of the genus Candida, and the phenotypic analysis highlighted its unique morphological and chemical profile when compared to other Candida species included in the study.

In mountain communities like Sebei, Uganda, that are highly vulnerable to emerging and reemerging infectious diseases, community-based surveillance plays an important role in the monitoring of public health hazards. In this survey, we explored capacities of Village Health Teams (VHTs) in Sebei communities of Mount Elgon in undertaking surveillance tasks for emerging and reemerging infectious diseases in the context of a changing climate. We used participatory epidemiology techniques to elucidate VHTs’ perceptions on climate change and public health and assess their capacities in conducting surveillance for emerging and reemerging infectious diseases. Overall, VHTs perceived climate change to be occurring with wider impacts on public health. However, they have inadequate capacities in collecting sur-veillance data. The VHTs lack transport to navigate through their communities and have in-sufficient capacities in using mobile phones for sending alerts. They do not engage in reporting other hazards related with the environment, wildlife and domestic livestock that would ac-celerate infectious disease outbreaks. Records are not maintained for disease surveillance ac-tivities and the abilities of VHTs to analyze data are also limited. However, VHTs have access to platforms that can enable them to disseminate public health information. The VHTs thus need to be retooled to conduct their work effectively and efficiently through equipping them with adequate logistics and knowledge on collecting, storing, analyzing, and relaying data, which will improve infectious disease response and mitigation efforts.

Motivated by diffraction experiments on the $\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$ reconstructed Si(111) due to deposition of rare earth elements (Dy, Tb) and silicide formation we analyse the splitting and non-splitting of superstructure spots. For this purpose, we model diffraction patterns for one dimensional structures generated by the binary surface technique and use supercell models to keep the analysis simple. Diffraction pattern are calculated in the framework of the kinematical diffraction theory and they are analyzed as a function of the domains and domain boundaries. Basic properties of the diffraction pattern are analyzed for model systems of a two-fold and a three-fold periodicity. The rules derived from these calculations are applied to the "real-world" system of Si(111)-($\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$)-RESi$2_{}$ (RE = Dy or Tb). Depending on the combination of domains and domain boundaries of different types a plethora of different features are observed in the diffraction patterns. These are analyzed to determine the sizes of both domain boundaries and domains from experimentally observed splitting of specific superstructure spots.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.

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.

Solution-based inorganic-organic halide perovskites are of great interest to researchers because of their unique optoelectronic properties and easy processing. However, polycrystalline perovskite films often show inhomogeneity due to residual strain induced during the film’s post-processing phase. In turn, these strains can impact both their stability and performances. An exhaustive study of residual strains can provide a better understanding and control of how they affect the performance and stability of perovskite films. In this work, we explore this complex interrelationship between residual strains and electrical properties for methylammonium \chemform{CH_3NH_3PbI_{3-x}Cl_x} films using grazing incident X-ray diffraction (GIXRD). We correlate with their resistiviy and carrier mobility using Hall effect. The sin^2($\psi$) technique is used to optimize the annealing parameters for the perovskite films. We also establish that temperature-induced relaxation can yield significant enhancement of the charge carrier transports in perovskite films. Finally, we also use Raman micro-spectroscopy to assess the degradation of perovskite films as a function of their residual strains.

Today, various dietary supplements are taken to improve endurance performance during physical activity. These supplements have proven to be very successful in controlling and balancing various hormone levels and have contributed to the prevention and healing of metabolic disorders and physical injuries. In this study, we sought to investigate the effects of the ACTN3 gene and nutrient supplementation, including beta-alanine, ashwagandha, L-carnitine, and iron, on athletic performance. The ACTN3 gene has been identified as a potential genetic determinant of athletic performance, particularly in activities that require high levels of power and strength. This study investigated the interaction between the ACTN3 gene and supplementation and highlighted the potential for personalized approaches to improve athletic performance. 24 subjects per group, were randomized in a parallel-group design to examine the effects of supplementation on the ACTN3 gene and athletic performance over a 21-day intervention period. Participants in the intervention were divided into four groups of six members each. The same subjects who did not take supplements formed the control group. In addition, the subjects were divided into 4 groups (G1, G2, G3, and G4), each consisting of subgroups of control and a treated. All treated groups (TG1, TG2, TG3, and TG4) received 4 supplements for 21 days, namely S1 (ashwagandha), S2 (iron), S3 (beta-alanine) and S4 (L-carnitine), together with the 4 control groups, i.e. CG1, CG2, CG3 and CG4, who received no supplements during the same period. In particular, this study determines the effect of these 4 supplements on actn3 gene expression, testosterone, cholesterol and BUN levels of the participants. The P-values determined for all parameters showed statistically significant values and the final result showed that all supplements had positive effects on the tested parameters. The result showed a highly significant difference between the intake of supplements before and after the intake of 24 athletes per group on the ACTN3 gene expression level and biochemical indicators.

LPA3 receptors were expressed in TREx HEK 293 cells, and their signaling and phosphorylation were studied. The agonist, lysophosphatidic acid (LPA), increased intracellular calcium and ERK phosphorylation through pertussis toxin-insensitive processes. Phorbol myristate acetate, but not LPA, desensitizes LPA3-mediated calcium signaling. The agonists and the phorbol ester-induced LPA3 internalization. Pitstop 2 (clathrin heavy chain inhibitor) markedly reduced LPA-induced receptor internalization; in contrast, phorbol ester-induced internalization was only delayed. LPA induced rapid β-arrestin-LPA3 receptor association. The agonist and the phorbol ester induced marked LPA3 receptor phosphorylation, and phosphorylation sites were detected using mass spectrometry. Phosphorylated residues were detected in the intracellular loop 3 (S221, T224, S225, and S229) and in the carboxyl terminus (S321, S325, S331, T333, S335, Y337, and S343). Interestingly, phosphorylation sites are within sequences predicted to constitute β-arrestin binding sites. These data provide insight into LPA3 receptor signaling and regulation.

It is essential to have a thorough knowledge of the genetic variation among different strains of Xanthomonas citri pv. citri (Xcc), which is responsible for causing citrus bacterial canker. This understanding is important for studying the disease’s characteristics, population structure, and evolution, and ultimately for developing sustainable methods of control. A total of 48 strains, obtained from citrus production areas in Burkina Faso in 2012, 2020, and 2021, were subjected to polymerase chain reaction (PCR) tests using specific primers. The aim was to examine the distribution of type 3 effectors (T3E) and determine the geographical origins of the strains. The examination of the distribution of type 3 non-transcription activate like effectors (TALE) indicates a broader range in strains obtained in 2020 and 2021 compared to those obtained in 2012. However, all strains possess a shared set of three genes, specifically XopE2, XopN, and AvrBs2. Furthermore, all examined effectors were observed in the Bobo-Dioulasso region. Regarding the characterization of TALEs, two profiles containing two to three TALEs were discovered. Profile 1, consisting of two TALEs, was found in 37 Xcc strains, whereas Profile 2, comprising three TALEs, was detected in 11 strains. Out of the three TALEs (A, B, and C) that were identified, TALEs B and C were present in all strains. The correlation matrix indicated a positive association between the T3E content of strains and the duration of their isolation. Principal component analysis revealed a limited organization of the strains under investigation

A comprehensive understanding of the genetic diversity among strains of Xanthomonas citri pv. citri (Xcc), the causative agent of citrus bacterial canker, is crucial for unraveling the pathological nature, structure, and evolution of populations, thereby facilitating the adoption of sustainable control measures. In a collection of 48 strains isolated in 2012, 2020, and 2021 from citrus production areas in Burkina Faso, polymerase chain reaction (PCR) tests utilizing specific primers were conducted to investigate the distribution of type 3 effectors (T3E) and the structuring of strains based on their geographical origins. The analysis of the distribution of type 3 non-transcription activate like effectors (TALE) reveals a more extensive repertoire in strains isolated in 2020 and 2021 compared to those isolated in 2012. Nevertheless, all strains share a common repertoire of three genes, namely XopE2, XopN, and AvrBs2. Additionally, all screened effectors were observed in the Bobo-Dioulasso locality. Concerning the characterization of TALEs, two profiles consisting of two to three TALEs were identified. Profile 1, with two TALEs, was present in 37 Xcc strains, while Profile 2, with three TALEs, was identified in 11 strains. Among the three TALEs (A, B, and C) identified, TALEs B and C were common to all strains. The correlation matrix revealed a positive correlation between the T3E content of strains and the years of their isolation. Multiple component analysis indicated a weak structuring of the tested strains.

Inflammation is a conserved process that involve the activation of immune and non-immune cells aiming at protecting the host from bacteria, viruses, toxins and injury. However, unresolved inflammation and permanent release of pro-inflammatory mediators are responsible for the promotion of a condition called “low-grade systemic chronic inflammation”, characterized by tissue and organ damages, metabolic changes and increased susceptibility to non-communicable diseases. Several studies have demonstrated that different dietary components may influence modifiable risk factors for diverse chronic human pathologies. Marine n-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), are well recognized anti-inflammatory and immunomodulatory agents able to influence many aspects of the inflammatory process. The aim of this article is to review the recent literature that relates to the modulation of human disease, such as rheumatoid arthritis, by n-3 PUFAs.

This study presents the design and implementation of a PLC microprocessor adhering to the IEC-61131-3 standard, executed on a Cyclone-V FPGA using a DE10-NANO development board. Our microprocessor optimizes the central processing unit by streamlining the data path, achieving a remarkable simulated response time of approximately 60 ns, equivalent to three clock cycles at a 50MHz frequency for Boolean operations. To substantiate our approach, we conducted practical experiments utilizing a FESTO conveyor station, employing relays as actuators, and incorporating optical and inductive sensors. The results underscore the feasibility of our proposed approach and serve as practical validation of its efficacy. This work introduces a promising avenue for the development of cost-effective PLCs employing SoC FPGA variants. Additionally, a thorough comparison of execution times with other early reported architectures. Our microprocessor outperforms even well-established PLCs like the S7-312, with substantial reductions in execution times of 94.54% for floating-point operations, 71.42% to 93.33% for word operations, and up to 78.57% for bit operations.

Rapid analysis and characterization of compounds by mass spectrometry may overlook trace compounds, although targeted analysis methods can significantly improve detection sensitivity, it is difficult to discover novel scaffold compounds. This study developed a strategy for discovering trace compounds in the aging process of traditional Chinese medicine based on MS fragmentation and known metabolic pathway. Specifically, we found that the characteristic component of C. reticulata 'Chachi', methyl N-methylanthranilate (MMA), fragmented in ESI-CID to produce rearrangement ion 3-hydroxyindole, which has been proven to exist in trace amounts in C. reticulata 'Chachi' comparing with the reference substance by LC-MS/MS. By combining the known metabolic pathways of 3-hydroxyindole and the possible methylation reactions that may occur during aging, 10 possible indole derivatives were untargeted predicted. These compounds were confirmed to originate from MMA by purchasing or synthesizing reference substances and all of them were detected in C. reticulata 'Chachi' through LC-MS/MS analysis, achieving trace compound analysis from untargeted to targeted. It may contribute to explain the aging mechanism of C. reticulata 'Chachi' and the strategy of CID-induced special rearrangement ion binding metabolic pathway has potential application value in discovering trace compounds.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene RRAS2 has emerged as both a driver oncogene and a potential marker for CLL progression, with higher RRAS2 expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of RRAS2 have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and RRAS2 mRNA expression, which correlated with lower blood lymphocytosis and better prognosis. These findings highlight the importance of RRAS2 overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.

Background: Galectin-3 (Gal-3) overexpression is associated with fibroblastic proliferation and the production of collagen, resulting in increased cardiac fibrosis and remodelling. Aim of the study was to investigate on the expression of Gal-3 in hypertrophic hearts. We examined 19 surgical specimens taken from interventricular septum of 8 patients with Tetralogy of Fallot, 4 patients with aortic valve stenosis, 1 cardiac explant affected from dilated cardiomyopathy, and 6 myocardial biopsies of patients submitted to heart transplantation. Methods: All the samples were routinely processed, stained with Hematoxylin-Eosin, Trichromic stain and elastic fiber stain and selected by having the morphological features of myocardial hy-pertrophy: myocytolysis, nuclear pleomorphism, interstitial fibrosis. Results: At immunohistochemistry, myocardial fibers showed cytoplasmic expression of Gal-3 in the 4 patients with aortic valve stenosis (diffuse in 3 and mild in 1), in the 1 patient with cardiac explant (mild) and in the 4/6 transplanted hearts (mild and focal in 3 and diffuse in 1). The 8 patients affected from Tetralogy of Fallot and 2 patients with transplanted hearts resulted negative. Conclusions: The results agreed with the hypothesis that Gal-3 may play a role in cardiac hyper-trophy; its expression in myocardial fibers is not related with the morphological aspects as suggested by the absence in pediatric cases. The presence in myocardial biopsies taken from transplanted hearts would suggest a possible role in predicting clinical outcome of such patients.

Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system. In individuals with ASD, there is an increase in bacterial genera such as Clostridium, as well as species involved in the synthesis of branched-chain amino acids (BCAA) like Prevotella copri. Conversely, decreased amounts of Akkermansia muciniphila, and Bifidobacterium spp. are observed. Epigallocatechin gallate (EGCG) is one of the polyphenols with the greatest beneficial activity on microbial growth and its consumption is associated with reduced psychological distress. Therefore, the objective of this review is to analyze how EGCG and its metabolites can improve the microbial dysbiosis present in ASD and its impact on the pathology. The analysis reveals that EGCG inhibits the growth of pathogenic bacteria like Clostridium perfringens and Clostridium difficile. Moreover, it increases the abundance of Bifidobacterium spp. and Akkermansia spp. As a result, EGCG demonstrates efficacy in increasing the production of metabolites involved in maintaining epithelial integrity and improving brain function. This identifies EGCG as highly promising for complementary treatment in ASD.

Galectins have been shown to have roles in cancer progression via contributions to angiogenesis, metastasis, cell division, and evasion of immune destruction. This study analyses galectin-1, -3, and -9 serum concentrations in breast cancer patients by enzyme-linked immunosorbent assay (ELISA) against the characteristics of the patient and tumor such as stage, molecular subtype, and receptor expression. Galectin-9 was found to be statistically significantly increased in HER2 enriched tumors as well as being reduced in patients with hormone receptor positive tumors and increased in patients with HER2 amplified tissues. Galectin-1 was found to be statistically significantly increased in the serum of patients who had undergone hormonal, immunotherapy, or chemotherapy. These findings provide insight as to the changes in galectin levels during cancer progress, response to treatment and molecular phenotype. These findings are valuable in the further understanding of the relationships of galectin and tumor biology and can inform future research on therapeutic targets for galectin inhibitors and the utility of galectin biomarkers.

Seafood products are the main dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, due to the widespread use of processed fish products, the presence of these n-3 PUFAs may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, with a focus on n-3 polyunsaturated fatty acids (n-3 PUFAs), in different processed fish and shellfish food of EU and non-EU origin purchased in supermarkets and ethnic food shops in Messina (Italy), using gas chromatography with flame-ionization detector (GC-FID). From the fatty acid profile, the atherogenic index (AI), thrombogenicity index (TI) and flesh-lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.31-9.84 (TI) and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids had the following ranges: 13.55-50.48%, 18.91-65.58%, 13.84-52.73%, respectively. All samples showed a good presence of PUFAs and, in particular, eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) were the main n-3 polyunsaturated fatty acids (n-3 PUFA).

In an historic perspective on the development of the Standard Model of particle physics it is shown how mathematically driven axioms have masked the merits of a physically comprehensible structural view. It is concluded that the difference between the two approaches can be traced back to two major issues. Whereas in the Standard Model the quark is a Dirac particle with a single real dipole moment, the quark in the structural model, in confinement with other quarks, is a Dirac particle with two real dipole moments. The second issue is the view that empty space does not exist, but that space is filled with a polarisable energetic fluid. It is shown how recognition of these two issues pave a road to reconcile particle physics with gravity, in which the quark can be seen as a magnetic electron and in which the gluon, as the strong force carrier, can be seen as a massive photon.

According to the risk investigations of being involved in an accident, alcohol-impaired driving is one of the major causes of motor-vehicles accidents. Preventing highly intoxicated persons from driving would potentially save many lives. This paper proposes a lightweight in-vehicle alcohol detection that processes the data generated from 6-alcohol sensors (MQ-3 Alcohol Sensors) using an optimizable shallow neural network (O-SNN). The experimental evaluation results exhibit a high-performance detection system scoring a 99.8% of detection accuracy with a very short inferencing delay of 2.22 µ seconds. Hence, the proposed model can be efficiently deployed and used to discover in-vehicle alcohol with high accuracy and low inference overhead as a part of the driver alcohol detection system for safety (DADSS) system aiming at massive deployment of alcohol sensing systems that could potentially save thousands of lives annually.

Fusarium culmorum is a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotoxins of the trichothecene B group. These toxins are also produced by F. graminearum species complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates of F. graminearum from North America. Only these isolates and a few strains of a yet to be characterized Fusarium species from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20 F. culmorum strains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). In F. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded by TRI1 that is unable to oxidize C-8. In F. culmorum, producers and nonproducers of NX-2 possess identical TRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature of F. culmorum.

The physicalchemistry properties and crystal structure of were nano-ZrO₂+3mol.%Y₂O₃ determined. The kinetics of the formation of H₂ as a result of the decomposition of H₂O on the surface of nano-ZrO₂+3mol.%Y₂O₃ was studied. Effects of adsorption and desorption process on ZrO₂+3 mol.%Y₂O₃ nanoparticles were studied at different (T=400÷1000⁰C) temperature. The study of H₂ in thermal processes at nano-ZrO₂+3 mol.%Y₂O₃ system increased. Such an increase in H₂ generation in comparison with a pure H₂O as thermal processes had formedactive centers for H₂O decomposition on the surface of the catalyst at the expense of δ-electrons emitted on the surface of nano-ZrO₂+3 mol.%Y₂O₃. This showed that the dimensions of the studied nanoscale particles systems are comparable to the free running distance of energy carriers generated by of nano-ZrO₂+3 mol.%Y₂O₃ as a result of thermal processes. These results are promising for hydrogen generation by waer spliting in near future.

(1) Background: Mouse-mammary tumor virus (MMTV) might play a role in the etiology of some breast cancers in humans. The purpose of our study was to identify MMTV DNA sequences in breast tissue samples from breast cancer patients operated in our regional center from Romania. (2) Methods: We have selected 75 patients with non-metastatic breast cancer treated with curative intent and searched with PCR the MMTV-like DNA sequence in the breast cancer tissue and normal breast tissue obtained from the same patients. (3) Results: None of the examined samples was positive for MMTV-like target sequences on PCR. (4) Conclusions: We could not prove that MMTV plays a role in the etiology of breast cancer in our patient group. This finding is similar to findings of other geographically related research groups and might be due to the fact that only the Mus musculus domesticus mouse species was proven to carry infectious MMTV, but not the Mus musculus musculus species, which is specific to South-Eastern Europe and some parts of Asia.

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

We reported previously that poly (3-hydroxybutyrate) (PHB) oligomer is an effective antimicrobial agent against gram-positive bacteria, gram-negative bacteria, fungi and multi-drug resistant bacteria. In this work, it was further found that polyethylene glycol (PEG) can promote the antimicrobial effect of PHB oligomer synergistically. Three hypothetic mechanisms were proposed, that is, generation of new antimicrobial components, degradation of PHB macromolecules and dissolution/dispersion of PHB oligomer by PEG. With a series of systematic experiments and characterizations of HPLC-MS, it was deducted that dissolution/dispersion of PHB oligomer dominated the synergistic antimicrobial effect between PHB oligomer and PEG. This work demonstrates a way for promoting antimicrobial effect of PHB oligomer and other antimicrobial agents through improving hydrophilicity.

The regioselectivity in non-polar [3+2] cycloaddition (32CA) reactions has been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) level. To this end, the 32CA reactions of nine simplest three-atom-components (TACs) with 2-methylpropane were selected. The electronic structure of the reagents has been characterised through the Electron Localisation Function (ELF) and the Conceptual DFT. The energy profiles of the two regioisomeric reaction paths and ELF of the transition state structures are studied to understand the origin of the regioselectivity in these 32CA reactions. This MEDT study permits to conclude that the least electronegative ends X1 atom of these TACs controls the asynchronicity in the C-X (X = C,N,O) single bond formation, and consequently, the regioselectivity. This behaviour is a consequence of the fact that the creation of the non-bonding electron density required for the formation of the new CX single bonds has a lesser energetic cost at the least electronegative X1 atom than that at the Z3 one.

This paper reports on the fabrication of alumina doped preforms using MCVD-vapor phase chelate delivery system with Al(acac)3 as the precursor. The objectives of the work are to study the deposition process, the efficiency of the fabrication process, and the quality of the fabricated fiber preforms. Two parameters are studied, Al(acac)3 sublimator temperature (TAl°C) and deposition direction (i.e. downstream and upstream). Other parameters such as oxygen flow and deposition temperature are fixed. The results showed that a high uniformity of refractive index difference (%RSD &lt; 2%) and core size (%RSD &lt; 2.4%) was obtained along the preform length using downstream deposition while for the combined upstream and downstream deposition the uniformity was deteriorated. The process efficiency was found to be about 21% for TAl°C of 185°C and downstream deposition. From the EDX elemental analysis, the refractive index was found to increase by 0.0025 per mole percent of alumina.

Cadmium (Cd) is a heavy metal that suppresses plant growth; however, application of endophytic bacteria can increase resistance of plants against Cd, as well as improve plant growth. Two bacterial endophytic strains were isolated from Solanum nigrum and were identified as Serratia sp. AI001 and Enterobacter sp. AI002 by 16S DNA sequencing. Strains AI001 and AI002, tolerated up to 25 mg/mL Cd in broth culture and showed phosphate solubilization potential in Pikovskaya agar medium. AI001 and AI002 produced indole-3-acetic acid, which was confirmed by gas spectrometry-mass chromatography. Brassica plants stressed with 0, 5, 15, and 25 mg/L Cd showed significant decrease in plant growth, chlorophyll content and biomass, and significant increase in Cd dose-dependent electrolyte leakage. Inoculation of strain AI001 or AI002 significantly enhanced the plant growth attributes of shoot length, root length, chlorophyll content, and biomass as compared to those in uninoculated plants. Reduced glutathione contents in plants stressed with different concentrations of Cd also increased with inoculation of AI001 and AI002. The reason of Cd resistance enhancement in plants by inocula could be due to their greater plant growth promoting activities as well as their antioxidative response.

Fish oil rich in polyunsaturated omega-3 fatty acids is extracted in high yield from anchovy filleting waste using d-limonene as green biosolvent in a simple solid-liquid extraction performed by mechanically stirring and maceration followed by limonene removal via evaporation under reduced pressure. As limonene is renewably obtained from waste orange peel, this protocol establishes a circular bioeconomy method to obtain valued omega-3 extracts from biowaste available worldwide in several million t/year amount. The method closes the materials cycle and opens the route to full valorisation of an important biological resource so far mostly discarded as waste. Significant economic opportunities benefiting local communities, the ecosystem and public health are anticipated.

The adsorption of carbon dioxide on amino silanes-functionalized MCM-41 and SBA-15 materials is reported. The functionalization of mesoporous silicas was made by post-synthesis method, by impregnation of 3-aminopropyltriethoxysilane. The obtained materials were characterized by X-ray diffraction, scanning and transmission electron microscopies, nitrogen adsorption-desorption and X-ray photoelectron spectroscopy measurements. The carbon dioxide adsorption capacities for the samples were carried out under ambient pressures. The obtained results evidenced that amino-silanes with a terminal amine (–NH₂) were functionalized through covalent coupling of this group on the surface of the channels in the ordered mesoporous silica, meaning that the amine is anchored on the surface of the bigger pores of the MCM-41 and SBA-15 support. For functionalized materials, the CO₂ adsorption capacity of the AMCM-41 increased from 0.18 to 1.1 mmol·g⁻¹, whereas for ASBA-15, it was from 0.6 to 1.8 mmol·g⁻¹. The Lagergren kinetic algorithms were applied in order to validate the obtained results, evidencing the enhanced carbon dioxide adsorption capacity and stability of the functionalized ordered mesoporous molecular sieves.

Oenothera flower petals change color during senescence. When in full bloom, the flowers of O. tetraptera are white and those of O. laciniata and O. stricta are yellow; however, the colors change to pink and orange, respectively, when the petals fade. We analyzed the flavonoid components in these petals as a function of senescence using HPLC-DAD and LC-MS. In all three species, cyanidin 3-glucoside (Cy3G) was found in faded petals, and the content of Cy3G increased in senescence. In full bloom (0 h), no Cy3G was detected in any of the petals, but after 12 h, the content of Cy3G in O. tetraptera was 0.97 μmol/gFW and that in O. laciniata was 1.82 μmol/gFW. Together with anthocyanins, major flavonoid components in petals were identified. Quercitrin was detected in the petals of O. tetraptera, and isosalipurposide was found in the petals of O. laciniata and O. stricta. The content of quercitrin did not change during senescence, but that of isosalipurposide in O. laciniata increased from 3.4 μmol/gFW at 0 h to 4.8 μmol/gFW at 12 h. The color change in all the three Oenothera flowers was confirmed to be due to the de novo biosynthesis of Cy3G.

In this paper, we analyze the measurements of the normalized radar cross-section(NRCS) in Wave Mode for Chinese C-band Gaofen-3(GF-3) synthetic aperture radar (SAR). Based on 2779 images from GF-3 quad-polarization SAR in Wave Mode and collocated wind vectors from ERA-Interim, we verify the feasibility of using ocean surface wind fields and VV-polarized NRCS to perform normalized calibration. The method uses well-validated empirical C-band geophysical model function (CMOD4) to estimate the calibration constant for each beam. The Amazon rainforest experiment results show that the accuracy of obtained calibration constant meets the requirements. In addition, the relationship between cross-pol NRCS and wind vectors is discussed. The cross-pol NRCS increases linearly with wind speed and it has an approximate cosine modulation with the wind direction when the wind speed is greater than 8m/s. The cross-polarized system noise floor is low enough to ignore it in wind retrieval. Furthermore, we also investigate the properties of the polarization ratio, denoted PR, and show that it is dependent on incidence angle and azimuth angle. Two empirical models of the PR are fitted, one as a function of incidence angle only, the other with additional dependence on azimuth angle. Assessments show that the σ_VV^0 retrieved from new PR models as well as σ_HH^0 is in good agreement with σ_VV^0 extracted from SAR images directly. And it is also shown that considering the azimuth angle can improve polarization conversion accuracy.

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16–24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, H3K14ace, and H3K27ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.

Obesity is a major risk factor for the development of life-threatening malignant ventricular tachyarrhythmias (VT) and sudden cardiac death (SCD). Risks may be highest for patients with high levels of the proinflammatory cytokine interleukin (IL)-6. We used our guinea pig model of high-fat diet (HFD) induced Ventricular arrhythmias, that exhibit heightened proinflammatory-like pathology which is also observed in human obesity VT, as well as immunofluorescence, and confocal microscopy approaches to evaluate the pathological IL-6 trans-signaling function and explore the underlying mechanisms. Using blind-stick and electrocardiogram (ECG) techniques, we tested the hypothesis that heightened IL-6 trans-signaling exhibit enhanced Ventricular arrhythmias /SCD incidence and underlying arrhythmia substrates. Remarkably, compared to low-fat (LFD) diet fed controls, HFD promotes phosphorylation of the IL-6 signal transducer and activator of transcription 4 (STAT4) leading to its activation and enhanced nuclear translocation of pSTAT4/STAT4 more than LFD controls and pSTAT3/STAT3 nuclear expression. Overactivation of IL-6 trans-signaling in guinea pigs prolonged the QT interval that resulted in greater susceptibility to VT/SCD with isoproterenol challenge, as also observed with the downstream Janus kinase (JAK) 2 activator. These findings may have potentially profound implications for more effective VT therapy in the vulnerable obese patient population.

Introduction: A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). Material and Methods: The study analysed articles published in JCR journals from 2019 to 2024, including retrospective, prospective, case-control, or cross-sectional studies. It combined MESH and free terms for "Epileptogenesis" and "Neuroinflammation" and included searches for biomarkers previously reported in narrative reviews. Results: The study analysed 243 articles related to epileptogenesis and neuroinflammation, with 356 from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 52 evaluated by authors. 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. This systematic review provides acceptable support for five biomarkers: TNF-a and some of its soluble receptors (sTNFr2), HMGB1 and TLR-4, CCL2 and IL-33. Discussions: Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control levels of epileptic patients. Their value will be better defined by future studies.

Owing to their extensive biological potential, essential oils (EOs) and their bioactive phytochemicals have gained attention from the scientific community. Within this domain, Terpinen-4-ol (T-4-ol), a bioactive monoterpene alcohol and the major constituent of tea tree oil (TTO), has made its way into translational research. Recent literature on T-4-ol strongly indicates its diverse pharmacological properties, including but not limited to antimicrobial, antivirulent, antioxidant, anti-inflammatory, anti-hypertensive, and anti-cancer effects. Hence, this review provides a comprehensive overview of the multifaceted biological activities exhibited by T-4-ol, emphasizing its medicinal potential for widescale application. The antibacterial and antifungal effectiveness of T-4-ol has been discussed encompassing its role in combating a broad spectrum of bacterial and fungal pathogens, respectively. The review delves into the antivirulent prospects of T-4-ol, shedding light on its ability to attenuate virulence and mitigate bacterial pathogenesis. Scientific literature on the antioxidant and anti-inflammatory activity of T-4-ol highlighting its role in neutralizing reactive oxygen species and modulating inflammatory pathways has also been collated. Furthermore, the review elaborates on the cardioprotective and anti-hypertensive properties of T-4-ol and augments literature on its anti-cancer mechanism against various cancer cell lines. Overall, this review consolidates the existing knowledge on T-4-ol, providing a holistic understanding of its pharmacological abilities. The exploration of these diverse attributes positions T-4-ol as a promising candidate for further research and therapeutic repurposing in various biomedical applications.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

This research aims to find out whether the synthetic 1, 2, 4-triazine and its derivatives have antifungal effects and can protect humans from infection with Candida albicans. Molecular docking and molecular dynamic simulation are widely used in modern drug design to target a We are interested in using molecular docking and molecular dynamics modelling to investigate the interaction between the derivatives of 1, 2, 4-triazine and the resulting lanosterol 14 - demethylase (CYP51) of Candida albicans The inhibition of Candida albicans CYP51 is the main goal of our research. The 1, 2, 4-triazine and its derivatives have been docked to the CYP51 enzyme, which is involved in Candida albicans Multidrug Drug Resistance (MDR). Autodock tools were used to identifying the binding affinities of molecules against the target proteins. Compared to conventional fluconazole, the molecular docking results indicated that each drug has a high binding affinity for CYP51 proteins and forms unbound interactions and hydrogen bonds with their active residues and surrounding allosteric residues. The docking contacts were made using a 10 ns MD simulation with nine molecules. RMSD, RMSF, hydrogen bonds, and the Rg all confirm these conclusions. In addition, these compounds were expected to have a favorable pharmacological profile and low toxicity. The compounds are being offered as scaffolds for the development of new antifungal drugs and as candidates for future in vitro testing.

Infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of the Spike S1 protein encoding mRNA, incorporated in a lipid nanoparticle, stabilized by polyethylene glycol (PEG). mRNA vaccines are novel in many respects, including cellular uptake, the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences encoding the SARS-CoV-2 Spike S1 protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to induction of virus neutralizing antibodies and cytotoxic T-lymphocytes will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. mRNA based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG, and potential presentation in the context of CD1 will be discussed. Adenovirus vector based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

In 2019, Chinese government implemented the first round of National Centralized Drug Procurement (NCDP) pilot (so-called "4+7" policy) in mainland China, achieved a prominent price reduction of 52% on average for 25 bidding winning products. Under cross-price elasticity theory, the price behavior of pharmaceutical enterprises for policy-related drugs might change. This study used drug purchasing data from the Centralized Drug Procurement Survey in Shenzhen 2019, and applied single-group Interruption Time Series (ITS) design to examine the impact of "4+7" policy on the drug price index (DPI) of policy-related drugs. The ITS analysis showed that the DPI of winning (-0.183 per month, p&lt;0.0001) and non-winning (-0.034 per month, p=0.046) products significantly decreased after the implementation of "4+7" policy. No significant difference was found for the immediate change of DPI for alternative drugs (p=0.537), while a significant decrease in change trend was detected in the post-"4+7" policy period (-0.003 per month, p=0.014). The DPI of the overall policy-related drugs significantly decreased (-0.261 per month, p&lt;0.0001) after "4+7" policy. These findings indicate that the price behavior of pharmaceutical enterprises changed under NCDP policy, while the price linkage effect is still limited. It is necessary to further expand the scope of centralized purchased drugs and strengthen the monitoring of related drugs regarding price change and consumption structure.

Soil organic carbon (SOC) sequestration in arable soils is a challenging goal for soil management. Multiple factors should be considered for the prediction of the soil capacity to fix atmospheric carbon. In this study, we focused on the effect of crop rotation and previous land use for future carbon sequestration on two experimental fields with identical soils (Retisols) and input of organic fertilizers. We analyzed the SOC dynamics and used the Roth C model to forecast SOC changes under RCP4.5 and RCP8.5 scenarios. Our experimental and modelling results indicated a consistent increase in SOC stocks and the stable fractions of soil organic matter (SOM). The increase in SOC was higher in the experiment with the crop-grassland rotation that in the experiment with a rotation of row crops and barley. With similar total SOC stocks, the efficiency of soil management differed as reflected by the contrasting composition of SOM, as fields with a long cultivation history showed higher SOM stability. The goal of 4‰ annual increase of SOC stocks may be reached under crop- grassland rotation in 2020-40 and 2080-90 when applying mineral or organic fertilizer system for scenario RCP4.5, and mineral fertilizer system in 2080-2090 for scenario RCP8.5.

Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis. This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.

The grain size of CVD (Chemical Vapor Deposition) graphene was controlled by changing the precursor gas flow rates, operation temperature, and chamber pressure. Graphene of average grain sizes of 4.1 µm, 2.2 µm, and 0.5 µm were synthesized in high quality and full coverage. The possibility to tailor the thermoelectric conversion characteristics of graphene has been exhibited by examining the grain size effect on the three elementary thermal and electrical properties of σ, S, and k. Electrical conductivity (σ) and Seebeck coefficients (S) were measured in a vacuum for supported graphene on SiO₂/Si FET (Field Effect Transistor) substrates so that the charge carrier density could be changed by applying a gate voltage (V_G). Mobility (µ) values of 529~1042, 459~745, and 314~490 cm²/V·s for the three grain sizes of 4.1 µm, 2.2 µm, and 0.5 µm, respectively, were obtained from the slopes of the measured σ vs. V_G graphs. The power factor (PF), the electrical portion of the thermoelectric figure of merit (ZT), decreased by about one half as the grain size was decreased, while the thermal conductivity (k) decreased by one quarter for the same grain decrease. Finally, the resulting ZT increased more than two times when the grain size was reduced from 4.1 µm to 0.5 µm.

The current report contributes to the understanding of the stereoselectivity of the chiral dirhodium(II) carboxylate catalysts derived from N-protected amino acid ligands. Investigating the possible effect of ligand stereo-purity on catalyst structure and enantioselectivity was carried out. This was justified through a new X-ray crystal structure for Rh2(S,S,S,R-PTTL)4 diastereomer.

The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. Recently, we generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models. Our published data have shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing local and systemic oxidative stress and synergistically suppressing steatosis, inflammatory reactions, and/or apoptotic activity. These observations suggest that Tg mice may be a useful animal model for studying the relevance of oxidative stress on inflammation and the dysregulation of lipid/bile acid/glucose metabolism upon the progression of human metabolic syndrome, and that specific accelerators of PRDX4 may be useful as therapeutic agents for ameliorating various chronic inflammatory diseases.

The burden of bacterial bloodstream infections (BSIs) is rapidly increasing in Africa including Rwanda. This is a retrospective study investigates the diversity, distribution, and antimicrobial susceptibility profiles of BSIs bacteria in three tertiary referral hospitals in Rwanda between 2020 and 2022. A total of 1,532 blood culture tests were performed for visiting patients. Overall, the proportions of Gram-negative and Gram-positive bacteria were 48.2% and 51.8, respectively. Staphylococcus aureus was the predominant species accounting for 25% of all Gram-positive BSIs species and Klebsiella species representing 41% of all Gram-negative BSIs species. Antimicrobial susceptibility testing revealed that Amikacin exhibited the highest activity against Enterobacter spp., Serratia spp. and Escherichia coli in &gt;92% of cases and Klebsiella spp. in 75.7%. Meropenem and Imipenem were highly efficacious to Salmonella spp. (100% susceptibility), Enterobacter spp. (96.2% and 91.7%, respectively), and Escherichia coli (94.7% and 95.5%, respectively). The susceptibility of Enterococcus spp., S. aureus, and Streptococcus spp. to Vancomycin was 100%, 99.5% and 97.1%, respectively. Klebsiella spp. was highly sensitive to Colistin (98.7%), Polymyxin B (85.6%), Imipenem (84.9%), and Meropenem (78.5%). We recommend strengthening the implementation of integrated transdisciplinary and multisectoral One Health including AMR-stewardship for the surveillance, prevention, and control of AMR in Rwanda.

The aim of this work was to investigate a new, simple one-pot combustion synthesis technique for creating sulphur-based CuS/ZnS p-n heterojunction nanocomposite photocatalysts. The study examined the photocatalytic activity and reusability of these nanocomposites in removing rhodamine B (RhB) dye under visible light irradiation. Various methods of characterisation were employed to determine the properties of the materials, including particle morphology, crystalline phases and bandgap energy. The intrinsic reaction parameters, such as catalyst loading, pH level of the solution, and initial pollutant concentration, were varied to establish the optimal photo-degradation conditions. The results showed that a binary CuS/ZnS catalyst with a 10 gL-1 loading, at pH 5, degraded 97% of 5 ppm RhB dye after 270 minutes of visible light irradiation. Addition-ally, this composite catalyst exhibited excellent chemical stability and reusability, achieving 83% RhB dye removal after five recycling runs. Scavenger tests identified the photogenerated holes (h+) and superoxide free radicals (•O2) as the primary reactive species responsible for degradation. This study provides valuable insight into the design of highly efficient nanomaterials for removing organopollutants in wastewater, and a possible reaction mechanism is proposed.

Transcriptional regulations have been widely studied as one of the main bridges between biology and other basic sciences as well as medicine. The traffic across it has been mostly unidirectional: chemistry and physics provided a lot of tools for biology, although the supply is now saturating. The traffic in opposite direction, the supply of subjects to develop chemistry and physics, has been only a little. However, if there are any, the supply will be at least from transcription, because the notion of chemical reaction is the strongest. This topic is aimed to increase the opposite traffic by introducing the forefront of physicochemical studies of transcription.

The article presents the original derivation method of transformations for kinematics with a universal reference system. This method allows to derive transformations that meet the results of the Michelson-Morley and Kennedy-Thorndike experiments only in some frame of reference, e.g. in laboratories moving in relation to a universal frame of reference with small speeds. The obtained transformations are the basis for the derivation of the new physical theory, which has been called the Special Theory of Ether. The generalized transformations can be expressed by relative speeds (26)-(27) or by the parameter δ (v) (37)-(38). Based on conclusions of the Michelson-Morley’s and Kennedy-Thorndike’s experiments, the parameter δ (v) was determined. This allows the transformations to take a special form (81)-(82), which is consistent with experiments in which velocity of light is measured. On the basis of obtained transformations, the formulas for summing speed and relative speed were also determined. The entire article includes only original research conducted by its author.

The Microwave Humidity and Temperature sounder (MWHTS) on board the Fengyun (FY)-3C satellite measure the outgoing radiance form the Earth surface and atmospheric constituents. MWHTS makes measurements in the isolated oxygen absorption line near 118 GHz and the vicinity of strong water vapor line around 183 GHz, can provide fine vertical distribution structure of both atmospheric humidity and temperature. However, in order to obtain the accurate soundings of humidity and temperature by the physical retrieval method, bias between the observed radiance and those simulated by radiative transfer model from the background or first guess profiles must be correct. In this study, two bias correction methods are developed through the correlation analysis between MWHTS measurements and air mass identified by the first guess profiles of the physical inversion, one is the linear regression correction (LRC) and the other is neural networks correction (NNC), representing the linear and nonlinear nature between MWHTS measurements and air mass, respectively. Both correction methods have been applied to MWHTS observed brightness temperatures over the geographic area (180° W-180° E, 60° S-60° N). The corrected results are evaluated by the probability density function of the difference between corrected observations and simulated values and the root mean square error (RMSE) with respect to simulated observations. The numerical results show that the NNC method perform better, especially in MWHTS channels 1 and 7-9 whose peak weight function heights are close to the surface. In order to assess the effects of bias correction methods proposed in this study on the retrieval accuracy, a one-dimensional variational system was built and applied to the MWHTS uncorrected and corrected brightness temperatures to estimated atmospheric temperature and humidity profiles, The retrieval results show that the NNC has better performance which is to be expected. An indication of the stability and robustness of NNC method is given which suggests that the NNC method has promising application perspectives in the physical retrieval.

Keywords: Porcine reproductive and respiratory syndrome virus, baculovirus surface display vectors, neutralizing antibody, IFN-γ, IL-4.

The advent of immunotherapy has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC), improving the prognosis of this disease and becoming a key part of the treatment, especially in the population without an oncogenic driver mutation. Two different groups of immune checkpoint inhibitors (ICIs) are used in lung cancer: Anti- Cytotoxic T-lymphocyte antigen-4 (Anti-CTLA 4) and Anti- T-cell receptor programmed cell death-1 or its ligand (Anti-PD-1 and Anti PD-L1). Here in, we review an uptodate on the use of immunotherapy for advanced NSCLC.

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

Immunotherapy has been considered for years as a viable and attractive treatment option for patients with cancer. Among immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionized the treatment of several subtypes of tumours. These approaches aimed at restoring an effective anti-tumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells, and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed-death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because in these diseases the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and will build a projection of how the field may evolve in the near future. In particular, we will analyze the current strategies being evaluated both preclinically and clinically with the aim to foster the use of immune-checkpoint inhibitors in non-Hodgkin lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies.

In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) might prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production by the liver. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry and important biological function, e.g., inhibition of GP. Herein, the Suárez radical methodology is successfully applied to synthesize the first example of a 1,6-dioxa-4-azaspiro[4.5]decane system, not been previously constructed via a radical pathway, starting from 6-hydroxymethyl-b-D-glucopyranosyluracil. It is shown that in the rigid pyranosyl conformation the required [1,5]-radical translocation is a minor process. The stereochemistry of the spirocycles obtained was unequivocally determined based on the chemical shifts of key sugar protons in the ¹H NMR spectra. The two spirocycles were found to be modest inhibitors of RMGPb.

The turnover of the RNA molecules is determined by the rates of transcription and RNA degradation. Several methods have been developed to study mRNA turnover since the beginnings of molecular biology. Here we summarize the main methods to measure RNA half-life: transcription inhibition, gene control and metabolic labelling. These methods were used to detect the cellular activity of the mRNAs degradation machinery, including the exo-ribonuclease Xrn1 and the exosome. Less progress has been made in the study of the differential stability of mature RNAs because the different methods have often yielded inconsistent results so that an mRNA considered to be stable can be classified as unstable by another method. Recent advances in the systematic comparison of different method variants in yeast have permitted the identification of the least invasive methodologies that reflect half-lives the most faithfully, which is expected to open the way for a consistent quantitative analysis of the determinants of mRNA stability.

The study aimed to compare the cardiovascular benefits of Omega-3 Polyunsaturated Fatty Acids from fish oil versus krill oil in different forms and dosages. Following PRISMA 2015, data analysis with R software, and databases were searched from 1993 to 2023, (ID PROSPERO: CRD42024502338). Sixty high-quality studies were analyzed, covering various forms of fish oil and krill oil at different dosages (fish oil (ethyl ester-EE, triglyceride-TG, re-esterified triglycerides-rTG, capsules, emulsion-EM); krill oil (phospholipid/free fatty acid-PL/FFA, high concentration phospholipid-HPL, low concentration phospholipid-LPL)). Meta-analysis revealed that krill oil with phospholipid/free fatty acid at doses 2000-2900 mg effectively lowered triglycerides, while fish oil in ethyl ester form at doses above 3000 mg significantly reduced total cholesterol. Fish oil in triglyceride form at doses 2000-2900 mg and other variations positively impacted HDL-C levels. Fish oil in EE form above 3000 mg and triglyceride form below 2000 mg notably reduced LDL-C. However, there was limited effectiveness observed for other interventions. Analysis for LDL-C exhibited publication bias, while other parameters demonstrated reliability (Egger's test). In conclusion, krill oil - PL/FFA, Fish oil - EE above 3000 mg, Fish oil - TG 2000-3000 mg, and fish oil - rTAG 300-1900 mg effectively in reducing heart risk patients.

Secondary acute myeloid leukemia (sAML) is a heterogeneous malignant hematopoietic disease that arises either from an antecedent hematologic disorder (AHD) including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), aplastic anemia (AA), or as a result of exposure to genotoxic chemotherapeutic agents or radiotherapy (therapy related AML, tAML). sAML is diagnosed when the number of blasts is ≥20% in the bone marrow or peripheral blood, and it is characterized by poor prognosis, resistance to therapy and low overall survival rate. With the recent advances in next generation sequencing technologies, our understanding of the molecular events associated with sAML evolution has significantly increased and opened new perspectives for the development of novel therapies. The genetic aberrations that are associated with sAML affect genes involved in processes such as splicing, chromatin modification and genome integrity. Moreover, non-coding RNAs’ emerged as an important contributing factor to leukemogenesis. For decades, the standard treatment for secondary AML has been the 7 + 3 regimen of cytarabine and daunorubicin which prolongs survival for several months, but modifications in either dosage or delivery has significantly extended that time. Apart from traditional chemotherapy, hematopoietic stem cell transplantation, CAR-T cell therapy and small molecule inhibitors have also emerged to treat sAML.

Keywords: Spine surgery 1; Metastatic spinal cord compression 2; Spinal metastasis 3; Cancer treatment.

The hepatitis E virus (HEV) is a zoonotic pathogen with a variety of hosts, including pigs, which act as reservoirs. In industrialized countries, sporadic cases caused by genotype 3, contracted by ingestion of contaminated uncooked or undercooked meat, have been reported. However, in developing countries, HEV infection is mainly dominated by genotype 2 and often associated with poor hygiene conditions and drinking water supplies. In West Africa, HEV infection and its circulation in domestic fauna are very poorly documented. The aim of this study was to assess the presence of HEV in pork sold in Saint-Louis. Meat products were collected between 20 and 25 August 2022 in three location of Saint-Louis region. After purchasing 250 g of sample, we minced 2 g of sample for extraction of total nucleic acids using the Purelink™ Viral DNA/RNA kit and then RT-PCR using the One-Taq™ One-Step RT-PCR kit targeting the HEV ORF2 genomic region. The products obtained were visualized on a 1% agarose gel. Of a total of 74 samples, divided into pork meat (n=65) and pork liver (n=9), 5.4% (n=4) were tested positive for HEV. In both cases, 2 samples were positive, representing a rate of 3.1% and 22.2% for meat and pork liver respectively. All new viral sequences obtained form a monophyletic group within HEV genotype 3. These preliminary results reveal a potential circulation of HEV in the pig population. The high proportion of contamination in the pork liver samples highlights a major risk associated with their consumption.

\abstract{The existence of vorticies is well known in fluid mechanics and particularly in turbulence theory. In the context of the millennium problem of the Clay Institute on the existence (or not) of Global solutions in time of the Periodic Navier Stokes equations (PNS) results are now proposed to confirm that Global solutions do not exist in the general case of PNS defined on $\mathbb{T}^3$. This corresponds to part ($D$) proposition in the Navier Stokes problem as posted by C.Fefferman. Recent work has shown that for the Euler equations defined on the 3-Torus there exists a H\"older continuous solution for the third component of velocity $v_3$ at the center of each cell or cube of the 3-Torus Lattice. It has also been determined that as the kinematic viscosity changes from the corresponding value at $\nu=0$ to the fully viscous case for the Periodic Navier Stokes equations (PNS) at the value $\nu=1$ the solution reaches a peak ($\frac{\partial v_3}{\partial y_3} = 0$ ) in $y_3$. (third component of $\vec{r}=(y_1,y_2,y_3)$ in Cartesian co-ordinates) Here in the viscous case there exists a dipole which is not centered at the center of the cell of the Lattice. This immediately implies that since the dipole by definition has an equal in magnitude positive and negative peak in the third component of velocity, then the dipole Riemann cut-off surface is covered by a closed surface which is the sphere $\|\vec{r}\|=1$ and where a given cell of dimensions $[-1,1]^3$ is circumscribed on a sphere of radius $1$. For such a closed surface containing a dipole it necessarily follows that the flux at the surface of the sphere of $v_3$ wrt to surface normal $\vec{n}$ is zero including at $y_i, i=1\dots 3$ is zero at the points where the surface of sphere touches the cube walls. At the finite time singularity on the sphere a rotation boundary condition is deduced. Here $\frac{\partial v_3}{\partial \vec{n}}= \vec{n}\cdot \nabla v_3$. Also a boundary condition on the sphere shows rotation of sphere. Finally as a result, on the sphere a solution for $v_3$ is obtained which is proven to be H\"older continuous and it is proven that it is possible to extend H\"older continuity on the sphere uniquely to all of the interior of the ball.}

This research provides a computationally efficient numerical tool for predicting 3-D turbulent flows over hydrofoils. It addresses a gap in existing numerical methods by extending the capabilities of the laminar VIScous Vorticity Equation (VISVE) solver to handle 3-D turbulent flow scenarios. The implementation integrates the k − ω SST model into the 3-D VISVE solver using the Finite Volume Method (FVM), extending its capability to handle turbulent flows. The turbulence model is also parallelized to improve computational efficiency. The application of the newly developed model to 3-D hydrofoil cases expands its scope and serves as preparatory work for future rotational propeller applications. Rigorous testing includes a convergence analysis concerning grid numbers and time step sizes, and validation against a Reynolds-Averaged Navier-Stokes (RANS) solver ensures the reliability and accuracy of the enhanced VISVE solver for turbulent flow simulations. The turbulent VISVE solver offers advantages such as reduced computational domain and costs through a vorticity-based approach. Turbulence concentration within boundary layers and free shear flows does not compromise the advantages of the small computational domain. The simplified meshing process, automatically generated by denoting the number of panels on the hydrofoil, makes the solver accessible for researchers and engineers.

Soluble chaperones residing in the endoplasmic reticulum (ER) play vitally important roles in folding and quality control of newly synthesized proteins that transiently pass through the ER en route to their final destinations. These soluble residents of the ER are themselves endowed with an ER retrieval signal that enables the cell to bring the escaped residents back from the Golgi. Here, by using purified proteins, we showed that Nicotiana tabacum phytaspase, a plant aspartate-specific protease, introduces two breaks at the C-terminus of the N. tabacum ER resident calreticulin-3. These cleavages resulted in removal of either a dipeptide or a hexapeptide from the C-terminus of calreticulin-3 encompassing part or all of the ER retrieval signal. Consistently, expression of the calreticulin-3 derivative mimicking the phytaspase cleavage product in Nicotiana benthamiana cells demonstrated loss of the ER accumulation of the protein. Notably, upon its escape from the ER, calreticulin-3 was further processed by an unknown protease(s) to generate the free N-terminal (N) domain of calreticulin-3, which was ultimately secreted into the apoplast. Our study thus identified a specific proteolytic enzyme capable of precise detachment of the ER retrieval signal from a plant ER resident protein, with implications for the further fate of the escaped resident.

Natural products, especially biologically active compounds derived from plants, have been and continue to be invaluable in anticancer research and therapeutic discoveries. Rice bran arabinoxylan compound (RBAC) is a heteropolysaccharide extract of defatted rice bran obtained through enzymatic treatment with Lentinus Edodes mycelium. RBAC exhibited antitumour properties by arresting in vivo tumour growth in several murine models. In vitro experiments showed RBAC to promote apoptosis in cancer cells by increasing the susceptibility of CD95 (Fas/APO-1) ligands and downregulating Bcl-2 proteins to trigger the permeabilisation of the mitochondrial membrane. RBAC may restore immune dysfunction in cancer patients, most notably by upregulating natural killer cell activity and modulating cytokine production to enhance inflammatory and cytotoxic responses. As such, RBAC acts on the immune system to enhance chemopreventative activity and block tumourigenesis. In treatment, RBAC works synergistically with other natural products and chemotherapeutic agents, such as daunorubicin and paclitaxel, by enhancing drug transport to increase DNA damage in tumours and reduce proliferation. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence, and prolonged survival time. RBAC has been shown to augment the endogenous antioxidant system to prevent oxidative stress and thus protect against the harmful side effects of radiation therapy. RBAC also has chemoprotective effects, with animal and human studies showing reduced toxicity and side effects from chemotherapy, leading to improved health-related quality of life. Meta-analysing the best available evidence indicates that RBAC treatment increases the odds of survival among cancer patients by 4.02 times (95% CI: 1.67, 9.69) in the first year and 2.89 (95% CI: 1.56, 5.35) times in the second year after commencing treatment, compared to those not treated with RBAC. Notwithstanding, additional research is needed to characterise, quantify, and standardise the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to further substantiate the treatment efficacies.

Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein, Neuroligin-3, was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL/6 background. We report that Nlgn3R451C mice show faster gastrointestinal transit in vivo and have longer small intestines compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter and neurally-regulated dysmotility as well as shorter durations of contractile complexes in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent by the GABAA antagonist, gabazine, compared to wild-type mice. Inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum, but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.

The menopausal transition often accompanies distressing manifestations, including vasomotor symptoms, sleep disruptions, and depressive syndrome. Omega-3 fatty acids have emerged as a potential intervention to alleviate these symptoms. This review aimed to comprehensively assess the impact of omega-3 supplementation on vasomotor symptoms, sleep quality, and depression among postmenopausal women. We conducted a systematic search focusing on randomized control trials across the Cochrane Library, Web of Science, PubMed, CINAHL, EMBASE, and SCOPUS databases from inception to August 2023. Among the initial pool of 163 studies, 9 studies met the inclusion criteria and were incorporated into this review. Four studies suggested potential benefits of omega-3 intake for improving hot flashes and night sweats. Sleep quality outcomes displayed heterogeneity across the studies. Incorporating diverse scales such as the Hamilton Depression Rating Scale-21, the Patient Health Questionnaire depression scale, and Generalized Anxiety Disorder-7 for depression outcomes, the review found inconclusive evidence on omega-3's impact on depression. Overall, the combined analysis of these studies did not provide substantial evidence to support the efficacy of omega-3 fatty acids in improving vasomotor symptoms, sleep quality, and depression. Further well-designed RCTs with larger participant groups are crucial to validate and generalize these results.

Coronary artery disease (CAD) is a prevalent cardiovascular condition characterized by the accumulation of plaque within coronary arteries. This plaque accumulation obstructs blood flow to the heart, resulting in a heart attack. While distinct features of CAD have been identified, its causes remain largely unclear, with the exception of environmental and nutritional factors. This study aimed to investigate the connection between genetic factors and CAD, focusing on the thymidylate synthase (TS) gene, a gene involved in one-carbon metabolism. Therefore, our research targeted single nucleotide polymorphisms that could potentially impact TS gene expression and lead to dysfunction. Our findings strongly associate the TS 1100T&gt;C and 1170A&gt;G genotypes with CAD susceptibility. We observed that TS 1100T&gt;C polymorphisms increased disease susceptibility in several groups, while the TS 1170A&gt;G polymorphism displayed a decreasing trend for disease risk when interacting with clinical factors. Furthermore, our results demonstrate the potential contribution of the TS 1100/1170 haplotypes to disease susceptibility, indicating a synergistic interaction with clinical factors in disease occurrence. Based on these findings, we propose that polymorphisms in the 3'-UTR miRNA binding site of the TS gene could serve as clinically useful biomarkers for the prevention, prognosis, and management of CAD.

Rice bran arabinoxylan compound (RBAC) is derived from rice bran enzymatically treated with Lentinus Edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n=37) primary research articles fulfiled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer’s patches. RBAC was shown to promote the innate defence by upregulating the macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC is shown to be a safe and effective neutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC’s bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as an nuetraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods.

This study investigated the effects of modified rice bran arabinoxylan compound (RBAC) as a dietary supplement on the gut microbiota of healthy adults. Ten volunteers supplemented their diet with 1g of RBAC for six weeks and 3g of RBAC for another six weeks, with a three-week washout period. Faecal samples were collected every 3 weeks over 21 weeks. Microbiota from faecal samples were profiled using 16S rRNA sequencing. Assessment of alpha and beta microbiota diversity was performed using the QIIME2 platform. The results revealed that alpha and beta diversity were not associated with the experimental phase, interventional period, RBAC dosage, or time. However, statistical significance of participant was detected in alpha (p&lt;0.002) and beta (weighted unifrac, p=0.001) diversity. Explanatory factors including age and diet were significantly associated with alpha (p&lt;0.05) and beta (p&lt;0.01) diversity. The individual beta diversity of six participants significantly changed (p&lt;0.05) during the interventional period. Seven participants showed statistically significant taxonomic changes (ANCOM W≥5). These results classified four participants as responders to RBAC supplementation, with a further two participants likely responders. In conclusion, the gut microbiome is highly individualised and modulated by RBAC as a dietary supplement, dependent on lifestyle and dietary intake

The Na+/K+ ATPase is a protein involved in the active transport of ions across the cellular membrane. Ouabain is a cardiotonic glycoside that, by inhibiting the Na+/K+ pump, interferes with cell processes mediated directly by the pump, but also indirectly influences other cellular processes, such as cellular cycle and proliferation, growth, cell differentiation, angiogenesis, migration, adhesion and invasion. We used the SK-BR-3 breast cancer cell line, mesenchymal stem cells (MSCs), and tumor-associated fibroblasts (TAFs) in vitro for determining the changes induced by Ouabain in concentration of 10-5 M, 10-6 M, 10-8 M, 10-9 M on these cellular types, employing specific methods: SEM for morphological evaluation; immunocytochemistry, flowcytometry to assess immunophenotypical markers expression, cell cycle and Annexin V/PI assay for cellular proliferation and viability testing; flowchamber assay to evaluate functional adhesion behavior; RT-PCR for Na+/K+ ATPase subunits molecular expression. Being indicative of the pro-apoptotic and inhibitory effect of Ouabain on tumor invasion and metastasis, the results support the addition of Ouabain to the oncological therapeutic arsenal, trailing the “repurposing drugs” approach.

Microglial dysfunction is one of the hallmarks and leading causes of common neurodegenerative diseases (NDD), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). All these pathologies are characterized by aberrant aggregation of disease-causing proteins in the brain, which can directly activate microglia, trigger microglia-mediated neuroinflammation, and increase oxidative stress. Inhibition of glial activation may represent a therapeutic target to alleviate neurodegeneration. Recently, 3-iodothyronamine (T1AM), an endogenous derivative of thyroid hormone (TH) able to interact directly with a specific GPCR known as trace amine-associated receptor 1 (TAAR1), gained interest for its ability to promote neuroprotection in several models. Nevertheless, T1AM’s effects on microglial disfunction remain still elusive. In the present work we investigated whether T1AM could inhibit the inflammatory response of human HMC3 microglial cells to LPS/TNFα or β-amyloid peptide 25-35 (Aβ25-35) stimuli. The results of ELISA and qPCR assays revealed that T1AM was able to reduce microglia-mediate inflammatory response by inhibiting the release of proinflammatory factors, including IL-6, TNFα, NF-kB, MCP1 and MIP1, while promoting the release of anti-inflammatory mediators, such as IL-10. Notably, T1AM anti-inflammatory action in HMC3 cells resulted to be a TAAR1-mediated response, further increasing the relevance of the T1AM/TAAR1 system in the management of NDD.

Accumulating literature demonstrates that omega-3 polyunsaturated fatty acid (N3PUFA) can be incorporated into the phospholipid bilayer of cell membrane in the human body to positively affect the cardiovascular system, including improving epithelial function, decreasing coagulopathy, and attenuating uncontrolled inflammatory responses and oxidative stress. Moreover, it has been proven that the N3PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of some potent endogenous bioactive lipid mediators that mediate some favorable effects attributed to their parent substances. A linear dose-response relationship between increased EPA and DHA intake and reduced thrombotic outcomes have been reported. The excellent safety profile of dietary N3PUFA makes them a prospective adjuvant treatment for people exposed to a higher risk of cardiovascular problems associated with COVID-19. This review presented the potential mechanisms that might contribute to the beneficial effect of N3PUFA and the optimal form and dose applied.

The Surface Urban Heat Island (UHI) is caused by the difference in temperature between the urban and its surrounding areas. However, in the scientific literature, there is no solid methodology defining urban and non-urban areas, which is essential to estimate the SUHI with greater accuracy. This study uses the official national urban areas limit, to obtain the SUHI more accurately on the nine northeastern Brazilian capitals. The land surface temperature was obtained using the Sentinel 3 satellite data for the years 2019 and 2020. Afterward, the maximum and average SUHI, and the complementary indexes were calculated, such as the Urban Thermal Field Variation Index (UTFVI) and the Thermal Discomfort Index (TDI) for the urban areas and their surrounding areas. The Maximum and Average SUHI, obtained values between 1.85 and 8.25 and -4.92 and 2.59 degree difference, respectively, proving the SUHI existence in the study areas. The UTFVI, with values between 0.010 and 0.040, expresses how bad the eco-environmental spaces of urban are. The TDI, with values between 24.61 and 28.89 ºC, expresses the population’s thermal comfort. Therefore, this study provides a better understanding of the surface UHI pioneeringly for the Brazilian Northeast Region.

In recent years, the rise of advanced artificial intelligence technologies has had a profound impact on many fields, including education and research. One such technology is ChatGPT, a powerful large language model developed by OpenAI. This technology offers exciting opportunities for students and educators, including personalized feedback, increased accessibility, interactive conversations, lesson preparation, evaluation, and new ways to teach complex concepts. However, ChatGPT poses different threats to the traditional education and research system, including the possibility of cheating on online exams, human-like text generation, diminished critical thinking skills, and difficulties in evaluating information generated by ChatGPT. This study explores potential opportunities and threats that ChatGPT poses to overall education from the perspective of students and educators. Furthermore, for programming learning, we explore how ChatGPT helps students improve their programming skills. To demonstrate this, we conducted different coding-related experiments with ChatGPT, including code generation from problem descriptions, pseudocode generation of algorithms from texts, and code correction. We also verified the generated codes with an online judge system to evaluate their accuracy.

Background: Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (Dio3) is present in immune cells but there is no description of its presence in this patients. Here we aimed to determine the prognostic impact of thyroid hormones levels (TH) measured on ICU admission on mortality and on evolution to chronic critical illness (CCI) and the presence of D3 in white cells. Methods: Prospective cohort study with a follow-up for 28 days or deceased. Results: Low T3 levels at admission were present in 86.5% of the patients. Dio3 was 55% induced in immune cells. The cut-off value of 60 pg/mL for T3 displayed a sensitivity and specificity of 81% and 64% for predicting death, odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 and 0.75 for mortality and evolution to CCI, respectively, thus displaying better performance than commonly used prognostic scores. Conclusions: We advance in the pathophysiology of low T3 showing induced D3 in immune cells during sepsis. Low T3 levels independently predicted a progression to CCI and mortality within 28 days in sepsis and septic shock.

Enterococcus faecalis is a bacterium that can develop a multidrug resistance profile associated with the community as well as nosocomial-acquired infections. Among the treatment options for these infections are aminoglycosides combined with bacterial cell wall inhibitors such as beta-lactams, since E. faecalis is intrinsically resistant to aminoglycosides. One of its most representative resistance mechanisms is the expression of aminoglycoside-modifying enzymes, such as the aminoglycoside phosphotransferase type IIIa of E. faecalis (EfAPH(3')-IIIa). This enzyme acts by phosphorylating aminoglycosides in an ATP-dependent reaction, modifying the 3' position of hydroxyl groups of these antibiotics. Considering this scenario, 3,092 natural products obtained from the ZINC22 database were analyzed to select molecules with the highest affinity for the nucleotide-binding pocket of EfAPH(3')-IIIa, which could be potential aminoglycoside adjuvants. The molecules that showed the best-score results obtained from ensemble docking-based virtual screening were ZINC000000952700 (BS-1), ZINC000014793040 (BS-2) and ZINC000015498603 (BS-3). The most promising results were for BS-2, a flavone derivative, due to its improved stability profile in molecular dynamics simulation (average values of RMSD of 0.23 nm, and Rg of 1.94 nm), binding free energy calculations (average ΔG total of -35.3 nm), as well as better toxicological profile (lower probability of hepatotoxicity, carcinogenic, immunotoxicity, mutagenicity, and cytotoxicity effects), compared to BS-1 and BS-3. These results allow us to propose that a flavone derivative may act as an adjuvant to aminoglycosides in the treatment of E. faecalis infections, acting as an inhibitor in the nucleotide-binding pocket of EfAPH(3')-IIIa.

The problem of fluid dynamics can be greatly simplified if, for every point in space, the strain-rate tensor is diagonalized. This tensor is introduced into the Navier-Stokes equations via material law and divergence of the stress tensor. This article shows that local SO(3)xU(1) gauge fields can be used to locally diagonalize the diffusion components of the strain-rate tensor. The gauge fields resulting from the connection can be interpreted as convection components of the flow, they show properties of quasiparticles and can be interpreted as elementary vortices. Thus, the proposed approach not only offers new insights for the solution and situative simplification of the Navier-Stokes equations, it also uncovers hidden symmetries within the flow convection, allowing - depending on boundary conditions - further interpretation.