Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

Two new zoanthamine alkaloids, namely 3-acetoxynorzoanthamine (1) and 3-acetoxyzoanthamine (2), have been isolated from the zoantharian Zoanthus cf. pulchellus collected off the coast of the Peninsula of Santa Elena – Ecuador, together with three known alkaloids zoanthamine, norzoanthamine and 3-hydroxynorzoanthamine. The chemical structures of 1 and 2 were determined by interpretation of their 1D and 2D NMR data and comparison with literature data. This is the first report of zoanthamine-type alkaloids from Zoanthus cf. pulchellus collected in the Tropical Eastern Pacific. The neuroinflammatory activity of all the isolated compounds were evaluated in microglia BV-2 cells and high inhibitory effects were observed in ROS and NO generation.

Chitosan is a biodegradable polymer derived from chitin, that is a versatile material for various biological applications for its attractive properties such as biocompatibility, biodegradability, and non-toxicity. Furthermore, chitosan possesses Second Harmonic Generation properties, that are useful for bio-sensing applications. In this work we explored the possibility to exploit chitosan-based nanospheres as SHG-based bio-sensors, and also as carriers of 89Sr radionuclide, an Active Pharmaceutical Ingredient for radiopharmaceutical treatments in cancer therapy. To load opportunely the Sr ion on the nanospheres, we used a fructose-based Metal Organic Framework, of formula [Sr(C6H12O6)2(H2O)2]Cl2·H2O, because the sugar was able to drive the Sr ions on the chitosan matrix. The Sr-loaded chitosan nanospheres were synthetized, characterized, and their SHG response was measured. The results encouraged us to propose the nanospheres for theranostic purposes, i.e. at the same time valuable for both therapy and diagnostic applications.

Biochar is a carbon-rich material that recently received attention due to its increasing agronomical potential. The agricultural utilization of biochar relates to its potential to act in the soil as a soil conditioner, nevertheless, the complex information on the direct dependence of biochar physical properties (texture, particle size) and corresponding leaching and availability of organic molecules (e.g. the polycyclic and heterocyclic organic compounds) and inorganic mineral salts (based on micro– and macroelements) are still not consistent. These aspects were addressed in our study. A multi-elemental analysis (ICP-OES) was used to access the information on the aqueous-extractable and total contents of inorganic macro- and macroelements in used commercial biochar samples (purchased from Sonnenerde GmbH, Novoterrra Sonnenerde GmbH, Biouhel.cz, s.r.o.). Potassium (K) was identified as the major macroelement, responsible for alkaline pH and the conductivity of biochar extract. Our results indicate an indirect relation between the size fraction of biochar and the content of extractable K, sodium (Na), and calcium (Ca) and a direct relation with the contents of phosphorus (P) and magnesium (Mg). As the total determined amounts of inorganic elements were significantly higher compared to aqueous-extractable amounts, we believe it could indicate the potential for repeated release to the surrounding soil. These findings were also confirmed by the analysis of biochar samples obtained after the cultivation (duration of 2 years) in selected representative soil samples from the Czech Republic (Cambisol, Fluvisol, Regosol, Chernozem). Moreover, gas chromatography (GC) coupled with mass spectroscopy (MS) was further used to reveal the concentrations of available polycyclic aromatic and heterocyclic compounds in biochar samples. The detected concentration of these types of organic compounds were far below the certified limits. We believe our in-depth analysis could provide the necessary insight into the description of biochar mineral content, its connection to biochar texture, corresponding physicochemical properties and potential availability to leach nutrients to the soil. These findings could help in further assessment of the potential applications of biochar in modern agriculture as a soil conditioner.

: Organic poultry need high-quality proteins in their diet. The EU’s organic regulation forbids synthetic amino acids; therefore, soybean, with its balanced essential amino acid content, has become the most used protein source, though much of it is imported from non-EU countries. Soybean, however, has some important problems related to sustainability and crop competition; therefore, it must be substituted with a high-protein-value alternative such as insect meal. In this study, 900 Aviagen Savanna broilers were reared using three different organic diets. The diets used the following as protein feed material: soybean only (S100), 50% black soldier fly larvae meal (BSL) and 50% soybean (BSL50), and 100% BSL only (BSL100). Broiler performance, welfare, and fatty acids (FA) in the thigh and breast were analyzed. BSL50 and BSL100 negatively affected growth performance, while BSL100 worsened all of the market-related measures of performance. Meat quality was worse in BSL50 and BSL100, with a significant increase in saturated FA (SFA) and a corresponding decrease in polyunsaturated FA (PUFA). Among SFA, lauric acid (C12:0) more notably increased. The increase in SFA represents a negative aspect of BSL meal inclusion, namely the production of lauric acid; however, this trend could have a beneficial effect, which will be more deeply explored with regard to its impact on animal and human health.

Obesity affects nearly 660 million adults worldwide and is known for its many comorbidities. Although the phenomenon of obesity is not fully understood, science regularly reveals new determinants of this pathology. Among them, the persistent organic pollutants (POPs) have been recently highlighted. Mainly lipophilic, POPs are normally stored in adipose tissue and can lead to adverse metabolic effects when released into the bloodstream. The main objective of this narrative review is to discuss the different pathways by which physical activity may counteract POPs adverse effects. The research that we carried out seems to indicate that physical activity could positively influence several pathways negatively influenced by POPs, such as insulin resistance, inflammation, lipid accumulation, adipogenesis and gut microbiota dysbiosis that are associated with the development of obesity. This review also indicates how, through the controlled mobilization of POPs, physical activity could be a valuable approach to reduce the concentration of POPs in the bloodstream. These findings suggest that physical activity should be used to counteract the adverse effects of POPs. However, future studies should accurately assess its impact in specific situations such as bariatric surgery where weight loss promotes POPs blood release.

In order to investigate both the physiological and molecular mechanisms underlying the impacts of organic selenium and nano-selenium on drought stress of Pak Choi (Brassica chinensis var. pekinensis. cv. ‘Suzhouqing’), we measured photosynthetic pigment, antioxidant, nutritional quality, and performed transcriptome sequencing of leaves using RNA-seq technology. Under drought conditions, the beneficial effects of organic selenium and nano-selenium on weight and quality of ‘Suzhouqing’ were primarily manifested in the following aspects. Firstly, there was an enhancement in photosynthetic capacity through upregulation of light-trapping pigment proteins: Lhca1, Lhca2, Lhca3, Lhca4, Lhcb1, Lhcb2, Lhcb3, Lhcb4 and Lhcb5. Secondly, effective regulation of reactive oxygen species homeostasis was achieved by activating the antioxidant system via up-regulation of glutathione S-transferase. Thirdly, water homeostasis was maintained through glutathione oxidase activity. Lastly, increased expression levels of ABC transporter, adenylate kinase and cysteine desulphurase contributed to elevated total selenium content. In addition, we screened hub core genes related to the above key metabolic pathways through Weighted Gene Co-expression Network Analysis. Since the results were consistent with the up-regulated genes identified in the Kyoto Encyclopedia of Genes and Genomes pathway of differentially expressed genes by transcriptome sequencing analysis, this confirms the accuracy and reliability of the transcriptome sequencing data.

In recent years, frequent occurrences of low temperature disasters due to global climate change have significantly impacted the normal growth of crops. Research has indicated that inorganic selenium (which is more toxic) can not only enhance the effects of low temperature stress but also increase selenium content on plants; however, there is a scarcity of studies investigating the impacts of organic selenium and nano-selenium on crops. In order to investigate whether organic selenium and nano-selenium can enhance low-temperature tolerance and increase selenium content in pak choi (Brassica chinensis var. pekinensis. cv. ‘Suzhouqing’), different concentrations (0, 5, 10, 20 mg L-1) of exogenous selenium were applied in this experiment to assess their effects on plant growth, nutritional quality and antioxidant properties. RNA-Seq technology was used to sequence the transcriptome of the leaves. Based on the transcriptome data, a Weighted Gene Co-expression Network Analysis (WGCNA) was employed to construct a network that associates with physiological traits related to stress resistance. Two highly correlated gene co-expression modules were identified, and within them, nine hub genes associated with endocytosis, antioxidant stress, absorption, transport, and metabolism of selenium were discovered. The results indicated that the beneficial effects on yield and total selenium content under low temperature were attributed to (1) protection of photosynthetic pigments for enhancing photosynthetic capacity by the up-regulation of LHca2, LHcb1, LHca1, LHcb4 in KEGG pathway: photosynthesis-antenna proteins; (2) activation of antioxidant system for efficient ROS homeostasis such as SOD, POD and CAT by the genes such as Superoxide dismutase, Monodehydroascorbate and (3) selenium absorption by endocytosis, seleninum transportation by ABC transporter gene family and selenium metabolism related genes such as Cysteine synthase, Glutaredoxin. These findings provide a foundation for further investigation into the molecular mechanisms underlying the effects of organic selenium and nano-selenium on cyanochloride production at low temperatures.

The application of organic fertilizers plays a crucial role in achieving carbon sequestration in the agricultural sector. This paper discusses how farmers can more smoothly promote organic fertilizer extension services. An evolutionary game model is developed to describe the conflicting interests of Chinese farmers and local governments in organic fertilizer extension services, and the dynamic evolution of the game players and the influence of parameter adjustment on the strategic choices of both parties is presented. In this paper, the game model and the main results are validated with the help of simulation tools, and a sensitivity analysis of the selected parameters is performed. The results show that (1) the implementation of subsidy policy is less helpful for organic fertilizer extension services; (2) The ideal event probability of the game was found to be positively related to the cost of applying inorganic fertilizers, additional benefits to farmers, political returns to local governments, and penalties for not using organic fertilizers; (3) This is important for improving the performance of local governments, reducing government regulatory costs, improving policy support for organic fertilizer extension services, and reducing the cost of implementing organic fertilizer extension services.

Organic carbon (OC) accumulation in soil mitigates greenhouse gases emission and improves soil health. We aimed to quantify the dynamics of OC stock in soils and to justify technologies that allow annual increasing OC stock in the arable soil layer by 4‰. We based the study on a field experiment established in 1936 in the 9-field crop rotation with a fallow on Chernozem in European Russia. The RothC version 26.3 was used for the reproducing and forecasting OC dynamics. In all fertilizer applications at FYM background, there was a decrease in the OC stock with preferable loss of active OC, except the period 1964-71 with 2-5‰ annual OC increase. The model estimated the annual C input in the arable soil layer as 1,900 kg·ha-1. For increasing OC stocks by 4‰ per year, one should raise input to 2400 kg·ha-1. Simulation was made for 2016-2090 using climate scenarios RCP4.5 and RCP8.5. Crop rotation without fallowing provided an initial increase of 3‰ and 6‰ of stocks in the RCP8.5 and RCP4.5 scenarios accordingly, followed by a loss in accumulated OC. Simulation demonstrates difficulties to increase OC concentration in Chernozems under intensive farming and potential capacity to rise OC stock through yield management.

The aim of the present study was to assess the efficacy of All Cosmos Industries (ACI) bio-organic and bio-chemical fertilizers and ACI N-Fixer (N-Bio Booster) on the paddy yields based on the field trial plots at Langkat, Medan, Indonesia. This application of ACI bio-organic fertilizer (NPK 5/5/5) and ACI bio-chemical (NPK 15/15/15) fertilizer and ACI N-Fixer tests were conducted at the paddy farm at Langkat from May-October 2018. This study employed a factorial randomized complete block design which consisted of two factors, namely: Factor I with four types of fertilizers while Factor II consisted of two paddy varieties (Inpari 30 and Inpari 32). Overall, the filled grains in the ACI treatments are significantly (P< 0.05) higher than those in the control treatments that used Normal Chemical Compound NPK. Overall, total weight per meter² (368-617g) in ACI treatments are also significantly (P< 0.05) higher than those (319-371g) in the control treatments. At harvesting time at 105 days after transplanting, significantly higher (P< 0.05) colony counts (13-15 x 10⁶ CFU/mL) (for ACI treatments), than those (8 x 10⁶ CFU/mL) in the controls positively indicated higher total yields of paddy grains per hectare. It was found that the application of ACI bio-organic and bio-chemical fertilizers and ACI N-Fixer can improve paddy yields of the two rice varieties, between 16.4-38.2% (up to 5.75 MT/ha), in the field trial plots at Langkat. These commercial fertilizers play an imperative role in refining the soil fertility and thereby can increase the yield of rice production. Therefore, it is highly recommended that ACI bio-organic and ACI bio-chemical fertilizers and ACI N-Fixer (N-Bio Booster) can be employed to increase the paddy yield in this region.

The chlorophyll is one of the most important natural pigments used extensively in the food industry. Two important factors for the production of chlorophyll are the use of plants rich in chlorophyll and efficiency of extraction method. Present investigation was performed to compare the extraction of photosynthetic pigments by using solvents of different chemical nature. The purslane plants with different growth behavior viz. Scrollable and standing were grown under shade and sunshine stress condition. Different solvents including diethyl ether, 5% ethanol, pure acetone, 20% acetone, pure methanol and 10% methanol were used to extract chlorophyll and carotenoids from the purslane plant. The results indicated that stress, growth type and different solvents had a significant effect on the extraction of chlorophyll and carotenoids. Different trend was observed in extraction rate for chlorophylls and carotenoids. Among the solvents, pure methanol was the best for extraction of chl a. Methanol and acetone were appropriate solvents to achieve the highest amount of chlorophyll from plant tissues. Among different solvents, pure methanol for chl a, pure acetone and methanol for carotenoids were best solvent for purslane plant with a growing type scrollable of under shade.

PgRMC1 (progesterone receptor membrane component 1) is a progesterone-binding protein highly expressed in various cancer cells. Its expression has been associated with cancer development, chemoresistance, and poor prognosis in breast cancer through the regulation of drug and sterol metabolism, cell cycle, and apoptosis. However, the precise functions of PgRMC1 remain unclear. We examined PgRMC1 expression in breast cancer tissues and analyzed its correlation with clinicopathological characteristics and treatment response (n=112). PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity for PgRMC1 was observed in normal breast tissue. Notably, PgRMC1 expression levels were high in the HER2 subtype. Among patients treated with neoadjuvant chemotherapy, those with a poor pathological response had significantly higher PgRMC1 expression than those with a good response. PgRMC1 overexpression in breast cancer cell lines reduced chemosensitivity. Real-time qPCR analyses revealed that PgRMC1 induced the expression of differentiation markers, including CDH1 and KRT19, indicating that PgRMC1 is involved in the suppression of epithelial-mesenchymal transition and mammary luminal epithelial differentiation. Our findings suggest that PgRMC1 may contribute to chemoresistance and serve as a putative biomarker for assessing neoadjuvant chemotherapy sensitivity.

The bulk planetary compositions are thought to be linked to the chemical abundances of their host stars. The abundances of 8 key rock-forming elements and the key planetary abundance ratios in G– and F–type main sequence stars located in the Solar neighborhood within 50 pc were statistically analyzed. The averaged C/O, Mg/Si, and Fe/Si elemental ratios of the planetary systems have a crucial role in the chemical composition and the mineralogy of a rocky planet's interior. We also studied the variation of the calculated Ca/Si, Al/Si, Na/Si and Fe/Si ratios in the samples of the examined stars using the Ca, Al, Na, and Fe abundances from the catalog and then attempt to constitute plausible occurrence trends of the analyzed abundance ratios for the rocky planet population in the near – solar galactocentric distances. Considering these results, we provide simple predictions for the most likely bulk compositions of the potential rocky planets. We further apply our results to compare them to the solar averaged abundance ratios, finding that the key elemental ratios for rocky planet composition in the Solar System are not typical amongst most of the studied stellar samples.

This study evaluated the effect of pig diet supplementation with an Olea europaea L. extract on the muscle fatty acid composition. Ten commercial hybrid pigs (Large White x (Landrace x Duroc)) were randomly assigned to two experimental treatments and fed either a standard diet (C) or diet with olive leaves extract (OL). For 90 days, the OL group received the olive leaf extract (300 mg/head/day), which mainly comprises oleuropein diglucoside, luteolin-7-glucoside, and verbascoside. The phenolic content, antioxidant activity, bioactive molecules’ characterization, and the fatty acids profile of meat and diet were performed. The results indicated that while the OL supplementation did not significantly alter the overall chemical composition of the meat or the pigs' performance, it did modify the lipid profile of the meat. The OL diet results in a significant reduction in SFA and an increase in oleic acid in meat, which correspondingly elevates the total MUFA content. Dietary treatment reduced the sum of n-6 PUFA in the meat of the OL group, and resulted in a significantly lower n-6/n-3 PUFA ratio. Therefore, these findings suggest that incorporating olive leaf extract into the pig diet enhances the nutritional and functional quality of the meat by improving its fatty acid profile.

A new quinazolinone alkaloid, named peniquinazolinone A (1), as well as eleven known com-pounds, 2-(2-hydroxy-3-phenylpropionamido)-N-methylbenzamide (2), viridicatin (3), viridicatol (4), (±)-cyclopeptin (5a/5b), dehydrocyclopeptin (6), cyclopenin (7), cyclopenol (8), methyl-indole-3-carboxylate (9), 2,5-dihydroxyphenyl acetate (10), methyl m-hydroxyphenylacetate (11), conidiogenone B (12), was isolated from the endophytic Penicillium sp. HJT-A-6. The chemical structures of all compounds were elucidated by comprehensive spectroscopic analysis, including 1D, 2D NMR, and HRESIMS. The absolute configuration at C-13 of peniquinazolinone A (1) was established by applying the modified Mosher’s method. Compounds 2, 3, and 7 exhibited an op-timal promoting effect on the seed germination of Rhodiola tibetica at a concentration of 0.01 mg/mL, while the optimal concentration for compounds 4 and 9 to promote Rhodiola tibetica seed germination was 0.001 mg/mL. Compound 12 showed optimal seed-germination-promoting activity at a concentration of 0.1 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compounds 2, 3, 4, 7, 9, and 12 could extend the seed-germination period of Rhodiola tibetica up to the 11th day.

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. Cucumerinum (Foc) of cucumber is a destructive soil-borne disease in cucumber (Cucumis sativus.L). There is limited knowledge on molecular mechanisms to FW resistance-mediated defense responses in cucumber. In this study, metabolome and transcriptome profiling were carried out in two FW, resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. The NILs showed consistent and stable FW resistances in multiple greenhouse and laboratory screening tests. Widely targeted metabolomic analysis identified differentially accumulated metabolites (DMAs) with significantly more accumulation in NR in response to Foc infection including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway. Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis in or transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NR-conferred FW resistance was exemplified by in vivo assays in which two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, and the flavonoid compound gallocatechin 3-O-gallate were shown to have significant inhibitory effect on Foc growth. The antifungal effect of three compounds seems to be a novel finding. We conclude that phenolic acids and flavonoids play an important role in NR mediated FW resistance in cucumber.

Plant-based proteins, like those derived from hemp and rapeseed can significantly contribute to a balanced diet and human daily nutritional requirements by providing essential nutrients such as protein, fiber, vitamins, minerals, and antioxidants. According to numerous recent research papers the consumption of plant-based proteins has been associated with numerous health benefits, including reduced risk of chronic diseases such as heart disease, diabetes, and certain cancers. Plant-based diets are often lower in saturated fat and cholesterol and higher in fiber and phytonutrients, which can support overall health and well-being. Present research investigates the nutritional attributes, functional properties, and potential food applications of hemp and rapeseed protein for a potential use in new food product development, with a certain focus on identifying anti-nutritional factors and bioactive compounds. Through comprehensive analysis, anti-nutritional factors and bioactive compounds were elucidated, shedding light on their impact on protein quality and digestibility. The study also delves into the functional properties of hemp and rapeseed protein, unveiling their versatility in various food applications. Insights from this research contribute to a deeper understanding of the nutritional value and functional potential of hemp and rapeseed protein, paving the way for their further utilization in innovative food products with enhanced nutritional value and notable health benefits.

Seventeen bacterial strains able to suppress plant pathogens have been isolated from healthy Vietnamese crop plants, and taxonomically assigned as members of the Bacillus cereus group. In order to prove their potential as biocontrol agents, we performed a comprehensive analysis which included whole genome sequencing of selected strains, and mining for genes and gene clusters involved in the synthesis of endo- and exotoxins, and secondary metabolites, such as antimicrobial peptides (AMPs). Kurstakin, thumolycin, and other AMPs were detected and characterized by different mass spectrometric methods, such as MALDI-TOF-MS, and LIFT-MALDI-TOF/TOF fragment analysis. Based on their whole genome sequences, the plant-associated isolates were assigned to the following species and subspecies: B. cereus subsp. cereus (6), B. cereus subsp. bombysepticus (5), Bacillus tropicus (2), and Bacillus pacificus. Three isolates represented novel genomospecies. Genes encoding entomopathogenic crystal and vegetative proteins were detected in B. cereus subsp. bombysepticus TK1. In vitro assays revealed that many plant-associated isolates enhanced plant growth and suppressed plant pathogens. Our findings indicated that plant-associated representatives of the B. cereus group are a rich source of putative antimicrobial compounds with potential in sustainable agriculture. However, the presence of virulence genes might restrict their application as biologicals in agriculture.

There were designed and synthesized two new sulfone 2-aminobenzimidazole derivatives. Coordination compounds were obtained with nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) and these novel ligands. There were fully characterized by spectroscopic and analytical techniques. Single crystal X-ray structural analysis was performed on order to study the relevant intra and inter non-covalent interactions, mainly H...π, lone pair·...π, π...π, highlighting the difference between the ethyl and phenyl groups in such interactions. Dimeric and trimeric supramolecular syntons were found for some of these compounds. Their biological activity was investigated, being the copper(II) compounds with the sulfone phenyl derivative the most active.

Leishmaniasis is a neglected tropical disease and affects more than 350 million people worldwide. However, there are no vaccines for humans, and current treatment is hampered due to its high cost, numerous side effects, and painful administration routes. Ending its epidemics by 2030 has become a United Nations goal, and the multitarget drug strategy emerges as a promising alternative. Flavonoids are an example of multitarget compounds and organic synthesis represents a tool to obtain high yields of these molecules. In our study, we synthesized 17 flavonoid analogs using a scalable, easy-to-reproduce, and inexpensive method. All compounds demonstrated an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b stood out as effective against all isoforms and intermolecular interactions were investigated through a molecular modeling study. The compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. The results were pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Furthermore, compounds have shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases.

Lipophilicity can be measured with different methods, such as Shake-Flask or liquid chromatography. HPLC presents the advantage of overcoming solubility issues and therefore extending the range of lipophilicity to high values. A specific HPLC method, called ELogD, had been developed 20 years ago on a C₁₆-amide stationary phase, enhancing hydrophobic and hydrogen bond interactions to mimic octanol-water partition. The emergence of novel stationary phases added to the need for a less complex mobile phase has led to the development of a new HPLC assay called alphaLogD, applicable to neutral and basic compounds at pH 7.4, that combines superficially porous particles, a high number of equilibriums between solutes and stationary phase, and results in a lower number of isocratic methods to determine the logk’_w at a higher throughput. Statistical studies have been run to successfully evaluate the alphaLogD method compared to the Shake-Flask method and to allow this lipophilicity measurement into the so-called Beyond-Rule-of-5-molecules space.

Gymnema sylvestre is a pharmacological plant which has a rich source of bioactive compounds specifically gymnemic acid (GA) and phenolic compounds (PC) that used for pharmaceutical industries. Sources for naturally occurring bioactive compounds are limited, due to geographical and seasonal variations; on the other hand, it is commercially in demand. Biosynthesis of G. sylvestre phytochemicals through in vitro culture often enhanced by elicitation. The use of cell suspension cultures (CSC) has interested serious attention on the production of essential phytochemicals. The current study is aimed at improving the contents of GA and PC in G. sylvestre CSC using the copper oxide nanoparticles (CuO NPs). Callus was obtained on MS medium with 2.0 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), 0.1 mg/L kinetin (KIN), phytoagar (8.0 g/L), and sucrose (30 g/L). The above medium devoid of agar was used for the initiation of CSC. The CSC was treated with three levels of CuO NPs (1, 3 or 5 mg/L) to enhance the production of GA and PC. The greatest amount of GA (89.25 mg/g dry cell mass, DCM), total phenolic (245.10 mg/g), and flavonoid (4.57 mg/g) in CSC were achieved when G. sylvestre cells were treated for 48 h with 3 mg/L CuO NPs. Also, the biomedical potential (antioxidant, antidiabetic, anti-inflammatory, antibacterial, antifungal and anticancer activities) were also high in the CuO NPs (3 mg/L) treated CSC extracts of G. sylvestre. CuO NPs elicitation of CSC significantly increased production of GA (9-fold), and PC than non-elicited CSC in G. sylvestre.

Catalyst material plays a pivotal role in the pharmaceutical industry process. Among them, Friedel-Craft acylation reaction is a well-known reaction to synthesis acetophenone derivatives. However, Friedel-Craft acylation mostly used acetyl chloride as starting material with Lewis acid as homogeneous catalyst, which is nonenvironmental friendly process. In this work, a simple and efficient Friedel-Craft acylation reaction is reported by using the palladium oxide doped on activated bentonite (PdOAB) as the heterogeneous catalyst. The PdOAB catalyst material was characterized with scanning electron microscopy-energy dispersive X-ray (SEM-EDX), nitrogen isotherm adsorption, Fourier transform infrared (FTIR), X-ray powder diffraction (XRD), and thermogravimetric-differential thermal analysis (TG-DTA). The acetophenone derivatives with R = -H, -Cl, -CH₃, -OCH₃, -OH and -NH₂ at para position were successfully synthesized from its corresponding aromatic compounds with glacial acetic acid in 86.6, 7.9, 91.7, 86.6, 82.7, and 78.9% yield, respectively. Therefore, a green method was established because the byproduct is water and the catalyst material can be recovered. Furthermore, the substituent (σ) constants were obtained by using Hammet equation, and the catalysis mechanism has been proposed.

Triazole derivatives of fluorescein containing N,N-dimethylaminopropyl fragments and their ammonium salts were synthesized with yields of 74 - 85%. The resulting compounds exhibit fluorescent properties in the green region of the visible spectrum. The critical aggregation concentration (CAC) was estimated using a py-rene fluorescent probe corresponding to a range of 0.28 - 1.43 mM, and at concentrations above the CAC the compounds form stable aggregates ranging from 165 to 202 nm. A relative quantum yield of 5-24% has been calculated based on fluorescence and UV spectra. The best value is shown by a derivative containing a tetradecyl substituent. When studying the photocatalytic properties of synthesized compounds through the reaction between N-substituted 1,2,3,4-tetrahydroisoquinoline and malonic ester, the mono-tetradecyl deriva-tive demonstrated the best results. According to gas chromatography-mass spectrometry (GC-MS) data, the conversion of the initial heterocycle reached 95%. Therefore, these resulting compounds have the potential to act as an effective photocatalysts.

Seeds from several Ribes taxa were surveyed for phenolic compounds and in vitro antiproliferative activity against HT-29 colorectal cancer cells. Total phenolic compounds were analysed through the Folin-Ciocalteu procedure, while phenolic profiles were analysed by LC coupled to a single mass spectrometer Orbitrap using an electrospray interface (ESI). Antitumor effects were established using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Total phenolics ranged from 11.4 in R. alpinum to 94.8 mg of caffeic acid equivalents (CAE)/g in R. nigrum 'Koksa'. Concerning phenolic compounds, four were hydroxylated benzoic acids, four cinnamic acid derivatives, eight flavonoids, and nine flavonoid glycosides. The growth inhibition against HT-29 cancer cells was exercised much better by R. nigrum 'Koksa' and Ribes 'Erkeeni' (GI50 37 and 42 µg/ml). All Ribes extracts, except R. nigrum 'Hara katarlik', showed higher activity than that of R. rubrum (GI50 at 72 h: 99 µg/ml). Interestingly, the highly bioactive extract from Ribes 'Erkeeni' contains all detected phenolics, while R. nigrum 'Koksa' lacks only populnin. Therefore, the high bioactivity found for such extracts could be due to a synergy due to all detected compounds. This work constitutes a comprehensive action for expanding knowledge on the phenolic profiles and antitumor activity of GLA-rich Ribes seeds.

Four models of Ce(III) complexes with four ligands based on a 1,2,3-triazole derivatives were studied at four DFT levels. The effect of different ligands on the atomic charge value on the cerium ion was analyzed. Several relationships were clearly established between this atomic charge and that of the surrounding atoms, as well as with several geometric parameters of the ligand and with the molecular properties of the Ce(III) complex. The experimental IR and Raman spectra of the newly obtained Ce(III) complex with the (pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylate ligand were interpreted based on their comparison to the theoretical scaled ones using the scaling equations determined by two procedures and four DFT levels. Therefore, the structure predicted for the synthesized Ce(III) complex was clearly characterized and confirmed. The potential antioxidant action of Ce(III) complex was elucidated and compared with other Ln(III) complexes in order to find out the differences in their biological activity profiles.

Treatment-emergent sexual dysfunction (TESD) is one of the most frequent and persistent adverse effects of antidepressant medication. Sexual dysfunction (SD) secondary to SSRIs occurs in >60% of sexually active patients and >80% of healthy volunteers, with this causing treatment discontinuation in >35% of patients. However, this factor is rarely addressed in routine examinations, and only 15%-30% of these events are spontaneously reported. A strategy of switching to a different non-serotonergic antidepressant could involve a risk of relapse or clinical worsening due to a lack of serotonergic activity. Vortioxetine appears to have less impact on sexual function due to its multimodal mechanism of action. No studies have been published on the effectiveness of switching to vortioxetine in patients with poorly tolerated long-term antidepressant-related SD at naturalistic settings. Study objectives: To determine the effectiveness of switching to vortioxetine due to SD in a routine clinical practice setting. Methodology: observational pragmatic and naturalistic study to determinate the effectiveness of the switch to vortioxetine (mean dosage 13.11±4.03) in 74 patients aged 43.1 ± 12.65 ( 54% males) at risk of discontinuing treatment due to sexual dysfunction. The SALSEX Scale was applied at two moments: baseline visit and after 3 months of follow-up. Results. The global Sexual Dysfunction (SD) measured with the SALSEX Scale, decreased significantly from baseline visit (10.32; SD 2.73) to follow-up visit (3.78; SD 3.68) p<0.001. There was a significant improvement ( p<0.001) at the endpoint including decreased libido, delay of orgasm, anorgasmia and arousal difficulties in both sexes. After switching to Vortioxetine, 83.81% of patients experienced sexual function improvement (43.2% felt greatly improved). Most patients (83.3%) who switched to vortioxetine continued treatment after the follow-up visit. 58.1% of patients showed an improvement in depressive symptoms from baseline visit. Conclusion. Switching to vortioxetine is an effective and reliable strategy to treat patients with poor tolerated previous antidepressant -related sexual dysfunction in the real-life clinical settings.

Articular cartilage injuries are found in up to 60 % of patients who undergo an arthroscopic knee procedure, those that totally affect articular cartilage (grade IV) have limited regenerative capac-ity and extended time for recovery, 3-D scaffolds represent a novel solution to address this type of injury. Our purpose was to analyze MRI findings and functional status of patients that underwent repair of chondral defects either by microfractures or Hyaluronan (HA) 3-D Scaffold. We con-ducted a retrospective study of patients with chondral defects. The outcomes analyzed in this study included anatomical changes envaulted by the Henderson score (based on MRI findings) at baseline, 6, and 12 months after surgery; and improvement in functionality, evaluated by the Modified Cincinnati Knee Rating System (MCKRS) at baseline and 6 months after surgery. Clini-cal and demographic characteristics were similar for both groups. There was a statistically sig-nificant improvement in Henderson score for the 3-D scaffolding treated group at 6 months, ver-sus the microfracture group (p < 0.0001). Improvement in functionality, measured by MCKRS was more frequently found in the 3-D scaffold treated group. In conclusion the use of HA 3-D scaf-folding was superior with faster recovery, evident after 6 months of the surgery, that progress to full recovery in all patients after a year of surgery. Future studies with a randomized design might help to sustain our findings. This study provides a level III of evidence.

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran (BMBF), a benzofuran derivative, is an intermediate found in the process of total synthesis of ailanthoidol. Benzofuran derivatives are a class of compounds that possess various biological and pharmacological activities. The present study explored the anti-metastasis effects in hepatocellular carcinoma (HCC). Our preliminary findings indicate that BMBF suppresses the proliferation and changes the morphology of Huh7, an HCC cell line with a mutated p53 gene (Y220C). According to scratching motility assay, noncytotoxic concentrations of BMBF significantly inhibited the motility and migration in Huh7 cells. BMBF upregulated the expression of E-cadherin and downregulated the expression of vimentin, Slug, and MMP9, which are associated with epithelial-mesenchymal-transition (EMT) and metastasis in Huh7 cells. BMBF decreased the expression of integrin α7 and deactivated its downstream signal FAK/AKT and inhibited p53 protein levels. Cell transfection with p53 siRNA resulted in prevention of cell invasion because of the reduced expression of integrin α7, Slug, and MMP-9 in Huh7 cells. BMBF had anti-metastatic effects in PLC/PRF/5, an HCC cell line with R249S, a mutated p53 gene. Our findings indicate that BMBF has anti-metastatic effects in that it downregulates p53 and mediates the suppression of integrin α7, EMT, and MMP-9 in HCC cells with mutated p53 gene.

Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.

Controlling Nutritional Status (CONUT) Score is useful for the nutritional screening. We aimed to explore whether the CONUT score may predict a 3-month functional outcome in hemorrhagic stroke (AHS). Totally, 349 patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. Poor functional outcomes were defined as the modified Rankin Scale (mRS) score of ≥ 3 at 3 months. A total of 328 patients (mean age, 60.4 ± 12.83 years; 66.8% male) were included, 172 (52.40%) patients at malnutrition risk and 104 (31.7%) patients with a poor prognosis. High-CONUT patients had lower total lymphocyte counts and total cholesterol levels than low-CONUT patients (p &lt; 0.001 and p = 0.012). At 3-month post discharge, patients with malnutrition risk had higher hospitalization costs (p = 0.021), lower Barthel Index (p = 0.001), and more infectious complications (p = 0.002) than those without, and there was a greater risk for poor functional outcomes in the high-CONUT compared with the low-CONUT patients at admission (adjusted odds ratio: 2.32, 95% confidence interval: 1.28-4.17). High-CONUT scores predict a 3-month poor prognosis in AHS, which may help identify the AHS patients who need additional nutritional managements.

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.

Access to nasopharyngeal swabs for sampling remain a bottleneck in some regions for COVID-19 testing. This study develops a distributed manufacturing solution using only an open source manufacturing tool chain consisting of two types of open source 3-D printing and batch UV curing, and provides a parametric fully free design of a nasopharyngeal swab. The swab was designed using parametric OpenSCAD in two components (a head with engineered break point and various handles), which has several advantages: i) minimizing print time on relatively slow SLA printers, ii) enabling the use of smaller print volume open source SLA printers, iii) reducing the amount of relatively expensive UV resin, and iv) enabling production of handle on more accessible material extrusion 3-D printers. A modular open source UV LED box was designed, fabricated for $45 and tested for batch curing. Swabs can be fabricated for $0.06-$0.12/swab. The results of the mechanical validation tests showed that the swabs could withstand greater forces than would be expected in normal clinical use. The swabs were also able to absorb a significant amounts of synthetic mucus materials and passed abrasion and handling tests. The results show the open source swab are promising candidates for clinical trials.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Prevalence of asthma in Australian children is amongst the highest in the world. Although breastfeeding positively influences infants’ immunity, early introduction of Milk Other than Breast Milk (MOTBM) may also play an important role in the development of Asthma. The aim of this study was to investigate the association between the introduction of MOTBM in the first six months after birth and the development of reported persistent asthma in children 3-years old. As sample of 1,121 children were extracted from the Environments for Healthy Living longitudinal birth cohort study. Introduction of MOTBM during the first six months after birth increased the risk of development of persistent asthma by almost two-folds (Adjusted Relative Risk (ARR): 1.71, 95%CI: 1.03-2.83, p= 0.038). This study indicates that the introduction of MOTBM in the first six months of life is a risk factor for asthma incidence among children 3 years old or younger. This result is important in explaining the benefits of breastfeeding as part of public health interventions to encourage mothers to increase breastfeeding initiation and duration and avoid introduction of MOTBM in the first six months after childbirth.

Nickel nitrate diammine, Ni(NH₃)₂(NO₃)₂, can be synthesised from the thermal decomposition of the nickel nitrate hexammine, Ni[(NH₃)₆](NO₃)₂. The hexammine decomposes in 2 distinct steps; the first releases 4 equivalents of ammonia while the second involves the release of NO_x, N₂ and H₂O to yield NiO. The intermediate diammine compound can be isolated following the first deammoniation step or synthesised as a single phase from the hexammine under vacuum. Powder X-ray diffraction (PXD) experiments have allowed the structure of Ni(NH₃)₂(NO₃)₂ to be solved for the first time. The compound crystallises in orthorhombic space group Pca2₁ (a = 11.0628 (5) Å, b = 6.0454 (3) Å, c = 9.3526 (4) Å; Z = 4) and contains 11 non-hydrogen atoms in the asymmetric unit. Fourier Transform Infrared (FTIR) spectroscopy demonstrates that the bonding in the ammine is consistent with the structure determined by PXD.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Crash prediction of the sharp horizontal curve segment (SHCS) of a freeway is an important tool in analyzing safety of SHCSs and in building a crash prediction model (CPM). The design and crash report data of 88 SHCSs from different institutions were surveyed and three negative binomial (NB) regression models and three generalized negative binomial (GNB) regression models were built to prove that the interactive influence of explanatory variables plays an important role in fitting goodness. The study demonstrates the effective use of the GNB model in analyzing the interactive influence of explanatory variables and in predicting freeway basic segments. Traffic volume, highway horizontal radius, and curve length have been formulated as explanatory variables. Subsequently, we performed statistical analysis to determine the model parameters and conducted sensitivity analysis. Among the six models, the result of model 6, which considered interactive influence, is much better than those of the other models by fitting rules. We also compared the actual results from crashes of 88 SHCSs with those predicted by models 1, 3, and 6. Results demonstrate that model 6 is much more reasonable than models 1 and 3.

Van Wyk Grumbach syndrome refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be done; Here we present a case of a 10-year-old girl with Down syndrome, short stature, and vitiligo presented with vaginal bleeding, and a pelvic mass, in whom bilateral gonadectomy was performed. Most cases of Van Wyk Grumbach syndrome present in women, and classic hypothyroidism symptoms always precede the diagnosis; 11% of patients have Down Syndrome, sometimes tumor markers get elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen sign, pituitary hyperplasia, and severe anemia), that respond to levothyroxine treatment; Conclusions: Children with peripheral precocious puberty and gonadal masses, must be studied for hypothyroidism before any radical decision is made. Keywords: Puberty, Precocious; Ovarian Cysts, gonadectomy, Van Wyk Grumbach Syndrome

Plant-derived compounds have been historically used for the treatment of various diseases and an important source of several clinically useful anti-cancer agents. The Artemisia annua is known as a medicinal herb that is effective against cancer. Thus, the purpose of this study was to investigate whether ethanol extracts of Artemisia annua could increase an anti-cancer effect against LS174T cells. Our results show that Artemisia annua extracts (AAE) induces apoptosis through the regulation of mitochondria outer membrane potential. We demonstrate that apoptosis is induced by p53-dependent manner when cells were treated with Nutlin-3 (MDM2 inhibitor) and LY294002 (Akt inhibitor). In addition, the apoptotic effect was also observed in the p53-independent manner through pifithrin-α (p53 inhibitor) and celecoxib (COX-2 inhibitor) treatment. As in in vitro, AAE induced apoptotic effects and regulated apoptosis-related proteins in LS174T xenograft model. Taken together, these results suggest that Artemisia annua extracts exerts an anti-cancer effect through p53-independent manner, as well as p53-dependent manner by p53´ translocation in LS174T colon cancer cells.

Canine atopic dermatitis (CAD) is a common chronic allergic skin disease. In our previous study, we isolated two probiotic strains, Lactococcus cremoris subsp. cremoris MP01 and Lacticaseibacillus paracasei subsp. paracasei MP02, from Mongolian fermented milk. These strains demonstrated potential in alleviating symptoms similar to AD and reducing specific immunoglobulin E (IgE) levels in a mouse model of AD. Building upon this discovery, our current investigation sought to evaluate the therapeutic potential of these probiotics for treating CAD. We conducted an open-label, single-arm clinical trial where dogs diagnosed with AD were administered LCP capsules containing Lc. cremoris subsp. cremoris MP01 and L. paracasei subsp. paracasei MP02 once daily for 60 days. Stool, skin swab, and venous blood specimens were collected at three intervals: before, and after 30 and 60 days of LCP intervention. The skin and fecal microbiomes were analyzed using full-length 16S rRNA sequencing. After 60 days of LCP intervention, notable improvements were observed in skin lesions and scratching behaviors, accompanied by reductions in both the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and the Pruritus Visual Analogue Scale (PVAS) scores. Additionally, LCP intervention resulted in significant reductions in IgE levels and modulation in type 1 T helper (Th1)/ type 2 T helper cells (Th2)-related cytokine secretion. Microbiota analysis unveiled changes in the composition of both skin and gut microbiotas, including reductions in Shigella flexneri on the skin and Romboutsia in the gut. Levels of short-chain fatty acid (SCFA) increased following the 60-days of LCP intervention. These effects were likely mediated by alterations in gut microbiota and the upregulation of SCFA levels, which subsequently reduced the secretion of allergy-related IgE. Collectively, these mechanisms contributed to alleviating CAD symptoms, regulating skin microbiota composition, and reducing the adherence and invasion of environmental microbes and pathogens. Overall, our findings highlight the promising therapeutic potential of the Lc. cremoris subsp. cremoris MP01 and L. paracasei subsp. paracasei MP02 mixture as an effective strategy for managing CAD in dogs.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

We present a first formal analysis of specific and complete local integration. Complete local integration was previously proposed as a criterion for detecting entities or wholes in distributed dynamical systems. Such entities in turn were conceived to form the basis of a theory of emergence of agents within dynamical systems. Here, we give a more thorough account of the underlying formal measures. The main contribution is the disintegration theorem which reveals a special role of completely locally integrated patterns (what we call ι-entities) within the trajectories they occur in. Apart from proving this theorem we introduce the disintegration hierarchy and its refinement-free version as a way to structure the patterns in a trajectory. Furthermore we construct the least upper bound and provide a candidate for the greatest lower bound of specific local integration. Finally, we calculate the i-entities in small example systems as a first sanity check and find that ι-entities largely fulfil simple expectations.

This study analyzed the anaerobic co-digestion of Inoculum (I), Rubber Plant Effluent (RPE) and Gliricidia leaves (GLS) at different mixing ratios for the simultaneous production of methane and organic fertilizer. The results were analyzed for volatile fatty acids, pH, C/N ratio, and methane production. The organic quality of the substrate mixture before and after anaerobic digestion was analyzed for organic carbon, Kjeldahl nitrogen, potassium, and phosphorus content. The study concluded that the inoculum, Rubber Plant Effluent (RPE), and Gliricidia leaves (GLS) mixed in the ratio of 10:2:2 showed higher methane production than other experiments conducted at different mixing ratios. The nitrogen, Potassium and phosphorus content of the substrates are increased after anaerobic digestion. However, the organic carbon content in the substrate decreased in all experiments. This research recommends the planting of rubber trees and Gliricidia maculata to promote economic development in Mauritania. Keywords: Biogas production; Gliricidia leaves; Methane; Rubber Plant Effluent; Organic Manure

The present research aimed to identify if consumption values influence the attitudes of Millennials who intend to purchase organic products. The research was quantitative, with a correlational scope and a cross-sectional design, and it was conducted on 509 Peruvian millennials. A questionnaire consisting of 23 questions was administered, and responses were quantified using a five-point Likert scale. The results were processed through an Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA), and Structural Equation Modeling (SEM) conducted using Statistical Package for Social Sciences 24 and AMOS 24. The study identified that environmental attitudes of Millennials do influence their intentions to purchase organic products, and the antecedents of these attitudes are functional and social values, whereas emotional, conditional, and epistemic values do not. The study confirmed that consumption values, either as a second-order variable or as a single construct, do not influence the attitudes of Millennials who intend to purchase organic products, thus confirming that these dimensions should be measured independently.

In this study, the gravimetric characterization and analysis of the solubilized extract of the organic fraction of Urban Household Solid Waste (RSDU) from the municipality of Belém do Pará was carried out in order to obtain the composition of the collected materials and the characteristics of the liquid resulting from the solubilization of these materials . The waste used to carry out this research was collected door-to-door, in which the points and neighborhoods served were determined through the sectorization of these locations and representative statistical sampling. For the sectorization of neighborhoods, family income values ​​were considered as the main parameter. After collecting the solid waste, the material was sent to the facilities of the Federal University of Pará (FUPa), where the waste was classified into paper, cardboard, tetrapak, rigid plastic, soft plastic, metals, glass, organic matter, waste toilets, fabrics and others. The organic fraction of solid waste was separated and sent to the drying, crushing and packaging processes. Subsequently, the solubilized extract of the organic fraction of solid waste was obtained, following the methodology recommended by NBR standard nº 10.006/2004, of the Brazilian Association of Technical Standards and the values ​​obtained were compared with Ordinance GM/MS nº 888/2021 and CONAMA Resolution nº 357/2005, in addition to results obtained by other authors. After carrying out the gravimetric characterization, it was possible to obtain the average proportions of 5.09% paper, 3.20% cardboard, 0.94% tetrapak, 3.58% rigid plastic, 9.97% soft plastic, 2.00% metals, 55.57% organic matter, 1.86% glass, 14.26% sanitary waste, 3.23% fabrics and 3.00% other waste. High values ​​of organic residues were found in the gravimetric composition, which can be explained by the collection method used and the high humidity of the organic solid residues. In the analyzes of the solubilized extract, values ​​of Hp (3.69 to 4.92), Turbidity (791 to 1,733 uT), Apparent Color (8,500 to 12,500 uC), True Color (6,000 to 14,000 uC), Total Dissolved Solids (5,330 to 8,040 mg/L), Total Nitrogen (201.80 to 359.90 mg/L), Ammoniacal Nitrogen (161 to 289 mg/L), Nitrate (10 to 40 mg/L), Total Phosphorus (52.30 to 166.80 mg/L) and Chemical Oxygen Demand (28,701 mg/L to 38,608 mg/L), in addition to other measured parameters, in which such information makes it possible to check the similarities of the waste solubilization conditions to that of leachates from landfills, in addition to not being in compliance with environmental and health legislation, demonstrating risks to the local environment and public health.

Herein, we are proposing two chalcone molecules, (E)-1-(4-methoxyphenyl)-3-(p-tolyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl) prop-2-en-1-one, based on the anticancer bioactive molecule Xanthohumol, which are suitable for further in vitro and in vivo studies. Their ability to create stable complexes with the antiapoptotic X-linked IAP (XIAP) protein makes them promising anticancer agents. The calculations were based on ligand-based and structure-based virtual screening combined for the pharmacophore built. Additionally, the structures passed Lipinski's rule for drug use, and their reactivity was confirmed using density functional theory studies. The candidates were chosen between 10639400 compounds, and the docking protocols were evaluated using molecular dynamics simulations.

In this work, the thermodynamic data basis and EOS modeling necessary to simulate the fractionation of organic liquid products (OLP), a liquid reaction product obtained by thermal catalytic cracking of palm oil at 450ºC, 1.0 atmosphere, with 10% (wt.) Na2CO3 as catalyst, in multistage countercurrent absorber/stripping columns using SC-CO2 as solvent, with Aspen-Hysys was systematically investigated. The chemical composition of OLP was used to predict the physical (), thermo-physical properties (Tb, Tc, Pc, Vc), and acentric factor () of all the compounds present in OLP by applying the group contribution methods of Marrero-Gani, Han-Peng, Marrero-Pardillo, Constantinou-Gani, Joback and Reid, and Vetere. The RK-Aspen (EOS) used as thermodynamic fluid package, applied to correlate the experimental phase equilibrium data of binary systems organic liquid products compounds (OLP)-i/CO2 available in the literature. The group contribution methods selected based on the lowest relative average deviation by computing Tb, Tc, Pc, Vc, and . For n-alkanes, the method of Marrero-Gani selected for the prediction of Tc, Pc and Vc, and that of Han-Peng for . For alkenes, the method of Marrero-Gani selected for the prediction of Tb and Tc, Marrero-Pardillo for Pc and Vc, and Han-Peng for . For unsubstituted cyclic hydrocarbons, the method of Constantinou-Gani selected for the prediction of Tb, Marrero-Gani for Tc, Joback for Pc and Vc, and the undirected method of Vetere for . For substituted cyclic hydrocarbons, the method of Constantinou-Gani selected for the prediction of Tb and Pc, Marrero-Gani for Tc and Vc, and the undirected method of Vetere for . For aromatic hydrocarbon, the method of Joback selected for the prediction of Tb, Constantinou-Gani for Tc and Vc, Marrero-Gani for Pc, and the undirected method of Vetere for . The regressions show that RK-Aspen EOS was able to describe the experimental phase equilibrium data for all the binary pairs undecane-CO2, tetradecane-CO2, pentadecane-CO2, hexadecane-CO2, octadecane-CO2, palmitic acid-CO2, and oleic acid-CO2, showing average absolute deviation (AADx) between 0.8% and 1.25% for the liquid phase and (AADy) between 0.01% to 0.66% for gaseous phase.

Faba bean (Vicia faba L) is the first grain legume in terms of hectarage, total production and foreign exchange earnings in Ethiopia. The current study was designed to evaluate effect of NPS and bio-organic fertilizers on the yield and yield components of faba bean in Debre Markos University research farm. A total of 16 treatments were made from the factorial combination of four levels NPS (0, 50, 100 and 150 kg ha-1) and four levels bio-organic fertilizer (Nil BOF (Bio(Nil)), rhizobium (Bio(IR)), 10 t ha-1 FYM (Bio(FYM)) and FYM+Rhizobium (Bio(FYM+IR))) in randomized complete block design (RCBD) with three replications. The Walki (EH 96049-2) variety, which is high yielding, moderate disease resistant and water-logging tolerant used as test crop. The result experiment showed that, plot treated with Bio(FYM+IR)+NPS100 treatment gave statically maximum effective number of tillers (2.73), maximum number of pods per plant (20.30), hundred seeds weight (76.11g), grain yield (5.62 t ha-1), biomass yield (10.94 t ha-1) and Harvest index (59.91%) than over other treatments received NPS fertilizer with and without bio-organic fertilizers. Therefore, the combined use of 100kg ha-1 NPS with 10 tha-1 FYM and rhizobium inoculation is superior for optimum production of faba bean in study area.

I demonstrate that the ionization energy (IE) and the electron affinity (EA) of organic molecular crystals can be predicted from first-principles. Here, I describe the induced electronic polarization and the electrostatic effects upon crystalline IE and EA. I also demonstrate that the electronic polarization mainly originates from the screened coulomb interaction inside the crystalline bulk phase, and that the electrostatic contribution to IE and EA crucially depends on the orientation of the molecule at the surface. The former is well described by the GW approximation, while the latter is reasonably estimated by the difference in frontier orbital energy between the gas phase and the surface at the level of a generalized gradient approximation to the density functional theory. The present methodology enables to demonstrate the impact of the electrostatic effect upon the energy level of the injected charge at a multi-monolayer surface of an organic semiconductor thin film.

Secondary metabolites are bioactive compounds produced by living organisms that can reveal symbiotic relationships in nature. In the work described here, soil-born entomopathogenic-nematodes associated with symbiotic bacteria (Xenorhabdus stockiae and Photorhabdus luminescens) extracted from solvent supernatant containing secondary metabolites showed significant inhibitory action against Escherichia coli, Staphylococcus aureus, Enterococcus faceium, Proteus vulgaris, Bacillus cereus, Bacillus subtilis. These secondary metabolites, characterized by Fourier transform infrared spectroscopy were found to be amine groups of proteins; hydroxyl and carboxyl groups of polyphenols; hydroxyl groups of polysaccharides, and carboxyl groups of organic acids. The major compounds identified by Gas chromatography-mass spectrometry analysis of ethyl acetate extracts of Xenorhabdus stockiae revealed the existence of Nonanoic acid derivatives, Paromycin, Pyrrolidinone, Octodecanal derivatives, Trioxa-5-aza-1-silabicyclo, 4-Octadecenal, Methyl ester, Oleic Acid and 1,2-benzenedicarboxylicacid. Additional extraction from Photorhabdus luminescens was expressed functional compounds such as Indole-3-acetic acid, Piperidinol derivatives, Phthalic acid, 1-Tetradecanol, Nemorosonol, 1-eicosanol and unsaturated fatty acids. These outcomes support the development of new alternative natural antimicrobial agents for pathogen suppression in the future.

(1) Background: Grapes and their associated by-products (as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich egg with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A, and gallic acid were determined; (3) Results: In eggs laid by hens fed GP diet, Haugh units and yolk colour score were enhanced, and eggshell became thinner, but without affecting the breaking strength. No dietary effect was observed on vitamin contents in yolk. Higher gallic acid content was observed in yolk of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness and α- and γ-tocopherol concentration in yolks; (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound, but reduced shell thickness.

Two new coordination compounds of Mn(II) and Cu(II) viz. [Mn(bz)2(Hdmpz)2(H2O)] (1) and [Cu(crot)2(Hdmpz)2] (2) (where, bz = benzoate, crot = crotonate, Hdmpz = 3, 5-dimethyl pyrazole) have been synthesized and characterized using single crystal X-ray diffraction technique, FT-IR, electronic spectroscopy, TGA and elemental analyses. Compounds 1 and 2 crystallize as mono-nuclear coordination compounds of Hdmpz based penta-coordinated Mn(II) and hexa-coordinated Cu(II) respectively containing distorted trigonal bipyramidal and distorted octahedral geome-tries. Crystal structure analysis of compound 1 reveals the presence C‒H⋯π and π-stacking in-teractions along with O‒H⋯O, N‒H⋯O and C‒H⋯O H-bonding interactions which stabilizes the layered assembly of the compound. Similarly, the presence of hydrogen bonding along with π-stacking interactions stabilizes the crystal structure of compound 2. We have carried out theo-retical investigations to analyze π⋯π H-bonding and antiparallel CH···π non-covalent interac-tions observed in the compounds. DFT calculations were performed to evaluate strength of these interactions energetically. Moreover, QTAIM and non-covalent interaction (NCI) plot index computational tool were used to characterize them and evaluate the contribution of the H-bonds.

The study covered the leaves of 25 varieties of highbush blueberry Vaccinium corymbosum L. Determinations were performed for phenolic acid (chlorogenic, neochlorogenic, cryptochlorogenic, 3,5-dicaffeoylquinic and 4,5-dicaffeoylquinic acids), flavonoid (catechin, rutin, isoquercetin), arbutin and hydroquinone content. The content of phenolic acids and flavonoids in the test material suggests that highbush blueberry leaves can be a potentially good material for dietary supplement production, although the relatively high arbutin content (exceeding 4% in the case of the Bonus, Chantiklee and Herbert varieties) limits this possibility to herbal medicinal products applied in case of health issues for a limited time, similar to other over-the-counter arbutin products (bearberry Arctostaphylos uva-ursi and lingonberry Vaccinium vitis-idaea leaves).

This study examined the spatial-temporal distribution of sulfur and iron compounds (dissolved sulfide, iron sulfide, and ionized iron) in sediments from April 2015 to March 2016 at four stations in Mikawa Bay, Japan. Seasonal changes were observed in dissolved sulfide, iron sulfide, and ionized iron in the upper part of the sediment (0–4 cm depth) at all stations. The maximum concentration in the upper part of the central bay was 2.8 mmol L-1. The maximum values of dissolved sulfide (ranging from 1.4 to 8.1 mmol L-1) at stations located in a water way varied among stations. The iron sulfide concentration in the upper part of the sediment at a station where dissolved sulfide concentration in the waterway was relatively low exceeded that at other stations in the waterway during spring to summer. Ionized iron concentration was highest at the station where the dissolved sulfide concentration was low. The study results suggest that iron plays an important role in determining the magnitude of dissolved sulfide accumulation in sediments by binding with dissolved sulfide. The results imply the possibility of mitigating the accumulation of free sulfides, which causes extreme hypoxia, by artificially adding sufficient iron to the seabed.

In this study, five polyphenol compounds (reference substances, ref.) were added to Stokesia laevis (Slae26) ethanolic extract (5 mg GAE / mL) in order to test their antiproliferative effects on human colon tumor cell line Caco-2 (ATCC-HTB-37). The five phenolics (ref.) are luteolin-7-O-glucoside (orientin), luteolin-8-C-glucoside (cinnaroside), caffeic acid, gentisic acid and para-aminobenzoic acid (PABA), and they were combined in ratio 1:1 between the active compounds in samples (GAE : ref.). Results indicated certain antiproliferative effects of Slae26 (IC50=36 μg GAE/mL sample), of the five reference compounds, but mainly of Slae26 combinations with the five phenolics tested (ref.). Punctually, there were obtained IC50 values around 5 μg/mL sample, signifying real therapeutic usefulness and antitumor potency of Slae26 combinations with the five food bioactive compounds tested. In silico docking studies provided potential therapeutic agents to inhibit the catalytic domain of human tankyrase 1 (TNKS1) in the series of food bioactive compounds tested, and revealed luteolin-7-O-glucoside high effectiveness.

Biomimetic compounds are an alternative for to the limited action and fragile nature of enzymes. This work deals with the synthesis, characterization and evaluation of catalytic activity of two new biomimetic models for the active centers of ascorbate oxidase and catalase. [Cu3(S,S(+)cpse)3(H2O)3][Cu3(R,R(-)cpse)3(H2O)3]·17H2O (model for ascorbate oxidase, 1), and [Mn2(S,S(+)Hcpse)4(NaClO4)2(NaOH)(CH4O)]n·[(C2H6O)2]n·[(CH4O)2]n (model for catalase, 2) were prepared through the synchronic method (yields > 78%). The compound 1 has electronic and optical characteristics for racemic compound. The magnetic properties and electrochemical behavior evidence electronic transfer between metal centers. Meanwhile, the compound 2 showed polymeric properties in solid state and dimeric behavior in solution. Compound 1 was able to effectively catalyze the oxidation of ascorbic acid to dehydroascorbic acid (65.6% and 78.24% for racemic and enantiomeric pure compounds) showing structural and functional similarity to the natural enzyme. Besides, Compound 2 catalyzed the decomposition of hydrogen peroxide toward oxygen and water molecules (45%), evidencing that the prepared complex mimics the action of catalases. These two biomimetic models are relationship between them for the structural ligands, the coordination form to metal center and the catalytic activity as oxidase. This research shows the relationship with the design, evaluation, and comprehension of fundamentals aspects for the biomimetic models of active center of metalloenzymes that have importance for biological and industrial processes.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Hybrid reinforcement in a composite material (CM), in many situations, allows better govern material mechanical properties. Polymer matrix CM plate is reinforced with small particles and macro-fibers. Particles are oil shale ash (OSA) powder, macro-fibers – basalt fiber threads im-pregnated by matrix material. With the goal to find out elastic properties of the matrix- polymer with OSA, samples with its different concentrations were experimentally fabricated and their elastic properties were experimentally measured. Obtained data were used in numerical model-ling. Was observed polymer matrix composite slab, reinforced with OSA and three-dimensional (3D) basalt fiber fabric. Fabric are forming threads impregnated by matrix (polymer resin mixed with OSA particles). Damage accumulation in the stretched slab was modelled. Impregnated thread, in the modelling, is observed as a macro-fiber (MF) with averaged elastic properties. With the load increase MF in the material began to break. At first, appeared isolated single breaks. A probabilistic sequential MF rupture accumulation model was accepted and numerical-ly realized. The geometry of the reinforcing knitted fabric was modeled using the Leaf and Glaskin approach. In the knitted fabric highly, stressed MF cross-sections are observed as po-tential location where thread breakage can occur. If one thread breaks, the cross-sections of the adjacent threads experience the overload caused by this rupture. More overloaded crossection in the adjacent overloaded thread breaks and we obtain two adjacent broken MF designated as a defect with the size j=2. The probabilities of obtaining defect consisting of at least 2, 3, … j adjacent broken MF in the plate were calculated. The calculations continued until the rupture process becomes unstable (j→∞). The overstresses on adjacent threads in the CM were calculat-ed using the FEM three-dimensional numerical approach. Analytical and stochastic methods were used for the load-carrying capacity determination and different size defects accumulation in the hybrid composite material (HCM) plate. Also, was calculated the probability of the plate rupture.

This paper addresses the capability to alter the wettability characteristics of poly(vinyl alcohol) (PVA) polymer films doped with glycerol. Films of PVA and glycerol-choline chloride (GCC) blends have been prepared by solution casting method with different glycerol dopants ranging from 0% to 10% (wt %). The results show that as the dopant content increases from 0% to 10%, the wettability increases and hence increases the surface energy of the solid film. The wettability changes are observed by identifying the contact angle of 10 µL deionized water droplet which altered from 55o to 28o as dopant content changed from 0% to 10% per PVA solution weight. The results show that the roughness of film surfaces increases as the content of dopant (GCC) increases in the film which indicates that roughness has a strong influence on the wettability of the casted films.

Although the empirical Kepler’s laws can be proven by applying Newton’s laws to the dynamics of two particles attracted due to the gravitational interaction, there is no explicit formula for the motion as a function of time. In this paper, a quasi-analytical solution for this problem is proposed. It approximates the real behavior of celestial bodies with an acceptable degree of accuracy. All calculations involved require a low computational cost. This problem is closely related to Kepler’s equation, since, the solution for the equations of motion as a function of time gives us the solution to Kepler’s equation as well. The results are presented for each planet of the solar system (including Pluto), and the solution is compared against the real orbits.

Leaf springs are critical components for the railway vehicle safety in which they are installed. Although these components are produced in high-strength alloyed steel and designed to operate under cyclic loading conditions in the high-cyclic fatigue region, their failure is still possible to occur and hence lead to economic and human catastrophes. The aim of this document is precisely to characterise the mechanical crack growth behaviour of the 51CrV4 spring steel representative of leaf springs under cyclic conditions, that is, crack propagation in mode I. The common fatigue crack growth prediction models (Paris and Walker) considering the effect of stress ratio and parameters such as propagation threshold, critical stress intensity factor and crack closure ratio are also determined using statistical methods, which resulted in good approximations with respect to the experimental results. Lastly, the fracture surfaces under the different test conditions were analysed using SEM, with no significant differences to declare. As a result of this research work, it is expected that the developed properties and fatigue crack growth prediction models can assist design and maintenance engineers in understanding fatigue behaviour in the initiation and propagation phase of cracks in leaf springs for railway freight wagons.

A fundamentally new synthetic approach to the synthesis of 2-aminopurine has been developed. It consists in the combination of creation of condensed polyazotic heterocyclic tetrazolopyrimidine structure, it’s transformation into triaminopyrimidine and subsequent cyclization into 2-aminopurine. The structure of the obtained compounds was established based on spectral characteristics and intermediate 5 directly by X-ray diffraction analysis.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

Hybrid biomaterials were engineered using the electrospinning technique, incorporating the dipeptide Boc-L-phenylalanyl-L-Isoleucine into microfibers composed of biocompatible polymers. The examination by scanning electron microscopy affirmed the morphology of the microfibers, exhibiting diameters ranging between 0.9 to 1.8 µm. The dipeptide self-assemblies into spheres with a hydrodynamic size between 0.18 to 1.26 µm. The dielectric properties of these microfibers were characterized through impedance spectroscopy, where variations in both temperature and frequency were systematically studied. The investigation revealed a noteworthy rise in the dielectric constant and AC electric conductivity with increasing temperature, attributable to augmented charge mobility within the material. The successful integration of the dipeptide was substantiated through the observation of Maxwell-Wagner interfacial polarization, affirming the uniform dispersion within the microfibers. In-depth insights into electric permittivity and activation energies were garnered using the Havriliak-Negami model and the AC conductivity behavior. Very importantly, these engineered fibers exhibited pronounced pyroelectric and piezoelectric responses, with Boc-Phe-Ile@PLLA microfibers standing out with the highest piezoelectric coefficient, calculated to be 56 pC/N. These discoveries help us understand how dipeptide nanostructures embedded into electrospun nano/microfibers can greatly affect their pyroelectric and piezoelectric properties. They also point out that polymer fibers could be used as highly efficient piezoelectric energy harvesters, with promising applications in portable and wearable devices.

Forest education is pivotal for achieving the Sustainable Development Goals and promoting sustainable forest management in the face of global challenges. However, existing programs struggle to keep up with rapidly changing crises and uncertainties that contribute to deforestation and forest degradation. To address these challenges, integrating innovative approaches into forest education is crucial. This paper demonstrates the transformative use of a role-playing game as an innovative teaching method for integrated forest management. The game provides students with practical experience and a comprehensive understanding of landscape approaches, using the Congo Basin as a case study. Our research focuses on sustainable forest governance, stakeholder roles, and valuing natural assets and ecosystem services, supporting the transformation of economic, political, and social/cultural relationships at various scales. We highlight the potential of innovative forest education to foster sustainability, trigger critical thinking, resolve conflicts, and prevent costly forest losses.

Background: Human papillomavirus (HPV) is responsible for most cervical cancer cases globally, with women living with HIV at higher risk of persistent HPV infection and HPV-associated disease. The HPV vaccine is a promising solution to reducing cervical cancer rates, but its uptake among women living with HIV in Nigeria is unknown. Methods: A facility-based, cross-sectional survey was conducted with 1,371 women living with HIV to assess their knowledge of HPV, cervical cancer, and the HPV vaccine, as well as their willingness to pay for the vaccine at the HIV treatment clinic, Nigerian Institute of Medical Research, Lagos. Willingness to pay for the HPV vaccine was also assessed. Multivariable logistic regression models were developed to identify factors associated with willingness to pay for the HPV vaccine. Results: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information. Conclusion: The study found that 79.1% of participants had not heard of the vaccine, and only 29.0% knew of its efficacy in preventing cervical cancer. Moreover, 68.3% of participants were unwilling to pay for the vaccine, and the average amount they were willing to pay was low. Knowledge of HPV, the HPV vaccine, cervical cancer, and income were factors associated with willingness to pay for the vaccine. Health workers were the primary source of information.

Background: Due to the importance of brain death (BD) diagnostic do not mistake, reliable confirmatory exams should be performed to enhance its security. This study aims to evaluate the intracranial pressure (ICP) pulse morphology behavior in brain-dead patients through a noninvasive monitoring system. Methods: A pilot case-control study was conducted in adults that met the BD national protocol criteria. Quantitative data from the ICP waveforms were extracted and analyzed comparing BD patients and health subjects. Results: Fifteen patients were included. ICP waveforms presented substantial differences amidst BD patients when compared to the control group. Moreover, pulse amplitude and time to peak variables values in the case group were also statistically significant. Conclusions: In this exploratory study, noninvasive ICP waveforms have shown potential as a screening method in patients with suspected brain death. Future studies should be carried out in a larger population.

AIM: The study aims to identify if mutations in the SLC4A11 gene are present in Filipino families affected with Congenital Hereditary Endothelial Dystrophy (CHED). METHODS: This is a family cohort study that investigated the genetic profile of a selected family in Northern Luzon, Philippines, whose members were diagnosed with Congenital Hereditary Endothelial Dystrophy (CHED). A patient who was diagnosed with CHED prior to this study, served as the proband for this family. A detailed family history and a complete ophthalmologic examination were done to each of the family members. A total of six affected members and three unaffected members were included in this study. DNA was isolated from peripheral blood samples of family members, and polymerase chain reaction (PCR) was used to amplify the gene’s entire coding region, (19 exons and 2 putative promoter regions), and finally, the amplified regions were analyzed using DNA sequencing. RESULTS: Consanguinity was not present in the family. Corneal haze was reported to be present since birth or shortly thereafter in all affected patients. Slit-lamp examination showed edematous corneas. Molecular studies of the SLC4A11 gene revealed four novel homozygous point mutations variably present in six affected members as well as three unaffected members. One unaffected family member (I-1) had a novel sense mutation absent in other family members. All affected siblings showed little phenotypic variability. CONCLUSION: This is the first report that gives us a genetic profile of a Northern Luzon family with members affected by CHED. This study supports earlier findings that the mutations in the SLC4A11 gene are not consistently the same among different ethnic groups worldwide, probably due to the disease’s genetic heterogeneity. Our study documented five novel mutations adding to the growing list of mutations probably responsible for acquiring the CHED phenotype. It is possible that there are more novel mutations waiting to be discovered in this hereditary disease. Screening for these specific mutations in other families may prove useful for genetic counseling, prenatal diagnosis and the future development of gene therapy.

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevancy of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesions formation in mice fed chow diet, irrespective of sex but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.

Oats are a nutrient rich cereal used for animal feed and growing in human consumption. This cereal can be affected by Fusarium spp., causing the disease Fusarium Head Blight. This disease is caused mainly by species within the Fusarium graminearum species complex, and are also responsible for producing mycotoxins that are harmful to humans and animals. This study aimed to investigate fungal diversity in Brazilian oat samples, focusing on the Fusarium sambucinum species complex and the presence of type B trichothecenes (deoxynivalenol and its derivatives, and nivalenol) from two different regions; Paraná (PR) and Rio Grande do Sul (RS). The isolated fungi from oat grains were identified as species from the genera: Fusarium, Phoma and Alternaria. The majority of Fusarium isolates belonged to the Fusarium sambucinum species complex; identified as F. graminearum s.s., F. meridionale and F. poae. In the RS region, F. poae was the most frequent fungus, while FGSC was the most frequent in the PR region. The majority of F. graminearum s.s. isolates were of the 15-ADON genotype, while some 3-ADON genotypes were identified; however, F. meridionale and F. poae were all of the NIV genotype. Mycotoxin analysis revealed that 92% and 100% of the samples from PR and RS were contaminated with type B trichothecenes, respectively. The oats from PR were predominantly contaminated with DON, whereas NIV was predominant in oats from RS. Analysis showed that 24% of the samples were contaminated with DON at levels higher than Brazilian regulations. Co-contamination of DON, its derivatives and NIV was observed in 84% and 57.7% of the samples from PR and RS, respectively. The results provide new information on Fusarium contamination in Brazilian oats, highlighting the importance for further studies on mycotoxins.

Hadhramout Initiative Against Corona (HIAC ) formed a working group of clinicians relevant to the management of COVID-19 to formulate clinical practice guidelines (CPG) for clinicians caring for the patients infected with COVID-19 in Yemen. The regional guidelines on the management of COVID-19 were thoroughly reviewed and its applicability was assessed for Yemen. HIAC’s recommendations covered (2) sections: the first one is the diagnosis, including case definition, risk stratification of the affected cases, investigations (prioritization of reverse transcription-polymerase chain reaction (RT-PCR) testing, D-dimer, chest x-ray, and chest computed tomography, while the second part covers the treatments (mainly Favipiravir, Remdesivir, Hydroxychloroquine, and Glucocorticoid, Anticoagulants, and Supportive measures). In conclusion, the adoption of cost-effective and evidence-based guidelines in Yemen will standardize the management of the patients infected with COVID-19 and protect both the patients and the health care workers from malpractice.

All infections are potentially curable as long as the etiological agents are susceptible to antimicrobials. The increased rate at which antimicrobials are becoming ineffective is a global health risk of increasing concern that threatens withdrawal of beneficial antimicrobials for disease control. Increased demand for food of animal origin, in particular eggs, meat and milk has led to intensification and commercial production systems where excessive use and misuse of antimicrobials may prevail. Antimicrobials, handled and used by farmers and animal attendants with no formal education may predispose to incorrect dosages, misuse, incorrect applications and non-adherence to withdrawal periods. A multimethod approach (desk review, field study and interviews) was used. Relevant establishments were also visited. High levels of resistance to penicillin G, chloramphenicol, streptomycin and oxytetracycline have been reported especially for Actinobacter pyogenes, Staphylococcus hyicus, Staphylococcus intermedius and Staphylococcus aureus from dairy cattle with mastitis and in humans. Similar trends were found in poultry where eggs and meat are contaminated with Escherichia coli strains resistant to amoxicillin + clavulanate, sulphamethoxazole and neomycin. An increasing trend of emerging multidrug resistant E. coli, Klebsiella pneumoniae, Staphylococcus aureus, and Salmonella was also found in food animals. An in-crease in methicillin resistant Staphlococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) in the livestock sector in Tanzania have been reported. Specific antimicrobials resistant to were ampicillin, augmentin, gentamicin, cotrimoxazole, tetracycline, amoxicillin, ampicillin, gentamicin, streptomycin, erythromycin, tetracycline, ciprofloxacin, nalidixic acid, azithromycin, chloramphenicol, tylosin, erythromycin, cefuroxime, norfloxacin and ciprofloxacin. An in-creased usage of antimicrobials for prophylaxis, anaphylaxis and therapeutics against pathogens and for growth promotion in livestock, aquaculture and crops production were observed. One Health strategic approach is advocated to combat AMR in the food and agriculture sectors in Tanzania. Practical recommendations include a) legislation review and implementation, b) AMU, AMR and AR awareness and advocacy among stakeholders along the value chain, c) strengthening of surveillance and monitoring programs for AMU, AMR and AR, d) enhance development and use of rapid and innovative diagnostic tests and promotion biosecurity principles and e) good husbandry practices. The utilization of this information to improve public health policies and reduce the burden of AMR will be beneficial.

This study tested the association between FecXG point mutation located in exon 2 of BMP15 gene and the prolificacy of Dubasi, Shugor and Watish sheep ecotypes, under dryland farming, Sudan. Blood samples were randomly collected from unrelated 100 ewes (Dubasi; n= 30, Shugor: n= 30, and Watish: n= 40). Bone Morphogenetic protein (BMP15) gene was amplified using PCR-RFLP. Two genotypes were found in all studied breeds (heterozygous and wild type). The calculated total genotype frequencies of BB, Bb and bb genotypes were 0.31, 0.69 and 0.00, respectively, while allele frequencies were 0.66 for B and 0.34 for b. Litter size was influenced by the genotypes of BMP15 gene, parities and subtypes (p<0.05), highest for Watish and 4th parity. Alignment of BMP15 samples along with database reference sequence revealed that most sequence regions were identical except for one variable nucleotide at position 111 bp where a guanine (G) was replaced by adenine (A) in Watish and Shugor samples. All amino acids were the same at residue 275. Watish and Shugor breeds are more related. The study concluded that the presence of one copy of FecXG point mutation of BMP15 gene increased the litter size by 0.17 lambs in the studied ecotypes.

Epithelial-to-mesenchymal transition (EMT) plays a role in chronic obstructive pulmonary diseases (COPD). Cyclic adenosine monophosphate (cAMP) can inhibit transforming growth factor-β1 (TGF-β1) mediated EMT. Although compartmentalization via A-kinase anchoring proteins (AKAPs) is central to cAMP signaling, functional studies on their therapeutic value in the lung EMT process are lacking. Bronchial epithelial (BEAS-2B, primary HAE cells) were exposed to TGF-β1. Epithelial (E-cadherin, ZO-1) and mesenchymal markers collagen Ӏ (mRNA, protein) were analyzed. St-Ht31 disrupted AKAP-PKA interactions. TGF-β1 release was measured by ELISA. TGF-β1-sensitive AKAPs Ezrin, AKAP95 and Yotiao were silenced using siRNA. Cell migration was analyzed by wound healing assay, xCELLigence, Incucyte. Prior to TGF-β1, dibutyryl-cAMP (dbcAMP), fenoterol, rolipram, cilostamide, forskolin were used to elevate intracellular cAMP. TGF-β1 induced morphological changes, decreased E-cadherin but increased collagen Ӏ and cell migration, a process reversed by PF-670462. TGF-β1 altered (mRNA, protein) expression of Ezrin, AKAP95 and Yotiao. St-Ht31 decreased E-cadherin (mRNA, protein), but counteracted TGF-β1-induced collagen Ӏ upregulation. Cigarette smoke (CS) increased TGF-β1 release, activated TGF signaling, augmented cell migration and reduced E-cadherin expression, a process blocked by TGF-β1 neutralizing antibody. Silencing of Ezrin, AKAP95 and Yotiao diminished TGF-β1-induced collagen Ӏ expression, as well as TGF-β1-induced cell migration. Fenoterol, rolipram, and cilostamide, in AKAP silenced cells pointed to distinct cAMP compartments. We conclude that Ezrin, AKAP95 and Yotiao promote TGF-β1-mediated EMT, linked to a TGF-β1 release by CS. AKAP members define the ability of fenoterol, rolipram and cilostamide to modulate the EMT process, and are potential relevant targets in the treatment of COPD.

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

Most Neotropical Psittacidae have a diploid number of 2n=70, and a dichotomy in chromosome patterns. Long-tailed species have biarmed macrochromosomes, while short - tailed ones have telo/acrocentric macrochromosomes. However, the use of chromosome painting with chicken and white hawk probes has demonstrated that karyotype evolution in Psittacidae includes a high number of inter/intrachromosomal rearrangements. Hence, to determine the phylogeny of Long and Short-Tailed species, and to propose a putative ancestral karyotype for this group, we constructed homology maps of Pyrrhura frontalis (PFR) and Amazona aestiva (AAE) and compared them to other previously analyzed long-tailed species. Chromosomes were analyzed by conventional staining and fluorescent in situ hybridization (FISH) using whole chromosome paints of G. gallus (GGA) and L. albicollis (LAL). Conventional staining showed a karyotype with 2n=70 in both species, with biarmed macrochromosomes in Pyrrhura frontalis and telo/acrocentric chromosomes in Amazona aestiva. Comparison of the results with the putative avian ancestral karyotype (PAK) showed fusions in P. frontalis of PAK1p/PAK4q (PFR1) and PAK6/PAK7 (PFR6) with a paracentric inversion in PFR6. However, in A. aestiva there was only the fusion between PAK6/7 (AAE7) with a paracentric inversion. Hybridizations with LAL probes confirmed these results. The results indicate that PFR retained a more basal karyotype than Anodorhynchus hyacinthinus (AHY), Ara macao (AMA) and Ara chloropterus (ACH), because these three species show the fusion PAK8/PAK9 that is not seen in PFR. Hence, we suggest that the ancestral karyotype of species with biarmed chromosomes have the fusions PAK1p/PAK4 and PAK6/PAK7 and, additionally, a pericentric inversion of PAK6/PAK7, while the fusion PAK8/PAK9 would have appeared in the common ancestor of Anodorhynchus hyacinthinus, Ara macao and Ara chloropterus. However, the species A. aestiva shows a characteristic plesiomorphic trait, since PAK1p/PAK4q and PAK8/9 fusions are absent. Our results base on chromosome rearrangements suggest the classification following the criterium of tail length may no reflect the real phylogenetic history of Neotropical Psittacidae.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

The emergence of drug resistance inducing mutations in Hepatitis C virus (HCV) coupled with genotypic heterogeneity has made targeting NS3/4A serine protease difficult. In this work, we investigated the mutagenic variations in the binding pocket of Genotype 3 (G3) HCV NS3/4A and evaluated ligands for efficacious inhibition. We report mutations at 14 positions within the ligand-binding residues of HCV NS3/4A including H57R and S139P within the catalytic triad. We then modeled each mutational variant for pharmacophore-based virtual screening (PBVS) followed by covalent docking towards identifying a potential covalent inhibitor, i.e. cpd-217. The binding stability of cpd-217 was then supported by molecular dynamic simulation followed by MM/GBSA binding free energy calculation. The free energy decomposition analysis indicated that the resistant mutants alter the HCV NS3/4A-ligand interaction, resulting in an unbalanced energy distribution within the binding site leading to drug resistance. cpd-217 was identified to interact with all NS3/4A G3 variants with significant covalent docking scores. In conclusion, cpd-217 emerges as a potential inhibitor of HCV NS3/4A G3 variants that warrants further in vitro and in vivo studies. The study will pave the way for drug design and development of HCV G3 NS3/4A.

Abstract: Effectiveness of a Single Fixed Dose 3 mg Rasburicase for Prevention and Management of Hyperuricemia of Tumor Lysis Syndrome in adult Cancer Patients Background: Tumor lysis syndrome (TLS) is a potentially life-threatening complication associated with certain types of cancer. Rasburicase is an essential medicine required to prevent and treat the hyperuricemia associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed dose strategy of 3 mg rasburicase had been used in many adult cancer patients in our center. Objective: The objective of this study was to assess the effectiveness of a 3 mg fixed dose of rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. Methods: We conducted a retrospective, observational cohort study between March 2020 and November 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum UA levels of

The structure and expression of exogenous genes in transgenic crops are critical for the target traits. R7569 was a mutant event identified in this study with deletion at the 3' end of cry1Ac gene compared to the transgenic insect-resistant cotton MON531 event with commercial application. R7569 has the same exogenous insertion structure as MON531, but with a deletion in the 3' end of the cry1Ac gene and the terminator region. R7569 has a truncated cry1Ac gene with the length of 2,554 bp, encoding 881 amino acids. The transcription termination site was mainly concentrated downstream of the truncated position and extended 160-270 bp from the truncated position using rapid-amplification of cDNA ends (RACE). The transcript levels of cry1Ac genes of R7569 and MON531 decreased gradually at seedling, bud and bell stages, and the transcript levels of cry1Ac genes of R7569 were significantly higher than those of MON531 in seedling and bud stages, but there was no significant difference in the boll stage. The content of Cry1Ac protein in R7569 gradually decreased with the seedling, bud and boll stage, and the content of Cry1Ac protein in all three periods was higher than that of MON531. The insect resistance assay showed that the resistance levels of R7569 and MON531 were both at the high level, and the corrected mortality rate against bollworms was 99.5% and 95.2%, respectively, and there was no significant difference between them. The LC50 value of R7569 was 0.732ng/g dw, with a slope of 1.654 indicating a high level of resistance to bollworm. In this study, for the first time, we found a partial deletion of the target gene in commercially applied transgenic crops, and the partial deletion of the 3' end of the cry1Ac gene retained a better transcription, expression level and insecticidal activity, which can provide a specific case for the safety evaluation of transgenic crops.

Proteases represent common targets in combating infectious diseases including COVID-19. The 3-chymotrypsin-like protease (3CLpro) is a validated molecular target for COVID-19 and it is key for developing potent and selective inhibitors for inhibiting viral replication of SARS-CoV-2. In this review, we discuss structural relationships and diverse subsites of 3CLpro, shedding light on the pivotal role of dimerization and active site architecture in substrate recognition and catalysis. Our analysis of bioinformatics and other published studies unveil a proposal of a novel catalytic mechanism for the SARS-CoV-2 polyprotein cleavage by 3CLpro, centering on the triad mechanism involving His41-Cys145-Asp187 and its indispensable role in viral replication. Recognizing Asp187 as a crucial component in the catalytic process underscores its significance as a fundamental pharmacophoric element in drug design. Next, we provide an overview of both covalent and non-covalent inhibitors, elucidating advancements in drug development observed in preclinical and clinical trials. By highlighting various chemical classes and their pharmacokinetic profiles, our review aims to guide future research directions toward the development of highly selective inhibitors, underscore the significance of 3CLpro as a validated therapeutic target, and propel the progression of drug candidates through preclinical and clinical phases.

Laser in situ keratomileusis (LASIK) is the gold standard in the surgical correction of refractive errors on the cornea. It entails the creation of a superficial hinged corneal flap by a femtosecond laser, ablation of the underlying stromal bed by an excimer laser, and reposition of the flap. The corneal flap can be build in a 2-dimension (2D) fashion with tapered edges, or in a 3-dimension (3D) fashion, with angled sidecut. The latter reduces the risk of flap dislocation and infiltration of epithelial cells. This retrospective study compares with optical coherence tomography 3D and 2D flaps, and respective intra- and early post-operative complications. Four hundred consecutive eyes were included, 200 for each group. In the 3D group, the mean edge angle was 92°. The procedure was in average 5.2 seconds slower in the 3D group (p=0). Non visually significant flap folds were found in 13 eyes of the 2D group and in 7 eyes of the 3D group (p= 0.17). An intracorneal opaque bubble layer induced by laser photodisruption was more commonly observed in the 3D group (9 eyes vs. 2; p=0.03). In conclusion, the creation of a LASIK flap by a 3D-femtosecond laser cut was safe and effective.

Alectinib hydrochloride is an anticancer medication used for the first-line treatment of non-small cell lung cancer. Although it has been approved for medical use ten years ago, and three polymorphs of this substance were proposed based on X-ray diffraction patterns, their crystal structures remained unknown to date. The main problem was preparation of high quality single crystals due to very low solubility of the salt. Herein we report on molecular and crystal structure of form I of alectinib hydrochloride as obtained by powder X-ray diffraction data from laboratory source. The refinement revealed that the nitrogen atom of the morpholinyl ring is protonated. The chloride anion interacts with the H(N) atoms of the morpholine and benzo[b]carbazole rings to form infinite H-bonded chains.

Powdery mildew disease, caused by Sphaerotheca fusca, is a major disease affecting cucumbers cultivated in greenhouses. This study was conducted to find defense genes induced by DL-3-amino-butyric acid (BABA) and powdery mildew in cucumber. The 2000 and 5000 mg/L BABA treated cucumber exhibited disease severity of 25% and 5%, respectively, whereas the water treated cucumber leaves were severely infected, with a disease severity of 90%. BABA did not effect spore germination of the powdery mildew pathogen,. showing BABA is not antifungal agent against the pathogen. In quantitative real-time PCR analysis, BABA treated cucumber upregulated transcriptional level of the defense genes CsPAL, CsPR3,CsPR1, CsLOX1, CsLOX23, Cs LecRK6.1, CsWRKY20, and Cupi4 in cucumber to maximum levels at 48 h, whereas CsLecRK6.1 reached maximum expression after 24 h and futher salicylic acid (SA) levels were significantly increased in BABA-treated cucumber plants. In addition, the infected cucumber with powdery mildew enhanced the expression levels from1.6 to 47.3 fold of the defense genes PAL, PR3, PR1, Lox1, Lox 23, LecRK6.1, WRKY20, and Cupi4 compared to heathy cucumber. The results suggests the BABA induced defense response is associated with SA signal pathway-dependent systemic acquired resistance (SAR) in cucumber, which is involved in plant resistance mechanisms.

Accurate and reliable measurement of real-world walking activity is clinically relevant, particularly for people with mobility difficulties. Insights on walking can help understand mobility function, disease progression, and fall risks. People living in long-term residential care environments have heterogeneous and often pathological walking patterns, making it difficult for conventional algorithms paired with wearable sensors to detect their walking activity. We designed two walking bout detection algorithms for people living in long-term residential care. Both algorithms used thresholds on the magnitude of acceleration from a 3-axis accelerometer on the lower back to classify data as “walking” or “non-walking”. One algorithm had generic thresholds, while the other used personalized thresholds. To validate and evaluate the algorithms, we compared the classifications of walking/non-walking from our algorithms to the real-time research assistant annotated labels and the classification from an algorithm validated on a healthy population. Both the generic and personalized algorithms had acceptable accuracy (0.83 and 0.82 respectively). The personalized algorithm showed the highest specificity (0.84) of all tested algorithms, meaning it was the best suited to determine input data for gait characteristic extraction. The developed algorithms were almost 60% quicker than the previously developed algorithms, suggesting they are adaptable for real-time processing.

Despite being extremely potent against malignancies, cisplatin (CIS) has limited practical applicability due to its adverse effects such as testicular damage. Consequently, it becomes necessary to reduce its toxicity. In this study, cilostazol, a selective phosphodiesterase-3 inhibitor that is frequently used in the treatment of intermittent claudication, was examined for its ability to abrogate CIS-induces testicular toxicity and its ameliorative effect was compared with two phosphodiesterase inhibitors, tadalafil and pentoxifylline. The study also focused on the possible mechanisms involved in the proposed protective effect. Ten groups of rats were included; Group (1): control, Groups (2-4): 5 mg/kg tadalafil or 75 mg/kg pentoxifylline or 20 mg/kg cilostazol respectively), Group (5):7 mg/kg CIS, Group (6&7): CIS + 5 mg/kg tadalafil or 75 mg/kg pentoxifylline, Group (8-10) CIS+ 5, 10 or 20 mg/kg cilostazol respectively. CIS treated rats showed a significant decrease in testicular function, serum testosterone and reduced glutathione levels, and significant elevation in malondialdehyde, total nitrite levels, tumor necrosis factor-alpha and nuclear factor-kappa β alongside caspase-3. These outcomes were confirmed by marked testicular architecture deterioration. Contrary, Cilostazol in a dose-dependent manner showed potential protection against testicular toxicity, reversion of the disrupted testicular function and improvement of the histological alterations through rebalancing of oxidative stress, inflammatory and apoptotic biomarkers. In addition, cilostazol exerted more pronounced protective effect in comparison to tadalafil and pentoxifylline. In conclusion, administrations of cilostazol might ameliorate cisplatin-induced testicular impairment through alteration of oxidative stress, inflammation, and apoptotic pathway, offering a promising treatment for cisplatin -intoxication in the testes.

The objective of this study was to investigate the effects of ethyl nitroacetate, ethyl 2-nitropropionate and 3-nitropropionic acid on ruminal production of CH4, H2, volatile fatty acids (VFAs) and on dry matter digestibility of ground alfalfa under in vitro conditions. In vitro incubations were conducted as consecutive batch cultures. Total gas and amounts of methane produced by ruminal microbes were decreased by all nitrocompounds (P &lt; 0.05). Total production of VFAs was significantly reduced for all the nitrocompounds (P &lt; 0.05) except for NPA. DM disappearance was not affected (P &gt;0.05) by treatment.

Pemphigus vulgaris is an autoimmune blistering disease of the epidermis, caused by autoantibodies against desmosomal proteins, mainly desmogleins 1 and 3, which induce an impairment of desmosomal adhesion and blister formation. Recent findings have shown that inhibition of immunoglobulin G binding on the neonatal Fc receptor, FcRn, results in reduced autoantibody recycling and shortens their half-life, providing a valid treatment option for PV. We have here analyzed the role of FcRn in human keratinocytes treated with novel, recombinant anti-desmoglein-3 antibodies that induce pathogenic changes in desmosomes, such as loss of monolayer integrity, aberrant desmoglein-3 localization and degradation of desmoglein-3. We show that blocking IgG binding on FcRn by efgartigimod, a recombinant Fc fragment that is undergoing clinical studies for pemphigus, stabilizes the keratinocyte monolayer, whereas the loss of desmoglein-3 is not prevented by efgartigimod. Our data show for the first time that FcRn may play a direct role in the pathogenesis of pemphigus at the level of the autoantibody target cells, the epidermal keratinocytes. Our data also imply that in keratinocytes, FcRn may have functions different from its known function in IgG recycling. Therefore, stabilization of keratinocyte adhesion by FcRn blocking entities may provide a novel treatment paradigm for pemphigus.

Toward the standardization of O. biennis sprout extract (OBS-E), we aimed to obtain indicator compounds, using a validated method. HPLC-UVD allowed simultaneous quantification of indicator compounds quercetin 3-glucuronide and ellagic acid. The method was validated in terms of specificity, linearity, precision, accuracy, and limit of detection/limit of quantification (LOD/LOQ). High specificity and linearity was demonstrated, with correlation coefficients of 1.0000 for quercetin 3-glucuronide and 0.9998 for ellagic acid. The LOD/LOQ values were 0.486/1.472 μg/mL for quercetin 3-glucuronide and 1.003/3.039 μg/mL for ellagic acid. Intra-day and inter-day variability tests produced relative standard deviation for each compound of &lt;2%, a generally accepted precision criterion. High recovery rate were also obtained, indicating accuracy validation. The OBS-E prepared using various concentrations of ethanol were then analyzed. The 50% ethanol extract had highest content of quercetin 3-glucuronide, whereas the 70% ethanol extract possessed the lowest. However, the ellagic acid content was highest in the 70% ethanol extract and lowest in the 90% ethanol extract. Thus, quercetin 3-glucuronide and ellagic acid can be used industrially as indicator compounds for O. biennis sprout products, and our validated method can be used to establish indicator compounds for other natural products.

A shrimp oil rich in omega-3 lipids and carotenoids is obtained in remarkably high 5 wt% yield extending to pink shrimp processing waste (head and carapace) the circular economy approach to extract fish oil from fish processing by-products using d-limonene. Biobased limonene, a powerful antimicrobial and antioxidant agent, is an excellent solvent for both lipids and astaxanthin-based carotenoids preventing oxidative degradation during the extraction cycle including solvent and oil separation at 85°C. A new low cost route is established to extract valued marine oil from biowaste annually made available in over 2.2 million tonnes.

Hyperbaric oxygen (HBO) treatment has been proven to attenuate neuroinflammation in rats. This study aimed to determine the potential mechanism underlying the anti-inflammatory effects of HBO treatment on burn-induced neuroinflammation in rats. Thirty-six adult male Sprague–Dawley (SD) rats were randomly assigned to the following six groups (n = 6 per group): (1) sham burn with sham HBO treatment, (2) sham burn with HBO treatment, (3) burn with 1-week sham HBO treatment, (4) burn with 2-week sham HBO treatment, (5) burn with 1-week HBO treatment, and (6) burn with 2-week HBO treatment. SD rats that received third-degree burn injury were used as a full-thickness burn injury model. Subsequently, we analyzed the expression of proteins involved in the galectin-3 (Gal-3)-dependent Toll-like receptor-4 (TLR-4) pathway through enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) analysis, and Western blotting, and a behavior test was also conducted. The behavior test revealed that HBO treatment significantly suppressed mechanical hypersensitivity in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). ELISA results showed that tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) levels in the dorsal horn of the spinal cord and the skin were significantly decreased in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). Western blotting results demonstrated that HBO treatment significantly reduced the expression of Gal-3 and TLR-4 in the dorsal horn of the spinal cord in the burn with HBO treatment group compared with the burn with sham HBO treatment group (p < 0.05). IHC analysis results showed that the expression of Gal-3, TLR-4, CD68, and CD45 in the dorsal horn of the spinal cord was significantly lower in the burn with HBO treatment group than in the burn with sham HBO treatment group (p < 0.05), and the expression of CD68 and macrophage migration inhibitory factor (MIF) in the right hind paw skin was significantly lower. The expression of vimentin and fibroblast growth factor (FGF) in the right hind paw skin was significantly higher after HBO treatment (p < 0.05). This study proved that early HBO treatment relieves neuropathic pain, inhibits the Gal-3-dependent TLR-4 pathway, and suppresses microglia/macrophage activation in a rat model.

A new synthetic approach to polyfunctional hexahydropyrrolo[3,4-b]pyrroles was developed based on cyclization of N-arylbromomaleimides with aminocrotonic acid esters. A highly chemo- and stereoselective reaction is a Hantzsch-type domino process, involving the steps of initial nucleophilic C-addition or substitution and subsequent intramolecular nucleophilic addition without recyclyzation of imide cycle.

Digital solutions in the field of restorative neurology offer significant assistance, enabling patients to engage in rehabilitation activities remotely. This research introduces ReMoVES, an Internet of Medical Things (IoMT) system delivering telemedicine services specifically tailored for Multiple Sclerosis rehabilitation, within the overarching framework of the STORMS project. The ReMoVES platform facilitates the provision of a rehabilitative exercise protocol, seamlessly integrated into the Individual Rehabilitation Project, curated by a multidimensional medical team operating remotely. This manuscript delves into the second phase of the study, elucidating the technology employed, the outcomes achieved, and the practical, professional, and academic implications. The STORMS initiative, as the genesis of digital telerehabilitation solutions, aims to enhance the quality of life for Multiple Sclerosis patients.

Soil organic matter (SOM) is important for the global carbon cycle, and hyperspectral remote sensing has proven a promising method for fast SOM content estimation. However, soil physical properties significantly affect the sensitivity of satellite hyperspectral imaging to SOM, leading to poor generalization ability of the estimation model. This study aims to improve the spatiotemporal transferability of the SOM prediction model by alleviating the coupling effect of soil physical properties on the spectra. Based on satellite hyperspectral images and soil physical variables, including soil moisture (SM), soil surface roughness (root mean squared height, RMSH), and soil bulk weight (SBW), a soil spectral correction strategy was established based on the information unmixing method. Two important grain-producing areas in Northeast China were selected as study areas to verify the performance and transferability of the spectral correction model and SOM content prediction model. The results showed that soil spectral corrections based on fourth-order polynomials and the XG-Boost algorithm had excellent accuracy and generalization ability, with residual predictive deviations (RPD) exceeding 1.4 in almost all bands. In addition, when the soil spectral correction strategy was adopted, the accuracy of the SOM prediction model and the generalization ability after model migration were significantly improved. The SOM prediction accuracy based on the XG-Boost corrected spectrum was the highest, with a coefficient of determination (R2) of 0.76, root mean square error (RMSE) of 5.74 g/kg, and RPD of 1.68. The prediction accuracy, R2, RMSE, and RPD of the model after migration were 0.72, 6.71 g/kg, and 1.53, respectively. Compared with the direct migration prediction of the model, adopting the soil spectral correction strategy based on fourth-order polynomials and XG-Boost reduced the RMSE of the SOM prediction results by 57.90% and 60.27%, respectively. The performance comparison highlighted the advantages of considering soil physical properties in regional-scale SOM prediction.

A sustainable reversed-phase chromatographic method has been developed and validated for the simultaneous determination of three active pharmaceutical ingredients, dorzolamide, brinzolamide, and timolol, used to treat glaucoma. The eco-friendly solvent isopropanol has been used as an organic mobile phase constituent. According to the Hansen space green solvent selection tool, isopropanol has a G score of 6.5, comparable to ethanol, which has a G score of 6.6. The mobile phase consists of isopropanol: aqueous sodium acetate buffer (0.1 M, pH 4.25) in the ratio of 10:90 (v/v). The flow rate was maintained at 1 mL/min. Dorzolamide and brinzolamide were detected at 254 nm, and timolol was detected at 295 nm. A high-purity silica with a polymeric C18 modification column (5 µm,150 x 4.6 mm) was used for this separation. The three compounds were eluted within 8 min. The method was validated according to ICH guidelines. The calibration curves were linear in the range of 20-70 µg/mL, 40-140 µg/mL, and 20-70 µg/mL for dorzolamide, brinzolamide, and timolol, respectively. The LODs were found to be 1.61 µg/mL, 1.60 µg/mL, and 3.16 µg/mL for dorzolamide, brinzolamide, and timolol, respectively. Good accuracy and precision were obtained for the three compounds. The greenness and whiteness of the method were indicated using the AGREE and RGB12 tools, respectively.

Methane and carbon dioxide are the main contributors to global warming, being the methane effect twenty-five times more powerful than carbon dioxide. Although the sources of methane are diverse, it is a very volatile and explosive gas. One way to store the energy content of methane is its conversion to methanol. Methanol is liquid under ambient conditions, easy to transport and, apart from its use as an energy source, it is a chemical platform that can serve as a starting material for the production of various higher value-added products. Accordingly, the transformation of methane to methanol has been extensively treated in the literature, using traditional catalysts as different types of zeolites. However, in the last years, a new generation of catalysts have emerged to carry out this transformation with higher conversion and selectivity, and more importantly, under mild temperature and pressure conditions. These new catalysts typically involve the use of a highly porous supporting material such as zeolite, or more recently, metal-organic frameworks (MOFs) and graphene, and metallic nanoparticles or a combination of different types of nanoparticles that are the core of the catalytic process. In this review, the characteristics, the catalytic mechanisms, reactors, and the main results of these catalysts are presented as a way to overcome the challenges found in traditional catalysts.

This study examines the Willingness-To-Pay (WTP) of consumers and the determinants of eco-labeling for the organic cocoa powder produced in the Dong Nai UNESCO Biosphere Reserve (DNBR), Southern Vietnam. Eco-labels are designed according to Tiers of eco-labeling for biosphere reserves (BR) introduced by UNESCO include BR Destination (Tier 1), BR Quality Label (Tier 2), and Professional Certification Label (Tier 3). Questionnaires are delivered to 203 customers in the DNBR and nearby places, such as Dong Nai and HCMC. This study employs a hybrid approach using descriptive statistics, ANOVA test, and Partial Least Squares Structural Equation Model (PLS-SEM). The results indicate that gender and educational level have a positive effect on consumers' preferences. Customers are willing to pay more for cocoa powder with an eco-label than one with an organic label. Perceived food safety and product knowledge lower customers’ WTP, whereas agricultural environment and pricing concerns increase it. Tier 2 is suggested for labeling cocoa powder in the DNBR. The DNBR Management Board, together with the federal and provincial governments, should all follow a similar certification process. Increased eco-label awareness is crucial for the future of environmentally responsible shopping and responsible business practices.

Meat-based diets are still the norm and vegans and vegetarians represent only a small minority of the population. A transition respectively behavioural change towards a diet with less meat can only occur with the adoption of a positive attitude towards dietary changes based on reasons and motivations. The main aim of this study is to validate the so-called meat attachment scale (MEAS) for Germany in order to analyse if this construct is a barrier towards a diet with less meat in this country. The findings show that the MEAS can be applied in Germany and a similar structure as reported for Spain and other countries could be found. Furthermore, a correlation analysis demonstrated that food neophobia and MEAS are not correlated with each other. That is, that meat attachment represents an independent and single predictor for trust in food (processing) technologies as e.g. plant-based proteins or cultured meat.