Identification of QTLs and candidate genes for water-soluble protein content in soybean seeds.

Soybean represents a vital source of premium plant-based proteins for human nutrition. Importantly, the level of water-soluble protein (WSP) is crucial for determining the overall quality and nutritional value of such crops. Enhancing WSP levels in soybean plants is a high-priority goal in crop improvement. This study aimed to elucidate the genetic basis of WSP content in soybean seeds by identifying quantitative trait loci (QTLs) and set the foundation for subsequent gene cloning and functional analysis. Using 180 F10 recombinant inbred lines generated by crossing the high-protein soybean cultivar JiDou 12 with the wild variety Ye 9, our researcher team mapped the QTLs influencing protein levels, integrating Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene expression profiling to identify candidate genes. During the 2020 and 2022 growing seasons, a standard bell-shaped distribution of protein content trait data was observed in these soybean lines. Eight QTLs affecting protein content were found across eight chromosomes, with LOD scores ranging from 2.59 to 7.30, explaining 4.15-11.74% of the phenotypic variance. Notably, two QTLs were newly discovered, one with a elite allele at qWSPC-15 from Ye 9. The major QTL, qWSPC-19, on chromosome 19 was stable across conditions and contained genes involved in nitrogen metabolism, amino acid biosynthesis, and signaling. Two genes from this QTL, Glyma.19G185700 and Glyma.19G186000, exhibited distinct expression patterns at maturity, highlighting the influence of these genes on protein content. This research revealed eight QTLs for WSP content in soybean seeds and proposed a gene for the key QTL qWSPC-19, laying groundwork for gene isolation and enhanced soybean breeding through the use of molecular markers. These insights are instrumental for developing protein-rich soybean cultivars.

Characterization and mitigation of artifacts derived from NGS library preparation due to structure-specific sequences in the human genome.

BACKGROUND: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. RESULTS: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses. CONCLUSIONS: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

A comprehensive analysis of the WRKY family in soybean and functional analysis of GmWRKY164-GmGSL7c in resistance to soybean mosaic virus.

BACKGROUND: Soybean mosaic disease caused by soybean mosaic virus (SMV) is one of the most devastating and widespread diseases in soybean producing areas worldwide. The WRKY transcription factors (TFs) are widely involved in plant development and stress responses. However, the roles of the GmWRKY TFs in resistance to SMV are largely unclear. RESULTS: Here, 185 GmWRKYs were characterized in soybean (Glycine max), among which 60 GmWRKY genes were differentially expressed during SMV infection according to the transcriptome data. The transcriptome data and RT-qPCR results showed that the expression of GmWRKY164 decreased after imidazole treatment and had higher expression levels in the incompatible combination between soybean cultivar variety Jidou 7 and SMV strain N3. Remarkably, the silencing of GmWRKY164 reduced callose deposition and enhanced virus spread during SMV infection. In addition, the transcript levels of the GmGSL7c were dramatically lower upon the silencing of GmWRKY164. Furthermore, EMSA and ChIP-qPCR revealed that GmWRKY164 can directly bind to the promoter of GmGSL7c, which contains the W-box element. CONCLUSION: Our findings suggest that GmWRKY164 plays a positive role in resistance to SMV infection by regulating the expression of GmGSL7c, resulting in the deposition of callose and the inhibition of viral movement, which provides guidance for future studies in understanding virus-resistance mechanisms in soybean.

Cold tolerance SNPs and candidate gene mining in the soybean germination stage based on genome-wide association analysis.

KEY MESSAGE: Three QTLs associated with low-temperature tolerance were identified by genome-wide association analysis, and 15 candidate genes were identified by haplotype analysis and gene expression analyses. Low temperature is a critical factor affecting the geographical distribution, growth, development, and yield of soybeans, with cold stress during seed germination leading to substantial productivity loss. In this study, an association panel comprising 260 soybean accessions was evaluated for four germination traits and four cold tolerance index traits, revealing extensive variation in cold tolerance. Genome-wide association study (GWAS) identified 10 quantitative trait nucleotides (QTNs) associated with cold tolerance, utilizing 30,799 single nucleotide polymorphisms (SNPs) and four GWAS models. Linkage disequilibrium (LD) analysis positioned these QTNs within three cold-tolerance quantitative trait loci (QTL) and, with QTL19-1, was positioned by three multi-locus models, underscoring its importance as a key QTL. Integrative haplotype analysis, supplemented by transcriptome analysis, uncovered 15 candidate genes. The haplotypes within the genes Glyma.18G044200, Glyma.18G044300, Glyma.18G044900, Glyma.18G045100, Glyma.19G222500, and Glyma.19G222600 exhibited significant phenotypic variations, with differential expression in materials with varying cold tolerance. The QTNs and candidate genes identified in this study offer substantial potential for marker-assisted selection and gene editing in breeding cold-tolerant soybeans, providing valuable insights into the genetic mechanisms underlying cold tolerance during soybean germination.

Genome dosage alteration caused by chromosome pyramiding and shuffling effects on karyotypic heterogeneity, reproductive diversity, and phenotypic variation in Zea-Tripsacum allopolyploids.

KEY MESSAGE: We developed an array of Zea-Tripsacum tri-hybrid allopolyploids with multiple ploidies. We unveiled that changes in genome dosage due to the chromosomes pyramiding and shuffling of three species effects karyotypic heterogeneity, reproductive diversity, and phenotypic variation in Zea-Tripsacum allopolyploids. Polyploidy, or whole genome duplication, has played a major role in evolution and speciation. The genomic consequences of polyploidy have been extensively studied in many plants; however, the extent of chromosomal variation, genome dosage, phenotypic diversity, and heterosis in allopolyploids derived from multiple species remains largely unknown. To address this question, we synthesized an allohexaploid involving Zea mays, Tripsacum dactyloides, and Z. perennis by chromosomal pyramiding. Subsequently, an allooctoploid and an allopentaploid were obtained by hybridization of the allohexaploid with Z. perennis. Moreover, we constructed three populations with different ploidy by chromosomal shuffling (allopentaploid × Z. perennis, allohexaploid × Z. perennis, and allooctoploid × Z. perennis). We have observed 3 types of sexual reproductive modes and 2 types of asexual reproduction modes in the tri-species hybrids, including 2n gamete fusion (2n + n), haploid gamete fusion (n + n), polyspermy fertilization (n + n + n) or 2n gamete fusion (n + 2n), haploid gametophyte apomixis, and asexual reproduction. The tri-hybrids library presents extremely rich karyotype heterogeneity. Chromosomal compensation appears to exist between maize and Z. perennis. A rise in the ploidy of the trihybrids was linked to a higher frequency of chromosomal translocation. Variation in the degree of phenotypic diversity observed in different segregating populations suggested that genome dosage effects phenotypic manifestation. These findings not only broaden our understanding of the mechanisms of polyploid formation and reproductive diversity but also provide a novel insight into genome pyramiding and shuffling driven genome dosage effects and phenotypic diversity.

A preliminary prediction model of pediatric Mycoplasma pneumoniae pneumonia based on routine blood parameters by using machine learning method.

BACKGROUND: The prevalence and severity of pediatric Mycoplasma pneumoniae pneumonia (MPP) poses a significant threat to the health and lives of children. In this study, we aim to systematically evaluate the value of routine blood parameters in predicting MPP and develop a robust and generalizable ensemble artificial intelligence (AI) model to assist in identifying patients with MPP. METHODS: We collected 27 features, including routine blood parameters and hs-CRP levels, from patients admitted to The Affiliated Dazu's Hospital of Chongqing Medical University with or without MPP between January, 2023 and January, 2024. A classification model was built using seven machine learning (ML) algorithms to develop an integrated prediction tool for diagnosing MPP. It was evaluated on both an internal validation set (982 individuals) and an external validation set (195 individuals). The primary outcome measured the accuracy of the model in predicting MPP. RESULTS: The GBDT is state-of-the-art based on 27 features. Following inter-laboratory cohort testing, the GBDT demonstrated an AUC, accuracy, specificity, sensitivity, PPV, NPV, and F1-score of 0.980 (0.938-0.995), 0.928 (0.796-0.970), 0.929 (0.717-1.000), 0.926 (0.889-0.956), 0.922 (0.727-1.000), 0.937 (0.884-0.963), and 0.923 (0.800-0.966) in stratified 10-fold cross-validation. A GBDT-based AI Lab was developed to facilitate the healthcare providers in remote and impoverished areas. CONCLUSIONS: The GBDT-based AI Lab tool, with high sensitivity and specificity, could help discriminate between pediatric MPP infection and non-MPP infection based on routine blood parameters. Moreover, a user-friendly webpage tool for AI Lab could facilitate healthcare providers in remote and impoverished areas where advanced technologies are not accessible.

Dissecting the role of soybean rhizosphere-enriched bacterial taxa in modulating nitrogen-cycling functions.

Crop roots selectively recruit certain microbial taxa that are essential for supporting their growth. Within the recruited microbes, some taxa are consistently enriched in the rhizosphere across various locations and crop genotypes, while others are unique to specific planting sites or genotypes. Whether these differentially enriched taxa are different in community composition and how they interact with nutrient cycling need further investigation. Here, we sampled bulk soil and the rhizosphere soil of five soybean varieties grown in Shijiazhuang and Xuzhou, categorized the rhizosphere-enriched microbes into shared, site-specific, and variety-specific taxa, and analyzed their correlation with the diazotrophic communities and microbial genes involved in nitrogen (N) cycling. The shared taxa were dominated by Actinobacteria and Thaumarchaeota, the site-specific taxa were dominated by Actinobacteria in Shijiazhuang and by Nitrospirae in Xuzhou, while the variety-specific taxa were more evenly distributed in several phyla and contained many rare operational taxonomic units (OTUs). The rhizosphere-enriched taxa correlated with most diazotroph orders negatively but with eight orders including Rhizobiales positively. Each group within the shared, site-specific, and variety-specific taxa negatively correlated with bacterial amoA and narG in Shijiazhuang and positively correlated with archaeal amoA in Xuzhou. These results revealed that the shared, site-specific, and variety-specific taxa are distinct in community compositions but similar in associations with rhizosphere N-cycling functions. They exhibited potential in regulating the soybean roots' selection for high-efficiency diazotrophs and the ammonia-oxidizing and denitrification processes. This study provides new insights into soybean rhizosphere-enriched microbes and their association with N cycling. KEY POINTS: • Soybean rhizosphere affected diazotroph community and enriched nifH, amoA, and nosZ. • Shared and site- and variety-specific taxa were dominated by different phyla. • Rhizosphere-enriched taxa were similarly associated with N-cycle functions.

Landscape and conservation genetics of western black crested gibbons (Nomascus concolor) in China.

Despite decades of field study, very little is known about the molecular ecology of gibbons, particularly as it relates to their ability to disperse across degraded and fragmentary landscapes. The critically endangered western black crested gibbon (Nomascus concolor) has been reduced to a small, fragmented population with about 1300 individuals. In the largest population genetic study of free-ranging gibbons to date, we sampled 47 of these gibbons from 13 sites in China and generated 15 polymorphic autosomal microsatellite markers. We identify three population clusters of N. concolor in Yunnan centered in 1) the Wuliang and Ailao Mountains, 2) the Yongde Daxueshan Mountains, and 3) an isolated remnant near the border with Vietnam. Within the Wuliang Mountains, we identified four subclusters, three of which are bounded by high-altitude rhododendron forest, and one that is isolated from the main population by ~2 km of degraded forest and pasture. Least-cost path analysis and isolation by resistance modeling demonstrates that the population genetic distances among gibbons in Wuliangshan National Nature Reserve are significantly correlated with geographic paths that avoid use of high-altitude rhododendron forest in favor of evergreen broadleaf forest. Although these gibbons have likely undergone reductions in heterozygosity from recent consanguineous mating, we suggest that their active avoidance of inbreeding on the population level maintains higher than expected levels of genetic diversity. This research provides new insights into how gibbons interact with heterogeneous environments and expands our understanding of their molecular ecology and conservation genetics.

Long-term carbaryl exposure leads to behavioral abnormalities and reproductive toxicity in male marine medaka through apoptosis-mediated HPA and HPG axes dysregulation.

Carbaryl is a widely used carbamate pesticide that has been detected in the marine environment, but its effects on marine fish are still unknown. This study was aimed to investigate the effects of long-term exposure of carbaryl on male marine medaka. For this purpose, we set up five exposure concentration groups of 0, 0.1, 1, 10, and 100 µg/L for 180 days. On the one hand, we observed increased aggression and decreased ability to avoid predators in males after exposure, which was affected by the levels of HPA-axis hormones, especially decreased cortisol level. On the other hand, after exposure, HPG axis hormone levels and gene transcription levels were disturbed. Males exhibited a decreased gonadosomatic index and a notable reduction in mature sperm proportion and the F1 generation displayed a significant increase in malformation rate. Additionally, the number of apoptotic cells and the transcription level of apoptosis-related genes in the brains of male marine medaka substantially increased after exposure. Apoptosis of brain cells may be responsible for the disturbance of HPA and HPG axes, consequently leading to behavioral and reproductive abnormalities. These findings provide novel insights into evaluating the toxic effects of carbaryl on male marine medaka and emphasizing the criticality of exploring the potential environmental risks posed by carbaryl in the marine environment, thus providing toxicity value basis for further strengthening marine environmental monitoring and the protection of biological resources.

CX43 and oxidative stress are the targets of BCB staining to predict the developmental potential of buffalo oocytes.

This study used the brilliant cresyl blue (BCB) staining method to group buffalo oocytes (BCB+ and BCB-) and perform in vitro maturation, in vitro fertilization and embryo culture. At the same time, molecular biology techniques were used to detect gap junction protein expression and oxidative stress-related indicators to explore the molecular mechanism of BCB staining to predict oocyte developmental potential. The techniques of buffalo oocytes to analyse their developmental potential and used immunofluorescence staining to detect the expression level of CX43 protein, DCFH-DA probe staining to detect ROS levels and qPCR to detect the expression levels of the antioxidant-related genes SOD2 and GPX1. Our results showed that the in vitro maturation rate, embryo cleavage rate and blastocyst rate of buffalo oocytes in the BCB+ group were significantly higher than those in the BCB- group and the control group (p < .05). The expression level of CX43 protein in the BCB+ group was higher than that in the BCB- group both before and after maturation (p < .05). The intensity of ROS in the BCB+ group was significantly lower than that in the BCB- group (p < .05), and the expression levels of the antioxidant-related genes SOD2 and GPX1 in the BCB+ group were significantly higher than those in the BCB- group (p < .05). Brilliant cresyl blue staining could effectively predict the developmental potential of buffalo oocytes. The results of BCB staining were positively correlated with the expression of gap junction protein and antioxidant-related genes and negatively correlated with the reactive oxygen species level, suggesting that the mechanism of BCB staining in predicting the developmental potential of buffalo oocytes might be closely related to antioxidant activity.

High-Efficiency Photo-Fenton-like Catalyst of FeOOH/g-C3N4 for the Degradation of PNP: Characterization, Catalytic Performance and Mechanism Exploration.

The composite photocatalyst FeOOH/g-C3N4 was prepared through thermal polycondensation and co-precipitation methods, followed by XRD, SEM and UV-vis characterization. The stability of FeOOH/g-C3N4 was explored by the recycling test. The active species in the reaction system were investigated by the capture experiment. The results indicated that the optimal preparation condition for g-C3N4 involved calcination at 600 °C for 4 h. XRD analysis revealed that g-C3N4 exhibits a high-purity phase, and Fe in FeOOH/g-C3N4 exists in a highly dispersed amorphous state. SEM analysis showed that FeOOH/g-C3N4 has a rough surface with an irregular layered structure. Element composition analysis confirmed that the content of elements in the prepared catalyst is consistent with the theoretical calculation. FeOOH/g-C3N4 possesses the largest specific surface area of 143.2 m2/g and a suitable pore distribution. UV-vis DRS analysis showed that the absorption intensity of FeOOH/g-C3N4 is stronger than that of g-C3N4. When the catalyst dosage was 1.0 g/L, the H2O2 dosage was 4 mmol/L, the PNP initial concentration was 10 mg/L and the initial pH value was 5, the PNP removal could reach 92% in 120 min. Even after 5 cycles, the efficiency of PNP removal by FeOOH/g-C3N4 remains nearly 80%. The capture experiment indicated that both •OH and •O2- play roles in the photocatalytic degradation of PNP, with •OH being more significant. These findings affirm that FeOOH has been successfully incorporated into g-C3N4, resulting in a conspicuous catalytic effect on the degradation of PNP in the visible light-assisted Fenton-like reaction.

A Novel Quercetin Encapsulated Glucose Modified Liposome and Its Brain-Target Antioxidative Neuroprotection Effects.

Neurodegenerative diseases (NDDs) are mainly induced by oxidative stress which produces excessive reactive oxygen species (ROS). Quercetin (QU) is a potent antioxidant with some effects on NDDs. This study prepared and characterized a novel glucose-modified QU liposome (QU-Glu-Lip), aiming not only to overcome QU's poor water solubility and bioavailability but also to deliver more QU to brain tissue to enhance its neuroprotective effect. QU-Glu-Lip possessed encapsulation efficiency (EE) of 89.9%, homogenous particle sizes (116-124 nm), small PDI value (<0.3), zeta value -1.363 ± 0.437 mV, proper pH and salt stability, and proper cytotoxicity. The glucose-modified liposome penetrated the blood-brain barrier (BBB) mediated via the glucose transporter 1 (GLUT1) and was taken by neuronal cells more efficiently than liposome without glucose, according to bEnd.3 and PC12 cell tests. QU-Glu-Lip attenuated H2O2-induced oxidative damage to PC12 with higher cell viability (88.42%) and lower intracellular ROS compared to that of QU. QU-Glu-Lip had higher brain target ability and delivered more QU to neuronal cells, effectively exerting the antioxidative neuroprotection effect. There is potential for the QU-Glu-Lip application for more effective treatment of NDDs.

Longitudinal Relationships Between School Climate, Academic Achievement, and Gaming Disorder Symptoms Among Chinese Adolescents.

Despite growing concerns regarding the development of gaming disorder symptoms among adolescents, the longitudinal relationship between school factors and gaming disorder symptoms remains far from being fully understood. This two-year longitudinal study examined the relationship between school climate perceptions, academic achievement, and gaming disorder symptoms among three distinct demographic cohorts: preadolescents (n = 1513; 46.9% girls, Mage = 10.64 years, SD = 0.56), early adolescents (n = 1771; 48.3% girls, Mage = 13.54 years, SD = 0.70), and late adolescents (n = 2385; 50.1% girls, Mage = 16.41 years, SD = 0.59). A four-wave study was conducted (six months apart) using random intercept cross-lagged panel models (RI-CLPMs) to separate the within-person (state level) from the between-person (trait level) effects. The results obtained from the RI-CLPMs indicated that fluctuations in school climate perceptions negatively predicted subsequent changes in gaming disorder symptoms among preadolescents at the within-person level, but not among early and late adolescents. Fluctuations relating to gaming disorder symptoms also negatively predicted subsequent changes regarding academic achievement in late adolescents, but not in preadolescents and early adolescents. The effect of school-related factors on gaming disorder symptoms varies across different developmental stages. While preadolescents may represent a particularly susceptible subgroup for gaming disorder in terms of being predicted by their school environment, late adolescents appear to be more vulnerable to predictors of gaming disorder symptoms. The current study also discusses the implications of school-wide programs aimed at improving school climate and preventing the development of gaming disorder symptoms during key developmental periods.

Long-term exposure to aryl hydrocarbon receptor agonist neburon induces reproductive toxicity in male zebrafish (Danio rerio).

Neburon is a phenylurea herbicide that is widely used worldwide, but its toxicity is poorly studied. In our previous study, we found that neburon has strong aryl hydrocarbon receptor (AhR) agonist activity, but whether it causes reproductive toxicity is not clear. In the present study, zebrafish were conducted as a model organism to evaluate whether environmental concentrations of neburon (0.1, 1 and 10 µg/L) induce reproductive disorder in males. After exposure to neburon for 150 days from embryo to adult, that the average spawning egg number in high concentration group was 106.40, which was significantly lower than 193.00 in control group. This result was mainly due to the abnormal male reproductive behavior caused by abnormal transcription of genes associated with reproductive behavior in the brain, such as secretogranin-2a. The proportions of spermatozoa in the medium and high concentration groups were 82.40% and 83.84%, respectively, which were significantly lower than 89.45% in control group. This result was mainly caused by hormonal disturbances and an increased proportion of apoptotic cells. The hormonal disruption was due to the significant changes in the transcription levels of key genes in the hypothalamus-pituitary-gonadal axis following neburon treatment. Neburon treatment also significantly activated the AhR signaling pathway, causing oxidative stress damage and eventually leading to a significant increase in apoptosis in the exposed group. Together, these data filled the currently more vacant profile of neburon toxicity and might provide information to assess the ecotoxicity of neburon on male reproduction at environmentally relevant concentrations.

Early diagnosis of aspiration pneumonia by gastrointestinal ultrasound combined with lung ultrasound.

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Numerical Investigation on Precipitation Hardening of Mg-Gd Alloys.

The second-phase particles in magnesium alloys could affect the mechanical properties of the material significantly. In this work, 3D finite element models with explicit incorporation of second-phase particles are established. The simulations are calibrated with the experimental results of the Mg-1Gd alloy. The influences of factors, such as the particle distribution, size, and orientation of cylindrical particles, on precipitation hardening are investigated in detail. Three interface conditions between particles and the matrix-perfect bonding and high- and low-strength bonding-are studied at the same time. The interface conditions are shown to exert a stronger influence on precipitation hardening compared to the factors of particle distribution and size. In contrast, the influence of the orientation of cylindrical particles at grain boundaries outweighs the effect of interface property. When second-phase particles are relatively large and all located at grain boundaries, the hardening effect can be improved, and the magnesium alloy shows relatively high flow stress. However, the high hardening effect from the second-phase particles could result in high local stress concentration and possible early failure or low ductility of Mg alloys.

Efficacy of Acupuncture in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Purpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD. Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: -3.25; 95% CI: -3.73 to -2.78, P<0.001) and arterial blood gas (PaCO2: MD: -1.85; 95% CI: -2.74 to -0.95, P<0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P<0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: -0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: -0.60 to 193.98, P = 0.051), hospitalization duration (MD: -5.70; 95% CI: -11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: -0.19; 95% CI: -0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in "high" risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in "some concern" and 1 RCT assessing hospitalization duration was in "low" risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported. Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.

Inhibition of insulin fibrillation by carboxyphenylboronic acid-modified chitosan oligosaccharide based on electrostatic interactions and hydrophobic interactions.

A novel inhibitor, carboxyphenylboronic acid-modified chitosan oligosaccharide (COS-CPBA), was developed by coupling carboxyphenylboronic acid (CPBA) with chitosan oligosaccharide (COS) to inhibit insulin fibrillation. Extensive biophysical assays indicated that COS-CPBA could decelerate insulin aggregation, hinder the conformational transition from α-helix to ß-sheet structure, change the morphology of insulin aggregates and alter fibrillation pathway. A mechanism for the inhibition of insulin fibrillation by COS-CPBA was proposed. It considers that insulin molecules bind to COS-CPBA via hydrophobic interactions, while the positively charged groups in COS-CPBA exert electrostatic repulsion on the bound insulin molecules. These two opposite forces cause the insulin molecules to display extended conformations and hinder the conformational transition of insulin from α-helix to ß-sheet structure necessary for fibrillation, thus decelerating aggregation and altering the fibrillation pathway of insulin. The studies provide novel ideas for the development of more effective inhibitors of amyloid fibrillation.

Metformin alleviates junctional epithelium senescence via the AMPK/SIRT1/autophagy pathway in periodontitis induced by hyperglycemia.

The junctional epithelium (JE) serves a crucial protective role in the periodontium. High glucose-related aging results in accelerated barrier dysfunction of the gingival epithelium, which may be associated with diabetic periodontitis. Metformin, an oral hypoglycemic therapeutic, has been proposed as a anti-aging agent. This study aimed to clarify the effect of metformin on diabetic periodontitis and explore its mechanism in ameliorating senescence of JE during hyperglycemia. The db/db mice was used as a diabetic model mice and alterations in the periodontium were observed by hematoxylin-eosin staining and immunohistochemistry. An ameloblast-like cell line (ALC) was cultured with high glucose to induce senescence. Cellular senescence and oxidative stress were evaluated by SA-ß-gal staining and Intracellular reactive oxygen species (ROS) levels. Senescence biomarkers, P21 and P53, and autophagy markers, LC3-II/LC3-I, were measured by western blotting and quantitative real-time PCR. To construct a stable SIRT1 (Sirtuin 1) overexpression cell line, we transfected ALCs with lentiviral vectors overexpressing the mouse SIRT1 gene. Cellular senescence was increased in the JE of db/db mice and the periodontium was destroyed, which could be alleviated by metformin. Moreover, oxidative stress and cellular senescence in a high glucose environment were reduced by metformin in in-vitro assays. The autophagy inhibitor 3-MA and SIRT1 inhibitor EX-527 could dampen the effects of metformin. Overexpression of SIRT1 resulted in increased autophagy and decreased oxidative stress and cellular senescence. Meanwhile, AMPK (AMP-activated protein kinase) inhibition reversed the anti-senescence effects of metformin. Overall, these results suggest that metformin alleviates periodontal damage in db/db mice and cellular senescence in ALCs under high glucose conditions via the AMPK/SIRT1/autophagy pathway.

BmSPP is a virus resistance gene in Bombyx mori.

Introduction: Signal peptide peptidase (SPP) is an intramembrane protease involved in a variety of biological processes, it participates in the processing of signal peptides after the release of the nascent protein to regulate the endoplasmic reticulum associated degradation (ERAD) pathway, binds misfolded membrane proteins, and aids in their clearance process. Additionally, it regulates normal immune surveillance and assists in the processing of viral proteins. Although SPP is essential for many viral infections, its role in silkworms remains unclear. Studying its role in the silkworm, Bombyx mori , may be helpful in breeding virus-resistant silkworms. Methods: First, we performed RT-qPCR to analyze the expression pattern of BmSPP. Subsequently, we inhibited BmSPP using the SPP inhibitor 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucylaminopropanone ((Z-LL)2-ketone) and downregulated the expression of BmSPP using CRISPR/Cas9 gene editing. Furthermore, we assessed the impact of these interventions on the proliferation of Bombyx mori nucleopolyhedrovirus (BmNPV). Results: We observed a decreased in the expression of BmSPP during viral proliferation. It was found that higher concentration of the inhibitor resulted in greater inhibition of BmNPV proliferation. The down-regulation of BmSPP in both in vivo and in vitro was found to affect the proliferation of BmNPV. In comparison to wild type silkworm, BmSPPKO silkworms exhibited a 12.4% reduction in mortality rate. Discussion: Collectively, this work demonstrates that BmSPP plays a negative regulatory role in silkworm resistance to BmNPV infection and is involved in virus proliferation and replication processes. This finding suggests that BmSPP servers as a target gene for BmNPV virus resistance in silkworms and can be utilized in resistance breeding programs.