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Abstract Background Mutton quality is closely related to genetic variants and gene expression alterations during growth and development, resulting in differences in nutritional values, flavor, and odor. Results We first evaluated and compared the composition of crude protein, crude fat, cholesterol, amino acid (AA), and fatty acid (FA) in the longissimus dorsi muscle of Guizhou black goats (GZB, n = 5) and Yunshang black goats (YBG, n = 6). The contents of cholesterol and FA related to odor in GZB were significantly lower than that in YBG, while the concentrations of umami amino acids and intramuscular fat were significantly higher in GZB. Furthermore, structural variants (SVs) in the genomes of GZB (n = 30) and YBG (n = 11) were explored. It was found that some regions in Chr 10/12/18 were densely involved with a large number of SVs in the genomes of GZB and YBG. By setting F ST ≥ 0.25, we got 837 stratified SVs, of which 25 SVs (involved in 12 genes, e.g., CORO1A, CLIC6, PCSK2, and TMEM9) were limited in GZB. Functional enrichment analysis of 14 protein-coding genes (e.g., ENPEP, LIPC, ABCA5, and SLC6A15) revealed multiple terms and pathways related with metabolisms of AA, FA, and cholesterol. The SVs (n = 10) obtained by the whole genome resequencing were confirmed in percentages of 36.67 to 86.67% (n = 96) by PCR method. The SVa and SVd polymorphisms indicated a moderate negative correlation with HMGCS1 activity (n = 17). Conclusion This study is the first to comprehensively reveal potential SVs related to mutton nutritional values, flavor, and odor based on genomic compare between two black goat breeds with closely genetic relationship. The SVs generated in this study provide a data resource for deeper studies to understand the genomic characteristics and possible evolutionary outcomes with better nutritional values, flavor and extremely light odor.

Although there have been many recent taxonomic revisions and large-scale faunistic surveys focusing on spiders from Jiangxi Province, many taxa still remain unknown, such as the Anyphaenidae spiders. Therefore, none of the anyphaenid species has been recorded from this Province.Anyphaenidae spiders were collected from Jinggangshan National Nature Reserve, Jiangxi Province, China, during the past ten years. A new tube spider species, Anyphaena leidashi Yao & Liu, sp. nov. is diagnosed, described and illustrated. Moreover, three species including A. mogan Song & Chen, 1987, A. wuyi Zhang, Zhu & Song, 2005 and Rathalos xiushanensis (Song & Zhu, 1991) are recorded from Jiangxi Province for the first time. Distributions records are given for all investigated species.

Abstract Copy number variation (CNV) tends to occur in genetically enriched regions and is likely associated with a number of complex diseases such as skin aging. In this study, we investigated the genome-wide CNVs in 20 wrinkled skin cases (WSC) of Xiang pigs and 63 controls, and identified 7893 copy number variable regions (CNVRs). We estimated the F-statistic (Fst) at each locus and identified that 93 case-controls stratified CNVRs (Fst > = 0.15) overlapped with 87 known genes. Functional enrichment analysis showed that most of these genes were predominantly enriched in pathways and terms related to the extracellular matrix. Finally, we found that some CNVs were predicted to have high effects on genes such as VCAN, TIMP1 and FOXO1 through transcriptional amplification, transcript ablation and so on. Most of the genes overlapped with those CNVRs have been reported to be related to aging in human or animals. The copy numbers presented the positive correlations with the transcript level of the genes in skins between the cases and controls. Our results suggested that those 22 CNVRs, including 19 CNV losses and 3 CNV gains, were putatively associated with the skin wrinkle of Xiang pigs.

Abstract Background Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. Method Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. Results A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507–0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116–1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425–0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135–0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322–0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells

Abstract In this study, we compared the transcriptome of longissimus dorsi muscle between Guizhou Xiang pigs (XP) and Western commercial Large White pigs (LW), which show diffirent meat quality between them. In terms of meat quality traits, the pH 45 min, color score, backfat thickness, and intramuscular fat (IMF) content were higher in Xiang pigs than in Large White pigs (P

African swine fever (ASF) is a rapidly fatal viral haemorrhagic fever in Chinese domestic pigs. Although very high mortality is observed in pig farms after an ASF outbreak, clinically healthy and antibody-positive pigs are found in those farms, and viral detection is rare from these pigs. The ability of pigs to resist ASF viral infection may be modulated by host genetic variations. However, the genetic basis of the resistance of domestic pigs against ASF remains unclear. We generated a comprehensive set of structural variations (SVs) in a Chinese indigenous Xiang pig with ASF-resistant (Xiang-R) and ASF-susceptible (Xiang-S) phenotypes using whole-genome resequencing method. A total of 53,589 nonredundant SVs were identified, with an average of 25,656 SVs per individual in the Xiang pig genome, including insertion, deletion, inversion and duplication variations. The Xiang-R group harboured more SVs than the Xiang-S group. The F-statistics (FST) was carried out to reveal genetic differences between two populations using the resequencing data at each SV locus. We identified 2,414 population-stratified SVs and annotated 1,152 Ensembl genes (including 986 protein-coding genes), in which 1,326 SVs might disturb the structure and expression of the Ensembl genes. Those protein-coding genes were mainly enriched in the Wnt, Hippo, and calcium signalling pathways. Other important pathways associated with the ASF viral infection were also identified, such as the endocytosis, apoptosis, focal adhesion, Fc gamma R-mediated phagocytosis, junction, NOD-like receptor, PI3K-Akt, and c-type lectin receptor signalling pathways. Finally, we identified 135 candidate adaptive genes overlapping 166 SVs that were involved in the virus entry and virus-host cell interactions. The fact that some of population-stratified SVs regions detected as selective sweep signals gave another support for the genetic variations affecting pig resistance against ASF. The research indicates that SVs play an important role in the evolutionary processes of Xiang pig adaptation to ASF infection.

BackgroundPrevious studies showed the conflicting associations between circulating micronutrient levels and systemic lupus erythematosus (SLE). Therefore, we aimed to clarify the causal association between circulating micronutrient levels and the risk of SLE by two-sample Mendelian randomization (MR) analysis.Methods56 single nucleotide polymorphisms (SNPs) significantly associated with 14 circulating micronutrients (vitamin A, B6, B9, B12, C, D and E, phosphorus, calcium, magnesium, copper, iron, zinc, and selenium) in published genome-wide association studies (GWAS) were used as instrumental variables (IVs). And summary statistics related to SLE were obtained from the IEU OpenGWAS database. We used the MR Steiger test to estimate the possible causal direction between circulating micronutrients and SLE. In the MR analysis, inverse variance weighting (IVW) method and the Wald ratio was as the main methods., Moreover, the MR-Pleiotropy residuals and outliers method (MR-PRESSO), Cochrane’s Q-test, MR-Egger intercept method and leave-one-out analyses were applied as sensitivity analyses. Additionally, we conducted a retrospective analysis involving the 20,045 participants from the Third National Health and Nutritional Examination Survey (NHANES III). Weight variables were provided in the NHANES data files. Univariate and multivariate logistic regression analyses were performed to determine the associations between circulating micronutrients and SLE.ResultsThe MR estimates obtained from the IVW method revealed potential negative correlations between circulating calcium (OR: 0.06, 95% CI: 0.01–0.49, P = 0.009), iron levels (OR: 0.63, 95% CI: 0.43–0.92, P = 0.016) and the risk of SLE. The results remained robust, even under various pairs of sensitivity analyses. Our retrospective analysis demonstrated that the levels of vitamin D, serum total calcium, and serum iron were significantly lower in SLE patients (N = 40) when compared to the control group (N = 20,005). Multivariate logistic regression analysis further established that increased levels of vitamin D and serum total calcium served as protective factors against SLE.ConclusionOur results provided genetic evidence supporting the potential protective role of increasing circulating calcium in the risk of SLE. Maintaining adequate levels of calcium may help reduce the risk of SLE.

Abstract Background Guizhou black goat is one of the indigenous black goat breeds in the southwest region of Guizhou, China, which is an ordinary goat for mutton production. They are characterized by moderate body size, black coat, favorite meat quality with tender meat and lower odor, and tolerance for cold and crude feed. However, little is known about the genetic characteristics or variations underlying their important economic traits. Results Here, we resequenced the whole genome of Guizhou black goat from 30 unrelated individuals breeding in the five core farms. A total of 9,835,610 SNPs were detected, and 2,178,818 SNPs were identified specifically in this breed. The population structure analysis revealed that Guizhou black goat shared a common ancestry with Shaanbei white cashmere goat (0.146), Yunshang black goat (0.103), Iran indigenous goat (0.054), and Moroccan goat (0.002). However, Guizhou black goat showed relatively higher genetic diversity and a lower level of linkage disequilibrium than the other seven goat breeds by the analysis of the nucleotide diversity, linkage disequilibrium decay, and runs of homozygosity. Based on F ST and θπ values, we identified 645, 813, and 804 selected regions between Guizhou black goat and Yunshang black goat, Iran indigenous goat, and cashmere goats. Combined with the results of XP-EHH, there were 286, 322, and 359 candidate genes, respectively. Functional annotation analysis revealed that these genes are potentially responsible for the immune response (e.g., CD28, CD274, IL1A, TLR2, and SLC25A31), humility-cold resistance (e.g., HBEGF, SOSTDC1, ARNT, COL4A1/2, and EP300), meat quality traits (e.g., CHUK, GAB2, PLAAT3, and EP300), growth (e.g., GAB2, DPYD, and CSF1), fertility (e.g., METTL15 and MEI1), and visual function (e.g., PANK2 and NMNAT2) in Guizhou black goat. Conclusion Our results indicated that Guizhou black goat had a high level of genomic diversity and a low level of linkage disequilibrium in the whole genome. Selection signatures were detected in the genomic regions that were mainly related to growth and development, meat quality, reproduction, disease resistance, and humidity-cold resistance in Guizhou black goat. These results would provide a basis for further resource protection and breeding improvement of this very local breed.

Abstract Background Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional. Methods A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method. Results In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. Conclusion Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

BackgroundCardiovascular diseases (CVD) and type 2 diabetes (T2D) account for the majority of the burden of noncommunicable disease caused by low physical activity (LPA). In order to inform future interventions, this study aims to assess the burden and trends in mortality and disability-adjusted life years (DALYs) of CVD and T2D attributable to LPA by year, location, sex, and age from 1990 to 2019.MethodsMortality, DALYs, and their age-standardised rates (ASMR, ASDR) for CVD and T2D attributable to LPA were retrieved from Global Burden of Disease (GBD) 2019. The estimated annual percentage changes (EAPCs) were calculated using linear regression model to describe the trend over time.ResultsFrom 1990 to 2019, the number of deaths caused by both CVD and T2D due to LPA increased significantly globally. However, the overall ASMR and ASDR for CVD declined over this same period [EAPC for ASMR (CVD) = −1.44 (95% CI: −1.50–1.38), EAPC for ASDR (CVD) = −1.30 (95% CI: −1.35 to −1.25)]. In terms of disparities, ASMR (CVD) and ASDR (CVD) in North Africa and the Middle East were consistently higher than the global average; also, the sex difference in ASMR was greatest in Central Asia. ASMR among people aged 25–44 in high Socio-Demographic Index (SDI) region has increased significantly over the past three decades. ASMR (T2D) due to LPA showed an increasing trend year by year, with EAPC = 0.26 (95% CI: 0.13–0.39), and this rate increased faster in males than in females. Consistent with cardiovascular diseases, ASMR of type 2 diabetes attributable to LPA increased among people aged 25–44, while decreased in other age groups in high SDI region.ConclusionInterventions targeting LPA are warranted in controlling the burden of cardiovascular diseases and type 2 diabetes. Countries should adapt strategies to their local contexts, considering the sex and age differences among their populations. The 25–44 age group should be given special attention to prevent the disease burden from worsening among younger people.

Abstract Xiang pig (XP) is one of the best-known indigenous pig breeds in China, which is characterized by its small body size, strong disease resistance, high adaptability, favorite meat quality, small litter sizes, and early sexual maturity. However, the genomic evidence that links these unique traits of XP is still poorly understood. To identify the genomic signatures of selection in XP, we performed whole-genome resequencing on 25 unrelated individual XPs. We obtained 876.70 Gb of raw data from the genomic libraries. The LD analysis showed that the lowest level of linkage disequilibrium was observed in Xiang pig. Comparative genomic analysis between XPs and other breeds including Tibetan, Meishan, Duroc and Landrace revealed 3062, 1228, 907 and 1519 selected regions, respectively. The genes identified in selected regions of XPs were associated with growth and development processes (IGF1R, PROP1, TBX19, STAC3, RLF, SELENOM, MSTN), immunity and disease resistance (ZCCHC2, SERPINB2, ADGRE5, CYP7B1, STAT6, IL2, CD80, RHBDD3, PIK3IP1), environmental adaptation (NR2E1, SERPINB8, SERPINB10, SLC26A7, MYO1A, SDR9C7, UVSSA, EXPH5, VEGFC, PDE1A), reproduction (CCNB2, TRPM6, EYA3, CYP7B1, LIMK2, RSPO1, ADAM32, SPAG16), meat quality traits (DECR1, EWSR1), and early sexual maturity (TAC3). Through the absolute allele frequency difference (ΔAF) analysis, we explored two population-specific missense mutations occurred in NR6A1 and LTBP2 genes, which well explained that the vertebrae numbers of Xiang pigs were less than that of the European pig breeds. Our results indicated that Xiang pigs were less affected by artificial selection than the European and Meishan pig breeds. The selected candidate genes were mainly involved in growth and development, disease resistance, reproduction, meat quality, and early sexual maturity. This study provided a list of functional candidate genes, as well as a number of genetic variants, which would provide insight into the molecular basis for the unique traits of Xiang pig.

Abstract Background The fecundity of sows is a trait of major economic in pig industry. The molecular regulation of estrus cycles can affect the fecundity of female animals. Compared with the other pig breeds, Xiang pig exhibits the special estrus behaviors. CircRNAs are thought to involve in regulation of multiple biological processes. However, the potential roles of circRNAs in ovary regulation on Xiang pig estrus are largely unknown. Results 8,937 circRNAs were identified from eight libraries constructed from the ovarian samples of Xiang pig at estrus and diestrus stages by RNA sequencing method. Of which, 1,995 were high confidence circRNAs detected at least two junction reads in each ovary sample and seven circRNAs were validated by RT-PCR method. Furthermore, we identified 290 upregulated and 15 downregulated circRNAs in estrus ovaries. These differentially expressed circRNAs (DECs) derived from 273 host genes. And 207 miRNAs were identified to be targets sponged by 156 DECs with 432 binding sites, containing more than one miRNA binding site in each circRNA. Function enrichment analysis revealed that the host genes and the targets of miRNAs sponged by DECs were enriched in several reproduction-related signaling pathways, such as ovarian steroidogenesis, oocyte maturation, circadian rhythm, estrogen signaling pathway, GnRH signaling pathway, circadian entrainment, and oocyte meiosis. The circRNA-miRNA-mRNA networks revealed that 153 miRNAs interacting with 122 DECs and 86 miRNAs interacting with 84 DECs were involved in ovarian functions and ovarian circadian entrainment and circadian rhythm respectively. The DEC-miRNA-DEG (differentially expressed gene, DEG) networks associated with reproduction-related signaling pathways contained 22 DECs,18 miRNAs and 7 DEGs. 22 DECs were recognized as hub circRNAs during the estrus phase of Xiang pigs. Conclusions The circRNAs that function as miRNA sponges could play a key role in post-transcriptional regulation of gene expression during Xiang pig’s estrus cycle.

Measurement(s) Metagenome-assembled genomes Technology Type(s) Metagenomics Sample Characteristic - Organism Bacteria • Archaea Sample Characteristic - Environment estuarine water Sample Characteristic - Location South China Sea coastal waters of the mainland of China

Abstract Background Although lots of quantitative trait loci (QTLs) and genes present roles in litter size of some breeds, the information might not make it clear for the huge diversity of reproductive capability in pig breeds. To elucidate the inherent mechanisms of heterogeneity of reproductive capability in litter size of Xiang pig, we performed transcriptome analysis for the expression profile in ovaries using RNA-seq method. Results We identified 1,419 up-regulated and 1,376 down-regulated genes in Xiang pigs with large litter size. Among them, 1,010 differentially expressed genes (DEGs) were differently spliced between two groups with large or small litter sizes. Based on GO and KEGG analysis, numerous members of genes were gathered in ovarian steroidogenesis, steroid biosynthesis, oocyte maturation and reproduction processes. Conclusions Combined with gene biological function, twelve genes were found out that might be related with the reproductive capability of Xiang pig, of which, eleven genes were recognized as hub genes. These genes may play a role in promoting litter size by elevating steroid and peptide hormones supply through the ovary and facilitating the processes of ovulation and in vivo fertilization.

Innovative product design is the core problem of modern industry and the source power of enterprise development. With the continuous improvement of China’s material level, product innovation design has changed from functional needs to emotional needs, and the product design method centered on users’ emotional needs has attracted much attention. With the emergence of new technologies such as artificial intelligence and big data, the automation and intelligence of advanced algorithms and innovative design methods for online product decision driven by multimodal multimedia data in e-commerce have become inevitable trends in the field of product design, and it is a big challenge to improve the innovative design ability of products by using information technology. In order to solve this problem, based on the research of BP neural network technology, this paper puts forward an innovative product design method based on image-Kempi method. The color features of images are reconstructed and integrated, and then transferred to product modeling, so as to generate new products with both content image modeling features and style image color features, which brings visual inspiration to users. The results show that KENPI method combines the theories of Kansei engineering, convolutional neural network, and neural style transfer, and establishes a mapping model between product modeling elements and product semantics. Convolutional neural network and neural style transfer model are used to extract, reconstruct, and integrate the color features of style diagrams, and transfer them to product modeling to design new product images. By evaluating the image quality and comparing the product semantics before and after the migration, the validity and feasibility of the migration are verified. Based on BP neural network, a nonlinear mapping model between product attribute space and product semantic space is constructed, and the generalization ability of the model is evaluated, which verifies the feasibility and effectiveness of this method. The research results have important theoretical guiding significance for improving the innovative design ability of enterprises, enhancing product competitiveness, and customer satisfaction.

Drug use and abuse are complex issues in that the basis of each may involve different determinants and consequences, and the transition from one to the other may be equally multifaceted. A recent model of the addiction cycle (as proposed by Koob and his colleagues) illustrates how drug-taking patterns transition from impulsive (acute use) to compulsive (chronic use) as a function of various neuroadaptations leading to the downregulation of DA systems, upregulation of stress systems, and the dysregulation of the prefrontal/orbitofrontal cortex. Although the nature of reinforcement in the initiation and mediation of these effects may differ (positive vs. negative), the role of reinforcement in drug intake (acute and chronic) is well characterized. However, drugs of abuse have other stimulus properties that may be important in their use and abuse. One such property is their aversive effects that limit drug intake instead of initiating and maintaining it. Evidence of such effects comes from both clinical and preclinical populations. In support of this position, the present review describes the aversive effects of drugs (assessed primarily in conditioned taste aversion learning), the fact that they occur concurrently with reward as assessed in combined taste aversion/place preference designs, the role of aversive effects in drug-taking (in balance with their rewarding effects), the dissociation of these affective properties in that they can be affected in different ways by the same manipulations, and the impact of various parametric, experiential, and subject factors on the aversive effects of drugs and the consequent impact of these factors on their use and abuse potential.

Skeletal muscle is the most abundant tissue in mammals, and myogenesis and differentiation require a series of regulatory factors such as microRNAs (miRNAs). In this study, we found that miR-103-3p was highly expressed in the skeletal muscle of mice, and the effects of miR-103-3p on skeletal muscle development were explored using myoblast C2C12 cells as a model. The results showed that miR-103-3p could significantly reduce myotube formation and restrain the differentiation of C2C12 cells. Additionally, miR-103-3p obviously prevented the production of autolysosomes and inhibited the autophagy of C2C12 cells. Moreover, bioinformatics prediction and dual-luciferase reporter assays confirmed that miR-103-3p could directly target the microtubule-associated protein 4 (MAP4) gene. The effects of MAP4 on the differentiation and autophagy of myoblasts were then elucidated. MAP4 promoted both the differentiation and autophagy of C2C12 cells, which was contrary to the role of miR-103-3p. Further research revealed that MAP4 colocalized with LC3 in C2C12 cell cytoplasm, and the immunoprecipitation assay showed that MAP4 interacted with autophagy marker LC3 to regulate the autophagy of C2C12 cells. Overall, these results indicated that miR-103-3p regulated the differentiation and autophagy of myoblasts by targeting MAP4. These findings enrich the understanding of the regulatory network of miRNAs involved in the myogenesis of skeletal muscle.

The mechanism of bacterial adaption to manganese-polluted environments was explored using 50 manganese-tolerant strains of bacteria isolated from soil of the largest manganese mine in China. Efficiency of manganese removal by the isolated strains was investigated using atomic absorption spectrophotometry. Bacillus safensis strain ST7 was the most effective manganese-oxidizing bacteria among the tested isolates, achieving up to 82% removal at a Mn(II) concentration of 2,200 mg/L. Bacteria-mediated manganese oxide precipitates and high motility were observed, and the growth of strain ST7 was inhibited while its biofilm formation was promoted by the presence of Mn(II). In addition, strain ST7 could grow in the presence of high concentrations of Al(III), Cr(VI), and Fe(III). Genome-wide analysis of the gene expression profile of strain ST7 using the RNA-seq method revealed that 2,580 genes were differently expressed under Mn(II) exposure, and there were more downregulated genes (n = 2,021) than upregulated genes (n = 559) induced by Mn stress. KAAS analysis indicated that these differently expressed genes were mainly enriched in material metabolisms, cellular processes, organism systems, and genetic and environmental information processing pathways. A total of twenty-six genes from the transcriptome of strain ST7 were involved in lignocellulosic degradation. Furthermore, after 15 genes were knocked out by homologous recombination technology, it was observed that the transporters, multicopper oxidase, and proteins involved in sporulation and flagellogenesis contributed to the removal of Mn(II) in strain ST7. In summary, B. safensis ST7 adapted to Mn exposure by changing its metabolism, upregulating cation transporters, inhibiting sporulation and flagellogenesis, and activating an alternative stress-related sigB pathway. This bacterial strain could potentially be used to restore soil polluted by multiple heavy metals and is a candidate to support the consolidated bioprocessing community.

Protein arginine methyltransferases 5 (PRMT5) is a clinically promising epigenetic target that is upregulated in a variety of tumors. Currently, there are several PRMT5 inhibitors under preclinical or clinical development, however the established clinical inhibitors show favorable toxicity. Thus, it remains an unmet need to discover novel and structurally diverse PRMT5 inhibitors with characterized therapeutic utility. Herein, a series of tetrahydroisoquinoline (THIQ) derivatives were designed and synthesized as PRMT5 inhibitors using GSK-3326595 as the lead compound. Among them, compound 20 (IC50: 4.2 nM) exhibits more potent PRMT5 inhibitory activity than GSK-3326595 (IC50: 9.2 nM). In addition, compound 20 shows high anti-proliferative effects on MV-4-11 and MDA-MB-468 tumor cells and low cytotoxicity on AML-12 hepatocytes. Furthermore, compound 20 possesses acceptable pharmacokinetic profiles and displays considerable in vivo antitumor efficacy in a MV-4-11 xenograft model. Taken together, compound 20 is an antitumor compound worthy of further study.

Indoor horticulture: Lighting the way to sustainability Tailored multidisciplinary approaches to hone sustainable indoor horticulture could significantly improve plant yields and crop quality. Advances in artificial lighting systems could transform commercial-scale indoor horticulture, but the current technology is limited by a lack of molecular data for plants grown under such lighting schemes. Aloysius Wong at Wenzhou-Kean University in Wenzhou, China, and co-workers reviewed research into the effects of light quality and differing wavelengths on plant growth. The team advocate the use of plant type-specific and functional genomics studies to examine light-determined molecular traits and associated gene expression. These could be used to build an extensive catalog of light qualities that enhance indoor crop yields and quality. Combining LED lights of different colors and wavelengths shows promise, and the researchers highlight the potential of tunable narrow wavelength lights, such as lasers.

Blockade of the programmed cell death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction is currently the focus in the field of cancer immunotherapy, and so far, several monoclonal antibodies (mAbs) have achieved encouraging outcomes in cancer treatment. Despite this achievement, mAbs-based therapies are struggling with limitations including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, which prompted a shift towards the development of the small-molecule inhibitors of PD-1/PD-L1 pathways. Even though many small-molecule inhibitors targeting PD-1/PD-L1 interaction have been reported, their development lags behind the corresponding mAb, partly due to the challenges of developing drug-like small molecules. Herein, we report the discovery of a series of novel inhibitors targeting PD-1/PD-L1 interaction via structural simplification strategy by using BMS-1058 as a starting point. Among them, compound A9 stands out as the most promising candidate with excellent PD-L1 inhibitory activity (IC50 = 0.93 nM, LE = 0.43) and high binding affinity to hPD-L1 (KD = 3.64 nM, LE = 0.40). Furthermore, A9 can significantly promote the production of IFN-γ in a dose-dependent manner by rescuing PD-L1 mediated T-cell inhibition in Hep3B/OS-8/hPD-L1 and CD3-positive T cells co-culture assay. Taken together, these results suggest that A9 is a promising inhibitor of PD-1/PD-L1 interaction and is worthy for further study.

In this study, we assembled the complete mitochondrial genome of Prolixicheilus longisulcus based on high-throughput Illumina sequencing. The complete mitochondrial genome of P. longisulcus was 16,598 bp in size. It was made up of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 control region. The overall base composition included A(32.38%), T(26.08%), C(26.32%) and G(15.22%). The phylogenetic tree was conducted to provide a relationship within Labeoninae based on the maximum likelihood (ML) method. The ML tree demonstrated this species had the closest relationship with Cophecheilus bamen. These results should help to better understand the phylogenetic evolution of Labeoninae.

Digital flicker detection devices need to store a large amount of evaluation data during measurement process, which leads to high requirements for hardware resources and algorithm execution efficiency. In this paper, a digital flicker detection method based on probability resampling is studied. In particular, before statistical evaluation, probability resampling is applied to screen the instantaneous flicker visual sensitivity data to compress redundant data. Additionally, the effectiveness of the method was numerically simulated and experimentally tested. The results show that the proposed method can accurately measure the voltage flicker value and can effectively compress the redundant evaluation data to be evaluated and has significant advantages in releasing hardware storage space, in improving algorithm execution efficiency and real-time performance, and in reducing processor workload. This method provides an engineering application reference for designing digital flicker detectors, especially for the software upgrade of traditional power quality testing equipment.

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Wrinkling is prominent manifestation of aging skin. A mutant phenotype characterized by systemic wrinkles and thickened skin was discovered in Xiang pig populations with incidence about 1-3%. The feature in histological structure was epidermal hyperplasia and thickening, collagen fibers disorder. To uncover genetic mechanisms for the mutant phenotype of Xiang pigs with systemic wrinkle (WXP), a genome-wide of structural variations (SVs) in WXP was described by next generation resequencing, taking Xiang pigs (XP) and European pigs (EUP) as compares. Total of 32,308 SVs were detected from three pig groups and 965 SVs were identified specifically from WXP, involving 481 protein-coding genes. These genes were mainly enriched in nuclear structure, ECM components and immunomodulatory pathways. According to gene function and enrichment analysis, we found that 65 candidate SVs in 59 protein genes were probably related with the systemic wrinkle of WXP. Of these, several genes are reported to be associate with aging, such as EIF4G2 , NOLC1 , XYLT1 , FUT8, MDM2 and so on. The insertion/deletion and duplication variations of SVs in these genes resulted in the loss of stop-codon or frameshift mutation, and aberrant alternative splicing of transcripts. These genes are involved in cell lamin filament, intermediate filament cytoskeleton, supramolecular complex, cell differentiation and regulation of macromolecule metabolic process etc. Our study suggested that the loss of function or aberrant expression of these genes lead to structural disorder of nuclear and the extracellular matrix (ECM) in skin cells, which probably was the genetic mechanisms for the mutant phenotype of systemic skin wrinkle of Xiang pig.