Demethylation and Up-Regulation of an Oncogene after Hypomethylating Therapy.

BACKGROUND: Although hypomethylating agents are currently used to treat patients with cancer, whether they can also reactivate and up-regulate oncogenes is not well elucidated. METHODS: We examined the effect of hypomethylating agents on SALL4, a known oncogene that plays an important role in myelodysplastic syndrome and other cancers. Paired bone marrow samples that were obtained from two cohorts of patients with myelodysplastic syndrome before and after treatment with a hypomethylating agent were used to explore the relationships among changes in SALL4 expression, treatment response, and clinical outcome. Leukemic cell lines with low or undetectable SALL4 expression were used to study the relationship between SALL4 methylation and expression. A locus-specific demethylation technology, CRISPR-DNMT1-interacting RNA (CRISPR-DiR), was used to identify the CpG island that is critical for SALL4 expression. RESULTS: SALL4 up-regulation after treatment with hypomethylating agents was observed in 10 of 25 patients (40%) in cohort 1 and in 13 of 43 patients (30%) in cohort 2 and was associated with a worse outcome. Using CRISPR-DiR, we discovered that demethylation of a CpG island within the 5' untranslated region was critical for SALL4 expression. In cell lines and patients, we confirmed that treatment with a hypomethylating agent led to demethylation of the same CpG region and up-regulation of SALL4 expression. CONCLUSIONS: By combining analysis of patient samples with CRISPR-DiR technology, we found that demethylation and up-regulation of an oncogene after treatment with a hypomethylating agent can indeed occur and should be further studied. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).

Broad-spectrum resistance gene RPW8.1 balances immunity and growth via feedback regulation of WRKYs.

Arabidopsis RESISTANCE TO POWDERY MILDEW 8.1 (RPW8.1) is an important tool for engineering broad-spectrum disease resistance against multiple pathogens. Ectopic expression of RPW8.1 leads to enhanced disease resistance with cell death at leaves and compromised plant growth, implying a regulatory mechanism balancing RPW8.1-mediated resistance and growth. Here, we show that RPW8.1 constitutively enhances the expression of transcription factor WRKY51 and activates salicylic acid and ethylene signalling pathways; WRKY51 in turn suppresses RPW8.1 expression, forming a feedback regulation loop. RPW8.1 and WRKY51 are both induced by pathogen infection and pathogen-/microbe-associated molecular patterns. In ectopic expression of RPW8.1 background (R1Y4), overexpression of WRKY51 not only rescues the growth suppression and cell death caused by RPW8.1, but also suppresses RPW8.1-mediated broad-spectrum disease resistance and pattern-triggered immunity. Mechanistically, WRKY51 directly binds to and represses RPW8.1 promoter, thus limiting the expression amplitude of RPW8.1. Moreover, WRKY6, WRKY28 and WRKY41 play a role redundant to WRKY51 in the suppression of RPW8.1 expression and are constitutively upregulated in R1Y4 plants with WRKY51 being knocked out (wrky51 R1Y4) plants. Notably, WRKY51 has no significant effects on disease resistance or plant growth in wild type without RPW8.1, indicating a specific role in RPW8.1-mediated disease resistance. Altogether, our results reveal a regulatory circuit controlling the accumulation of RPW8.1 to an appropriate level to precisely balance growth and disease resistance during pathogen invasion.

Divergence of active site motifs among different classes of Populus glutaredoxins results in substrate switches.

Enzymes are essential components of all biological systems. The key characteristics of proteins functioning as enzymes are their substrate specificities and catalytic efficiencies. In plants, most genes encoding enzymes are members of large gene families. Within such families, the contributions of active site motifs to the functional divergence of duplicate genes have not been well elucidated. In this study, we identified 41 glutaredoxin (GRX) genes in the Populus trichocarpa genome. GRXs are ubiquitous enzymes in plants that play important roles in developmental and stress tolerance processes. In poplar, GRX genes were divided into four classes based on clear differences in gene structure and expression pattern, subcellular localization, enzymatic activity, and substrate specificity of the encoded proteins. Using site-directed mutagenesis, this study revealed that the divergence of the active site motif among different classes of GRX proteins resulted in substrate switches and thus provided new insights into the molecular evolution of these important plant enzymes.

Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China.

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.

Research on synthesis and property of nano-textured Sc2O3-MgO efficient antibacterial agents.

In order to obtain the inorganic efficient antibacterial agents, the means of ion doping and morphology construction in this research are used to enhance the antibacterial property of nano-MgO, which is according to the "oxidative damage mechanism" and "contact mechanism". In this work, the nano-textured Sc2O3-MgO are synthesized by doping Sc3+ in nano-MgO lattice through calcining at 600 °C. When the Sc3+ content reaches 10%, the nanotextures on the powders surface are pretty clearly visible and uniform, and the specific surface area and the oxygen vacancy are ideal, so that the 10% Sc3+-doped powders (SM-10) has the excellent antibacterial property against E. coli and S. aureus (MBC = 0.03 mg/mL). The efficient antibacterial agents in this research have a better antibacterial effect than the 0% Sc3+-doped powders (SM-0, MBC = 0.20 mg/mL) and the commercial nano-MgO (CM, MBC = 0.40 mg/mL), which have application prospects in the field of antibacterial.

Preparation and Properties of (Sc2O3-MgO)/Pcl/Pvp Electrospun Nanofiber Membranes for the Inhibition of Escherichia coli Infections.

Due to their high porosity, large specific surface area, and structural similarity with the extracellular matrix (ECM), electrospun nanofiber membranes are often endowed with the antibacterial properties for biomedical applications. The purpose of this study was to synthesize nano-structured Sc2O3-MgO by doping Sc3+, calcining at 600 °C, and then loading it onto the PCL/PVP substrates with electrospinning technology with the aim of developing new efficient antibacterial nanofiber membranes for tissue engineering. A scanning electron microscope (SEM) and energy dispersive X-ray spectrometer (EDS) were used to study the morphology of all formulations and analyze the types and contents of the elements, and an X-ray diffraction (XRD), thermogravimetric analysis (TGA), and Fourier transform attenuated total reflection infrared spectroscopy (ATR-FTIR) were used for further analysis. The experimental results showed that the PCL/PVP (SMCV-2.0) nanofibers loaded with 2.0 wt% Sc2O3-MgO were smooth and homogeneous with an average diameter of 252.6 nm; the antibacterial test indicated that a low load concentration of 2.0 wt% Sc2O3-MgO in PCL/PVP (SMCV-2.0) showed a 100% antibacterial rate against Escherichia coli (E. coli).

The Larix kaempferi genome reveals new insights into wood properties.

Here, through single-molecule real-time sequencing, we present a high-quality genome sequence of the Japanese larch (Larix kaempferi), a conifer species with great value for wood production and ecological afforestation. The assembled genome is 10.97 Gb in size, harboring 45,828 protein-coding genes. Of the genome, 66.8% consists of repeat sequences, of which long terminal repeat retrotransposons are dominant and make up 69.86%. We find that tandem duplications have been responsible for the expansion of genes involved in transcriptional regulation and stress responses, unveiling their crucial roles in adaptive evolution. Population transcriptome analysis reveals that lignin content in L. kaempferi is mainly determined by the process of monolignol polymerization. The expression values of six genes (LkCOMT7, LkCOMT8, LkLAC23, LkLAC102, LkPRX148, and LkPRX166) have significantly positive correlations with lignin content. These results indicated that the increased expression of these six genes might be responsible for the high lignin content of the larches' wood. Overall, this study provides new genome resources for investigating the evolution and biological function of conifer trees, and also offers new insights into wood properties of larches.

Frequent ploidy changes in Salicaceae indicates widespread sharing of the salicoid whole genome duplication by the relatives of Populus L. and Salix L.

BACKGROUNDS: Populus and Salix belong to Salicaceae and are used as models to investigate woody plant physiology. The variation of karyotype and nuclear DNA content can partly reflect the evolutionary history of the whole genome, and can provide critical information for understanding, predicting, and potentially ameliorating the woody plant traits. Therefore, it is essential to study the chromosome number (CN) and genome size in detail to provide information for revealing the evolutionary process of Salicaceae. RESULTS: In this study, we report the somatic CNs of seventeen species from eight genera in Salicaceae. Of these, CNs for twelve species and for five genera are reported for the first time. Among the three subfamilies of Salicaceae, the available data indicate CN in Samydoideae is n = 21, 22, 42. The only two genera, Dianyuea and Scyphostegia, in Scyphostegioideae respectively have n = 9 and 18. In Salicoideae, Populus, Salix and five genera closely related to them (Bennettiodendron, Idesia, Carrierea, Poliothyrsis, Itoa) are based on relatively high CNs from n = 19, 20, 21, 22 to n = 95 in Salix. However, the other genera of Salicoideae are mainly based on relatively low CNs of n = 9, 10, 11. The genome sizes of 35 taxa belonging to 14 genera of Salicaceae were estimated. Of these, the genome sizes of 12 genera and all taxa except Populus euphratica are first reported. Except for Dianyuea, Idesia and Bennettiodendron, all examined species have relatively small genome sizes of less than 1 pg, although polyploidization exists. CONCLUSIONS: The variation of CN and genome size across Salicaceae indicates frequent ploidy changes and a widespread sharing of the salicoid whole genome duplication (WGD) by the relatives of Populus and Salix. The shrinkage of genome size after WGD indicates massive loss of genomic components. The phylogenetic asymmetry in clade of Populus, Salix, and their close relatives suggests that there is a lag-time for the subsequent radiations after the salicoid WGD event. Our results provide useful data for studying the evolutionary events of Salicaceae.

A High-Temperature Na-Ion Battery: Boosting the Rate Capability and Cycle Life by Structure Engineering.

High-temperature sodium ion batteries (SIBs) have drawn significant heed recently for large-scale energy storage. Yet, conventional SIBs are in the depths of inferior charge/discharge efficiency and cyclability at elevated temperatures. Rational structure design is highly desirable. Hence, a 3D hierarchical flower architecture self-assembled by carbon-coated Na3 V2 (PO4 )3 (NVP) nanosheets (NVP@C-NS-FL) is fabricated via a microwave-assisted glycerol-mediated hydrothermal reaction combined with a post heat-treatment. The growth mechanism of NVP@C-NS-FL is systematically investigated, by forming a microspherical glycerol/polyglycerol-NVP complex initially and then converting into flower-like architecture during the subsequent annealing at a low temperature ramping rate. Benefiting from the integrated structure, fast Na+ transportation, and highly effective heat transfer, the as-obtained NVP@C-NS-FL exhibits an excellent high-temperature SIB performance, e.g., 65 mAh g-1 (100 C) after 1000 cycles under 60 °C. When coupled with NaTi2 (PO4 )3 anode, the full cell can still display superior power capability of 1.4 kW kg-1 and long-term cyclability (2000 cycles) under 60 °C.

Functional and structural profiles of GST gene family from three Populus species reveal the sequence-function decoupling of orthologous genes.

A common assumption in comparative genomics is that orthologous genes are functionally more similar than paralogous genes. However, the validity of this assumption needs to be assessed using robust experimental data. We conducted tissue-specific gene expression and protein function analyses of orthologous groups within the glutathione S-transferase (GST) gene family in three closely related Populus species: Populus trichocarpa, Populus euphratica and Populus yatungensis. This study identified 21 GST orthologous groups in the three Populus species. Although the sequences of the GST orthologous groups were highly conserved, the divergence in enzymatic functions was prevalent. Through site-directed mutagenesis of orthologous proteins, this study revealed that nonsynonymous substitutions at key amino acid sites played an important role in the divergence of enzymatic functions. In particular, a single amino acid mutation (Arg39→Trp39) contributed to P. euphratica PeGSTU30 possessing high enzymatic activity via increasing the hydrophobicity of the active cavity. This study provided experimental evidence showing that orthologues belonging to the gene family have functional divergences. The nonsynonymous substitutions at a few amino acid sites resulted in functional divergence of the orthologous genes. Our findings provide new insights into the evolution of orthologous genes in closely related species.

Evolution and Function of the Populus SABATH Family Reveal That a Single Amino Acid Change Results in a Substrate Switch.

Evolutionary mechanisms of substrate specificities of enzyme families remain poorly understood. Plant SABATH methyltransferases catalyze methylation of the carboxyl group of various low molecular weight metabolites. Investigation of the functional diversification of the SABATH family in plants could shed light on the evolution of substrate specificities in this enzyme family. Previous studies identified 28 SABATH genes from the Populus trichocarpa genome. In this study, we re-annotated the Populus SABATH gene family, and performed molecular evolution, gene expression and biochemical analyses of this large gene family. Twenty-eight Populus SABATH genes were divided into three classes with distinct divergences in their gene structure, expression responses to abiotic stressors and enzymatic properties of encoded proteins. Populus class I SABATH proteins converted IAA to methyl-IAA, class II SABATH proteins converted benzoic acid (BA) and salicylic acid (SA) to methyl-BA and methyl-SA, while class III SABATH proteins converted farnesoic acid (FA) to methyl-FA. For Populus class II SABATH proteins, both forward and reverse mutagenesis studies showed that a single amino acid switch between PtSABATH4 and PtSABATH24 resulted in substrate switch. Our findings provide new insights into the evolution of substrate specificities of enzyme families.

Structural insight into the type-II mitochondrial NADH dehydrogenases.

The single-component type-II NADH dehydrogenases (NDH-2s) serve as alternatives to the multisubunit respiratory complex I (type-I NADH dehydrogenase (NDH-1), also called NADH:ubiquinone oxidoreductase; EC 1.6.5.3) in catalysing electron transfer from NADH to ubiquinone in the mitochondrial respiratory chain. The yeast NDH-2 (Ndi1) oxidizes NADH on the matrix side and reduces ubiquinone to maintain mitochondrial NADH/NAD(+) homeostasis. Ndi1 is a potential therapeutic agent for human diseases caused by complex I defects, particularly Parkinson's disease, because its expression restores the mitochondrial activity in animals with complex I deficiency. NDH-2s in pathogenic microorganisms are viable targets for new antibiotics. Here we solve the crystal structures of Ndi1 in its substrate-free, NADH-, ubiquinone- and NADH-ubiquinone-bound states, to help understand the catalytic mechanism of NDH-2s. We find that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting. The structures reveal two ubiquinone-binding sites (UQ(I) and UQ(II)) in Ndi1. NADH and UQ(I) can bind to Ndi1 simultaneously to form a substrate-protein complex. We propose that UQ(I) interacts with FAD to act as an intermediate for electron transfer, and that NADH transfers electrons through this FAD-UQ(I) complex to UQ(II). Together our data reveal the regulatory and catalytic mechanisms of Ndi1 and may facilitate the development or targeting of NDH-2s for potential therapeutic applications.

Study on the effects of organic matter characteristics on the residual aluminum and flocs in coagulation processes.

Characteristics of organic matter may affect the residual aluminum after the coagulation process. This study reported the results of a survey for one drinking water treatment plant and measured the concentration of residual aluminum species with different molecular weights. Survey results indicated that humic acid or organic matter whose molecular weight was smaller than 1500Da had significant effects on residual aluminum. All the treatment processes were ineffective in removing dissolved organic matter whose molecular weight was smaller than 1500Da. These results also indicated that the addition of sand or polyacrylamide in the coagulation process could greatly decrease the concentration of humic acid, and the concentration of residual aluminum also decreased. These results revealed that for all water samples after filtration, the majority of total residual aluminum existed in the form of total dissolved aluminum, accounting for 70%-90%. The concentration of residual aluminum produced in bovine serum albumin solutions indicated that when the DOC was larger than 4.0mg/L, there were still significant differences when the solution pH value varied from 4.0 to 9.0.

Loss of α-Tubulin Acetylation Is Associated with TGF-ß-induced Epithelial-Mesenchymal Transition.

The epithelial-to-mesenchymal transition (EMT) is a process by which differentiated epithelial cells reprogram gene expression, lose their junctions and polarity, reorganize their cytoskeleton, increase cell motility and assume a mesenchymal morphology. Despite the critical functions of the microtubule (MT) in cytoskeletal organization, how it participates in EMT induction and maintenance remains poorly understood. Here we report that acetylated α-tubulin, which plays an important role in microtubule (MT) stabilization and cell morphology, can serve as a novel regulator and marker of EMT. A high level of acetylated α-tubulin was correlated with epithelial morphology and it profoundly decreased during TGF-ß-induced EMT. We found that TGF-ß increased the activity of HDAC6, a major deacetylase of α-tubulin, without affecting its expression levels. Treatment with HDAC6 inhibitor tubacin or TGF-ß type I receptor inhibitor SB431542 restored the level of acetylated α-tubulin and consequently blocked EMT. Our results demonstrate that acetylated α-tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process.

Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family.

Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families.

Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.

Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.

Functional divergence of the glutathione S-transferase supergene family in Physcomitrella patens reveals complex patterns of large gene family evolution in land plants.

Plant glutathione S-transferases (GSTs) are multifunctional proteins encoded by a large gene family that play major roles in the detoxification of xenobiotics and oxidative stress metabolism. To date, studies on the GST gene family have focused mainly on vascular plants (particularly agricultural plants). In contrast, little information is available on the molecular characteristics of this large gene family in nonvascular plants. In addition, the evolutionary patterns of this family in land plants remain unclear. In this study, we identified 37 GST genes from the whole genome of the moss Physcomitrella patens, a nonvascular representative of early land plants. The 37 P. patens GSTs were divided into 10 classes, including two new classes (hemerythrin and iota). However, no tau GSTs were identified, which represent the largest class among vascular plants. P. patens GST gene family members showed extensive functional divergence in their gene structures, gene expression responses to abiotic stressors, enzymatic characteristics, and the subcellular locations of the encoded proteins. A joint phylogenetic analysis of GSTs from P. patens and other higher vascular plants showed that different class GSTs had distinct duplication patterns during the evolution of land plants. By examining multiple characteristics, this study revealed complex patterns of evolutionary divergence among the GST gene family in land plants.

Enhancing sustainability in medical product supply chains: The role of remanufacturing and government subsidies.

This study explores the impact of government subsidies on the production dynamics within the medical product supply chain, particularly focusing on the remanufacturing of medical goods. Amidst the backdrop of the COVID-19 pandemic, which has underscored the critical shortages in medical supplies, our research delves into the adoption of remanufacturing practices by medical product manufacturers as a strategic response to these shortages and environmental concerns. We investigate how government subsidies influence the production volumes of original manufacturers and remanufacturers and examine the competitive interplay between newly manufactured and remanufactured medical products. Through the development of three production game models-Scenario B (manufacturers produce both new and refurbished products), Scenario N (separate production of new and refurbished products by manufacturers and remanufacturers, respectively), and Scenario C (similar to Scenario N but includes a certification fee paid by remanufacturers to original manufacturers)-we analyze the strategies that could mitigate supply deficiencies during medical crises. Our findings indicate that the certification strategy (Scenario C) not only yields the highest total production of medical products but also offers a viable solution to enhance the sustainability of the entire medical production system by alleviating supply chain disruptions. Furthermore, we discuss the managerial implications of our results, emphasizing the potential of a joint remanufacturing strategy to stabilize the supply chain and foster environmental conservation. Lastly, we highlight our study's limitations and suggest future research directions, particularly concerning the variability in product quality and the reliance on government subsidies. This research contributes to a nuanced understanding of green remanufacturing within the pharmaceutical supply chain, offering insights for manufacturers, remanufacturers, and policymakers aiming for sustainable industry practices.

Association of HTR1A Gene Polymorphisms with Efficacy and Plasma Concentrations of Atypical Antipsychotics in the Treatment of Male Patients with Schizophrenia.

Purpose: We investigate the association of HTR1A rs10042486 and rs6295 with efficacy and plasma concentrations of atypical antipsychotics in the treatment of male patients with schizophrenia. Patients and Methods: A total of 140 male patients diagnosed with schizophrenia who were treated with any single atypical antipsychotic between May 2020 and May 2022 were retrospectively included. Clinical symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). All SNPs were typed using Agena Bioscience MassARRAY DNA mass spectrometry. Plasma concentrations of antipsychotics at week 3, 6 and 12 after treatment commence were analyzed using mass spectrometry. Results: For efficacy of atypical antipsychotics, we observed no significant difference between HTR1A rs10042486, rs6295 and positive symptom improvement, where the patients with heterozygous mutant at the rs10042486 and rs6295 locus were superior to those with wild-type or homozygous mutant genotypes on negative symptom improvement, especially at 12 weeks of follow-up when the difference between genotypes at the rs6295 locus have statistical significance (P = 0.037). For plasma concentration, we found that quetiapine plasma concentrations were significantly lower in patients with mutation-heterozygous types than in wild-type and homozygous mutation genotypes at week 6. In contrast, higher plasma concentrations were found for mutant heterozygous than wild genotypes in the risperidone monotherapy analysis, and the difference among genotypes at the rs6295 locus was statistically significant at 6 weeks of follow-up. Conclusion: The assessment of the correlation of genetic polymorphisms of HTR1A rs6295 and rs10042486 in male patients with schizophrenia with the monitoring of therapeutic drug concentrations and therapeutic efficacy provides a constructive foundation for the clinical individualization of antipsychotics, such as quetiapine and risperidone, which is important in selecting the dose of the medication and improving the improvement of negative symptoms.

Design and characterization of edible chitooligosaccharide/fish skin gelatin nanofiber-based hydrogel with antibacterial and antioxidant characteristics.

Antibacterial and active packaging materials have gained significant research attention in response to the growing interest in food packaging. In this investigation, we developed hydrogel packaging materials with antibacterial and antioxidant properties by incorporating chitooligosaccharide (COS) and fish skin gelatin (FSG) nanofiber membranes, which readily absorbed water and exhibited swelling characteristics. The nanofiber membranes were fabricated by electrospinning technology, embedding COS within FSG, and subsequently crosslinked through the Maillard reaction facilitated by the addition of glucose. The behavior of conductivity, viscosity, and surface tension in the spinning solutions was analyzed to understand their variation patterns. Scanning electron microscopy (SEM) results revealed that the crosslinked COS/FSG nanofiber membranes possessed a uniform yet disordered fiber structure, with the diameter of the nanofibers increasing as the COS content increased. Remarkably, when the COS content reached 25 %, the COS/FSG nanofiber membranes (CF-C-25) exhibited a suitable fiber diameter of 437.16 ± 63.20 nm. Furthermore, the thermal crosslinking process involving glucose supplementation enhanced the hydrophobicity of CF-C-25. Upon hydration, the CF-H-25 hydrogel displayed a distinctive porous structure, exhibiting a remarkable swelling rate of 954 %. Notably, the inclusion of COS significantly augmented the antibacterial and antioxidant properties of the hydrogel-based nanofiber membranes. CF-H-25 demonstrated an impressive growth inhibition of 90.56 ± 5.91 % against E. coli, coupled with excellent antioxidant capabilities. In continuation, we performed a comprehensive analysis of the total colony count, pH, TVB-N, and TBA of crucian carp. The CF-H-25 hydrogel proved highly effective in extending the shelf life of crucian carp by 2-4 days, suggesting its potential application as an edible membrane for aquatic product packaging.