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Abstract Background Glaesserella parasuis (G. parasuis) is the causative agent of Glässer’s disease, which causes significant economic losses in the swine industry. However, research on the pathogenesis of G. parasuis has been hampered by the lack of a simple and efficient marker-free knockout system. Results In this study, a marker-free knockout system was developed for G. parasuis using a temperature-sensitive vector. By alternating the incubation of transformants at 30°C and 37°C, we optimized the screening process for this system. The system was successfully applied to knockout the Kan R cassette from JS0135ΔnanH::Kan R , achieving a knockout efficiency of 90% in the final round of screening. To confirm that temperature variation was a key factor, we proceeded with knocking out the nanH and apd genes in the CF7066 strain. The knockout efficiency reached up to 100%, with the shortest screening time being only four days. The knockout of the nanH gene resulted in a significant reduction in the growth vitality of the strains, while the knockout of the apd gene led to an approximate 56% improvement in the adhesion rate. Additionally, we observed that the expression of recombinant genes in transformants was higher at 30℃ than at 37℃, with the recC gene being upregulated approximately 7-fold. In contrast, there was almost no difference in the expression of recombinant genes between 30℃ and 37℃ in the wild-type strains. This discrepancy was likely due to an elevated copy number of target plasmids at 30℃, which may have resulted in the enhanced expression of recombinant genes. Conclusions In conclusion, this newly developed gene knockout system for G. parasuis presents a valuable tool for advancing research on this organism.

Abstract Objectives To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. Methods Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). Results The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p 0.05). Conclusions rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. Critical relevance statement The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. Key Points Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI. Graphical Abstract

Abstract The development of dietary fibers as safe and effective food additives or nutrients for preventing and alleviating inflammatory bowel disease (IBD) is increasingly important. β‐glucans, renowned prebiotics, have shown promise in alleviating IBD symptoms by modulating gut flora diversity and repairing the intestinal barrier. Auricularia auricula‐judae, an edible fungus, contains a β‐glucan with a triple‐helical structure polysaccharide from black fungus Auricularia auricula‐judae (BFP), which exhibits unique sol–gel properties. This study revealed that BFP forms weak gels or sols at increasing concentrations, enhancing swallow ability and extending intestinal transit time, beneficial for patients with dysphagia requiring targeted intestinal administration. The impact of BFP on dextran sulfate sodium (DSS)‐induced ulcerative colitis was examined, showing that BFP sols maintain intestinal barrier integrity by up‐regulating MUC2, ZO‐1, Occludin, and Claudin expressions and reducing inflammatory factors. Furthermore, BFP sols augmented probiotics abundance, decreased harmful bacteria, and restored Bacteroidetes/Firmicutes balance. These findings suggest BFP sols’ potential as functional food or alternative IBD treatment.

Identifying the stability and sensitivity of land ecosystems to climate change is vital for exploring nature-based solutions. However, the underlying mechanisms governing ecosystem stability and sensitivity, especially in regions with overlapping ecological projects, remain unclear. based on Mann-Kendall, stability analysis method, and multiple regression method, this study quantified the stability and sensitivity of gross primary productivity (GPP) to climate variables [temperature, vapor pressure deficit (VPD), soil moisture, and radiation] in China from 1982 to 2019. Our findings revealed the following: (1) GPP demonstrated an increased trend with lower stability in Eastern regions, whereas a decreasing trend with higher stability was observed in Western and Southwest China. Notably, the stability of GPP was highest (74.58%) in areas with five overlapping ecological projects: Grain to Green, Natural Forest Resource Protection Project, Three-River Ecological Conservation and Restoration Project, Return Grazing to Grassland Project, and Three-North Shelter Forestation Project. (2) In regions with minimal or no overlapping ecological projects, temperature and radiation jointly dominated GPP variations. In contrast, water-related factors (VPD and soil moisture) significantly affected GPP in areas with multiple overlapping ecological projects. (3) In the southwestern and northeastern regions, GPP exhibited the highest sensitivity to climate change, whereas, in the eastern coastal areas and Tibet, GPP showed low sensitivity to climate change. In the Loess Plateau, where five ecological projects overlap extensively, carbon sinks primarily demonstrate a monotonic increasing trend, high stability, and low sensitivity to climate change. This study aimed to assess the stability of the land ecosystems and delineate their sensitivity to climate changes, thereby laying the groundwork for understanding ecosystem resilience.

ObjectiveAlthough guidelines support the efficacy of Modified Qing’ E Formula (MQEF) in treating postmenopausal osteoporosis (PMOP), its underlying mechanisms remain incompletely understood. This retrospective investigation aims to elucidate MQEF’s impact on serum exosomal miRNA expression in postmenopausal osteoporosis patients and to explore potential therapeutic mechanisms.MethodsFollowing ethical approval and registration, postmenopausal osteoporosis patients aged 50–85 years, meeting the diagnostic criteria were randomly selected and received MQEF decoction supplementary therapy. Serum samples were collected pre- and post-treatment, followed by isolation and sequencing of exosomal miRNAs. Differential miRNAs in serum exosomes were identified, and bioinformatics analysis was conducted to discern the principal exosomal miRNAs involved in MQEF’s effects on PMOP and the associated signaling pathways.ResultsEighteen clinical blood samples were collected. A total of 282,185 target genes were detected across the three groups. 306 miRNAs exhibited altered expression in serum exosomes of PMOP patients, while MQEF intervention resulted in changes in 328 miRNAs. GO enrichment analysis revealed the immune and endocrine systems was pertained. KEGG enrichment analysis indicated associations between PMOP occurrence and MQEF treatment with cytokine interactions, oxidative phosphorylation, and the renin-angiotensin system. Intersectional analysis identified 17 miRNAs, including 2 consistent trends. miR-3188 as a potentially pivotal miRNA implicated in both PMOP occurrence and MQEF treatment.ConclusionThis study constitutes the first randomized, retrospective clinical exploration confirming that MQEF demonstrates regulatory influence over exosomal miRNA expression in PMOP patients’ serum, its impact likely involves modulation of the immune and endocrine systems, as well as the renin-angiotensin system.

BackgroundUnexplained recurrent pregnancy loss (URPL) is a clinical dilemma in reproductive fields. Its diagnosis is mainly exclusionary after extensive clinical examination, and some of the patients may still face the risk of miscarriage.MethodsWe analyzed follicular fluid (FF) from in vitro fertilization (IVF) in eight patients with URPL without endocrine abnormalities or verifiable causes of abortion and eight secondary infertility controls with no history of pregnancy loss who had experienced at least one normal pregnancy and delivery by direct data-independent acquisition (dDIA) quantitative proteomics to identify differentially expressed proteins (DEPs). In this study, bioinformatics analysis was performed using online software including g:profiler, String, and ToppGene. Cytoscape was used to construct the protein–protein interaction (PPI) network, and ELISA was used for validation.ResultsGene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEPs are involved in the biological processes (BP) of complement and coagulation cascades. Apolipoproteins (APOs) are key proteins in the PPI network. ELISA confirmed that APOB was low-expressed in both the FF and peripheral blood of URPL patients.ConclusionDysregulation of the immune network intersecting coagulation and inflammatory response is an essential feature of URPL, and this disequilibrium exists as early as the oogenesis stage. Therefore, earlier intervention is necessary to prevent the development of URPL. Moreover, aberrant lipoprotein regulation appears to be a key factor contributing to URPL. The mechanism by which these factors are involved in the complement and coagulation cascade pathways remains to be further investigated, which also provides new candidate targets for URPL treatment.

Abstract Porcine epidemic diarrhoea virus (PEDV) infects pigs of all ages by invading small intestine, causing acute diarrhoea, vomiting, and dehydration with high morbidity and mortality among newborn piglets. However, current PEDV vaccines are not effective to protect the pigs from field epidemic strains because of poor mucosal immune response and strain variation. Therefore, it is indispensable to develop a novel oral vaccine based on epidemic strains. Bacillus subtilis spores are attractive delivery vehicles for oral vaccination on account of the safety, high stability, and low cost. In this study, a chimeric gene CotC‐Linker‐COE (CLE), comprising of the B. subtilis spore coat gene cotC fused to the core neutralizing epitope CO‐26 K equivalent (COE) of the epidemic strain PEDV‐AJ1102 spike protein gene, was constructed. Then recombinant B. subtilis displaying the CLE on the spore surface was developed by homologous recombination. Mice were immunized by oral route with B. subtilis 168‐CLE, B. subtilis 168, or phosphate‐buffered saline (PBS) as control. Results showed that the IgG antibodies and cytokine (IL‐4, IFN‐γ) levels in the B. subtilis 168‐CLE group were significantly higher than the control groups. This study demonstrates that B. subtilis 168‐CLE can generate specific systemic immune and mucosal immune responses and is a potential vaccine candidate against PEDV infection.

Recent studies have emphasized that there is a strong link between the gut microbiome and the brain that affects social behavior and personality in animals. However, the interface between personality and the gut microbiome in wild primates remains poorly understood. Here, we used high-throughput sequencing and ethological methods in primate behavioral ecology to investigate the relationship between gut microbiome and personality in Tibetan macaques (Macaca thibetana). The behavioral assessment results indicated three personality dimensions including socialization, shyness, and anxiety. There was significant variation in alpha diversity only for shyness, with a significantly lower alpha diversity indices (including Shannon, Chao1, and PD) for bold individuals than for shy individuals. Using regression models to control for possible confounding factors, we found that the relative abundance of three genera, Akkermansia, Dialister, and Asteroleplasma, was significantly and positively correlated with the sociability scores in the macaques. In addition, Oscillospiraceae exhibited a positive correlation with scores for Shy Dimension. Furthermore, we found that the predicted functional genes for propionate and pyruvate, porphyrin and chlorophyll metabolic pathways related to animal behavior, were significant enriched in shyness group. We propose that the gut microbiome may play an important role in the formation of personality of Tibetan macaques.

BackgroundThe relationship between allergic diseases and the adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a subject of controversy. This study aimed to investigate the association between allergic diseases and the incidence and severity of symptoms in SARS-CoV-2 infection.MethodsClinical data of individuals, including children and their parents, infected with SARS-CoV-2 from December 2022 to January 2023 in China were retrospectively analyzed. The data were collected through questionnaires. Statistical analysis, including chi-squared tests, nonparametric analysis, one-way ANOVA, and logistic regression analysis, was used to examine the relationship between allergic diseases, prior medication, and the symptoms of SARS-CoV-2 infection.ResultsThere were 3,517 adults and 3,372 children with SARS-CoV-2 infection included in the study. Fever was found to occur at similar rates in children (86.5%) and adults (86.8%). However, other symptoms related to respiratory issues (such as cough and sore throat), neurological symptoms (headache, loss of smell, and loss of taste), and systemic symptoms (muscle soreness and weakness) were observed more frequently in adults (P < 0.001). Additionally, adults exhibited higher overall symptom scores, indicating greater severity. Allergic diseases were found to be associated with the incidence of certain SARS-CoV-2 infection symptoms in both children and adults. Specifically, children with allergic rhinitis (AR) were observed to be more susceptible to upper respiratory symptoms (OR: 1.320, 95% CI: 1.081-1.611, P = 0.006), while asthma patients were found to be more susceptible to severe respiratory symptoms (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). Similar patterns were identified in adults. Furthermore, AR was also suggested to be a risk factor for symptom severity in both children (OR: 1.704, 95% CI: 1.314-2.209, P < 0.001) and adults (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). However, prior medication for allergic diseases did not exhibit a preventive effect on SARS-CoV-2 infection symptoms.ConclusionsBoth children and adults with allergic diseases were found to be more prone to experiencing symptoms of SARS-CoV-2 infection, and these symptoms tended to be more severe.

ABSTRACT Glaesserella parasuis, a common inhabitant of the upper respiratory tract of pigs, is the etiological agent of Glässer’s disease, which is characterized by fibrinous polyserositis, polyarthritis, and meningitis. Decreased production of capsular polysaccharide (CPS) promotes bacterial adhesion and uptake, whereas maximal expression of CPS is essential to evade the host immune response. For bacterial survival under highly variable host conditions, a coordinated regulation of CPS expression is necessary. In the present study, we investigated how epinephrine (Epi) affects the CPS production, biofilm formation, and adhesion ability of G. parasuis, as well as the specific mechanism of G. parasuis changes in response to Epi. The results demonstrated that Epi stimulation dramatically inhibited CPS expression, and both the action of Epi and the deletion of CPS biosynthesis gene capD had detrimental impacts on biofilm formation, and had the enhanced ability for cell adhesion. QseBC two-component system is a typical adrenaline-sensing system in bacteria. In the present study, by quantitative real-time PCR, Western blot, and electrophoretic mobility shift assay, we discovered that in the presence of Epi, G. parasuis negatively regulated capD expression via the interaction of QseB with the promoter of capD, thereby affecting the synthesis of CPS. In conclusion, we explored the impact of Epi on CPS synthesis and defined its regulatory mechanism in G. parasuis for the first time, which provides an important theoretical basis for understanding the pathogenic mechanism of G. parasuis. IMPORTANCE The key bacterial pathogen Glaesserella parasuis, which can cause Glässer’s disease, has caused significant financial losses to the swine industry worldwide. Capsular polysaccharide (CPS) is an important virulence factor for bacteria, providing the ability to avoid recognition and killing by the host immune system. Exploring the alteration of CPS synthesis in G. parasuis in response to epinephrine stimulation can lay the groundwork for revealing the pathogenic mechanism of G. parasuis as well as providing ideas for Glässer’s disease control.

ABSTRACTGlaesserella parasuis is an early colonizer of the swine upper respiratory tract and can break through the respiratory barrier for further invasion. However, the mechanisms underlying G. parasuis increases epithelial barrier permeability remain unclear. This study demonstrates that G. parasuis cytolethal distending toxin (CDT) induces p53-dependent apoptosis in new-born piglet tracheal (NPTr) cells. Moreover, we report for the first time that leucine-rich repeat-containing protein 8A (LRRC8A), an essential subunit of the volume-regulated anion channel (VRAC), involves in apoptosis of NPTr cells mediated by G. parasuis CDT. Pharmacological inhibition of VRAC with either PPQ-102 or NS3728 largely attenuated CDT-induced apoptosis in NPTr cells. Additionally, experiments with cells knocked down for LRRC8A using small interfering ribonucleic acid (siRNA) or knocked out LRRC8A using CRISPR/Cas9 technology showed a significant reduction in CDT-induced apoptosis. Conversely, re-expression of Sus scrofa LRRC8A in LRRC8A–/– NPTr cells efficiently complemented the CDT-induced apoptosis. In summary, these findings suggest that LRRC8A is pivotal for G. parasuis CDT-induced apoptosis, providing novel insights into the mechanism of apoptosis caused by CDT.

How have plants addressed the trade-off between carbon gain and water loss in this warming world? Ecosystem water-use efficiency (WUE), defined as the ratio of gross primary productivity (GPP) to evapotranspiration (ET), is a key indicator of the carbon–water relationship. WUE is expected to change due to climate change, yet the extent to which GPP or ET affects WUE changes remains unclear. Moreover, the potential time-varying variations in the WUE responses to recent warming have been overlooked. In this study, we assessed the relative contributions of GPP and ET to WUE using variance decomposition and investigated trends in temperature controls on WUE using moving windows and partial correlation analysis. Our results include: (1) the national multi-year average WUE in China increased significantly at a rate of 0.0174 gC·kg-1H2O·a-1, with 86.88% of the study area exhibiting increased trends. Forest ecosystems, except for ENF, had relatively higher WUE, and the highest value was observed in the deciduous broad-leaf forest (3.77 gC·kg-1H2O), while grassland ecosystems had the lowest WUE of only 1.05 gC·kg-1H2O. (2) GPP, rather than ET, primary drove WUE variations in most areas, except in Northeast China and Southwest China. GPP always contributed more to WUE than ET in each land cover type. In forests, ET contributed more to WUE than in other land cover types. (3) WUE exhibited significantly positive correlations with temperature and radiation, with a positive correlation with temperature in 63.73% (14.83% significant in level of p

A clearer understanding of the stability of water use efficiency (WUE) and its driving factors contributes to improving water use efficiency and strengthening water resource management. However, the stability of WUE is unclear. Based on the EEMD method, this study analyses the spatial variations and mechanisms for the stability of WUE in China, especially in the National Forest Protection Project (NFPP) areas. It is found that the stable WUE was dominated by non-significant trends and increasing trends in China, accounting for 33.59% and 34.19%, respectively. The non-significant trend of stable WUE was mainly located in the Three-North shelterbelt program area, and the increasing trend of stable WUE was in Huaihe and Taihu, Taihang Mountains, and Pearl River shelterbelt program areas. Precipitation and soil moisture promoted the stable WUE in these project areas. The unstable WUE was dominated by positive reversals or negative reversals of WUE trends. The positive reversals of unstable WUE were mainly located in the Yellow River shelterbelt program areas, which was promoted by temperature and radiation, while the negative reversals of unstable WUE were mainly distributed in the Yangtze River and Liaohe shelterbelt program areas, which were mainly induced by saturation water vapor pressure difference (VPD). Our results highlight that some ecological restoration programs need to be improved to cope with the negative climate impact on the stability of WUE.

Abstract Gut microbiome is critical to the health of mammals. Many previous studies have revealed the gut bacterial microbiomes of mother and infant changed significantly during the weaning period. However, little is known concerning the gut mycobiome of wild primates. Here, we examined the variations on gut mycobiome between weaning and post‐weaning for both mother and infant in wild‐living Tibetan macaques (Macaca thibetana). Our results showed that the gut mycobiomes of mother and infant were dominated by two phyla Ascomycota and Basidiomycota. For both mother and infant, the ASV richness of gut mycobiome remained relatively steady from weaning to post‐weaning periods, while the Shannon indexes increased significant in weaning compared to post‐weaning periods. However, no significant difference between mother and infant ASV richness and Shannon indexes during weaning and post‐weaning periods respectively. Compared to mothers, we found that much more known taxa of gut fungi were enriched in weaning or post‐weaning periods of infants. In particular, we found that the dominant genus Aspergillus was enriched in infants during weaning period. Furthermore, we found that the relative abundance of plant pathogens were significantly higher in the post‐weaning period than in the weaning period for infants. Our results indicated that weaning events could affect the gut mycobiome significantly for both mothers and infant in Tibetan macaques, which had a stronger effect on the gut mycobiome of infant monkeys than on their mothers.

ABSTRACT: Salmonella is an important zoonotic pathogen that not only endangers food safety and human health, but also causes considerable economic losses to the poultry industry. Therefore, it is essential to establish a rapid, sensitive, and specific diagnostic method for the early detection of Salmonella infection in poultry. In this study, we developed a novel enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Salmonella antibodies using a recombinant SifA protein. Amino acid sequence comparison revealed that SifA is a relatively conserved secretory protein across Salmonella serotypes. Therefore, we hypothesized that SifA can serve as a detection antigen for diagnostic testing. The SifA protein was expressed in Escherichia coli and used as a coating antigen to establish an SifA-ELISA. Control sera from specific-pathogen-free (SPF) chickens infected with Salmonella or several other non-Salmonella pathogens were then tested using the SifA-ELISA. Specificity testing demonstrated that the SifA-ELISA could detect antibodies against 3 different serotypes of Salmonella, whereas antibodies against other non-Salmonella pathogens could not be detected. Compared to the SifA-ELISA, the Salmonella plate agglutination test (PAT) failed to detect antibodies in serum samples from chickens infected with Salmonella Typhimurium. This result suggests that our SifA-ELISA may be better than PAT at detecting Salmonella infection. Comparing clinical sera, we observed a similar rate of Salmonella positivity between SifA-ELISA and PAT (92.6%). In addition, anti-SifA antibodies were continuously detected during Salmonella infection of SPF chickens, demonstrating that SifA-ELISA could consistently detect high levels of antibodies for at least 8 wk. Furthermore, the intra-assay and interassay coefficients of variation (CV) of the SifA-ELISA were below 10%, which is considered acceptable. In summary, the SifA-ELISA established here is a promising and reliable method for detection of anti-Salmonella antibodies in poultry and may contribute to the early diagnosis of Salmonella infection.

Central Asia is one of the most sensitive regions to climate changes in the world and the grassland degradation of this region has attracted considerable concern. Quantifying the driving force of grassland degradation is important for understanding the effects of climate variation and human activities on grassland. In this study, net primary productivity (NPP) was selected as an indicator to quantitatively evaluate the relative role of climate variation and human activities in Central Asia from 2000 to 2020. This study used the global NPP product MOD17A3 as actual NPP and estimated the potential NPP using the Thornthwaite memorial model. The potential NPP and the difference between the potential NPP and actual NPP were used to represent the influence of climate variation and human activities. The grassland degradation or restoration can be demonstrated by the slope of actual NPP (SA). A positive slope value (SA) suggested that restoration occurs, whereas a negative slope value suggested that degradation occurred. The results showed that 23.08% of the total grassland area experienced grassland degradation, whereas 2.51% of the whole grassland underwent grassland restoration. Furthermore, 53.8% of the degraded grassland areas were influenced by climate variation, and 14.5% were caused by human activities. By contrast, the relative roles of climate variation and human activities in grassland restoration were 25% and 47.9%, respectively. The NPP variation also could be calculated by assessing the effects of these factors and the results showed that 55.7% of the NPP decrease was caused by climate variation, whereas 9.6% was a result of human activities. On the contrary, climate variation and human activities resulted in 19.8% and 37.3% of grassland restoration, respectively. Therefore, climate variation was the dominant factor of grassland degradation, and human activities were the main driver of grassland restoration in Central Asia.

Southwest China (SWC) holds the distinction of being the world’s largest rock desertification area. Nevertheless, the impacts of climate change and ecological restoration projects on the carbon sinks in the karst area of Southwest China have not been systematically evaluated. In this study, we calculated carbon sinks by utilizing the Carnegie–Ames–Stanford Approach (CASA) model, and the actual measurements, including the net primary productivity (NPP) data and soil respiration (Rs,) were calculated to obtain carbon sink data. Our findings suggest that the carbon sinks in the karst areas are displaying increasing trends or positive reversals, accounting for 58.47% of the area, which is larger than the overall average of 45.08% for Southwest China. This suggests that the karst areas have a greater carbon sequestration potential. However, approximately 10.42% of carbon sinks experience negative reversals. The regions with increasing and positive reversals are primarily located in the western parts of Guizhou and Guangxi, while negative reversals are observed in the eastern parts of Chongqing, Guangxi, and Guizhou. Ecological restoration projects are the main driving factors for the carbon sinks with increasing trends. Increased humidity and ecological restoration management are the main reasons for the positive reversals of carbon sinks. However, warming and drought shift the carbon sinks from increasing to decreasing in Chongqing, east of Guangxi and Guizhou. The findings of this study highlight the significant role of ecological restoration projects and reexamine the impact of climate change on carbon sequestration.

Podophyllum hexandrum Royle is an alpine medicinal plant of considerable importance, and its seed dormancy severely inhibits population renewal. Although cold stratification can break dormancy to a certain extent, the migration and accumulation of phytochemicals and inorganic elements in the seeds during dormancy release and their functions remain unclear. Changes in phytochemicals and inorganic elements in different seed parts were analyzed during dormancy. The key differential phytochemicals and inorganic elements were screened and their association with dormancy release and their roles in dormancy release were explored. The results showed that dormancy release may have occurred following the decrease in palmitic acid and linoleic acid content in the seeds and the increase in 2,3-dihydro-3,5-dihydro-6-methyl-4 (h)-pyran-4-one content in the endosperm. Meanwhile, 6-propyltridecane and hexadecane in the seed coat may enhance the water permeability of seeds to speed up germination. Mg may migrate from the seed coat to the endosperm and seed embryos, whereas Co may migrate from the seed embryo to the seed coat. Ca, Mn, Mg, and Co are involved in various physiological metabolic processes, which may facilitate the dormancy release of P. hexandrum seeds. These findings have enhanced our understanding of the mechanisms of dormancy release in P. hexandrum seeds and can serve as a reference for the development of more effective dormancy-breaking techniques for the conservation of this endangered medicinal plant.

Daidzin, 4′, 7-dihydroxyisoflavone is an isoflavonic phytoestrogen present in leguminous plants. Traditional Chinese medicine utilizes daidzin to treat various diseases such diarrhea, fever, hepatitis, cardiac problems etc. In current study we examined the anticancer activity of daidzin against human cervical cancer in vitro. HeLa, human cervical cancer cell line was purchased from ATCC and the cells were cultured with DMEM medium. The cytotoxic effect of daidzin against HeLa cell line was analyzed with MTT assay. The IC-50 value was obtained at 20 µM hence the cells were treated with 20 µM of daidzin for further analysis. ROS generation was assessed with DCFH-DA staining and the induction of apoptosis was examined with Rhoadmine-123 staining. Acridine orange and ethidium bromide staining was done to examine the apoptotic and viable cells. Further the matrigel cell adhesion assay was done to analyze the inhibitory property of daidzin against cancer cell adhesion. Apoptotic induction of daidzin was examined by estimating the levels of Caspase 8 & 9 using ELISA technique. Inflammatory and cell proliferation signaling proteins were analyzed with qPCR analysis to confirm the anticancer activity of daidzin against human cervical cancer HeLa cell line. Daidzin significantly generated ROS and altered the mitochondrial membrane permeability in HeLa cell line. The results of AO/EtBr staining prove daidzin induced apoptosis in HeLa cell line and it also inhibited the cell adhesion property of HeLa which is reported in our matrigel cell adhesion assay. It also increased the caspases 8 & 9 which are key regulators of apoptosis. Daidzin significantly decreased the expression of inflammatory gene and cell proliferating signaling molecule. To, conclude our results confirm daidzin effectively decreased inflammation and induced apoptosis in human cervical cancer HeLa cell line.

BackgroundGlaesserella parasuis causes Glässer’s disease, which is associated with severe polyarthritis, fibrinous polyserositis and meningitis, and leads to significant economic losses to the swine industry worldwide. IgA is one of the most important humoral immune factors present on mucosal surfaces, and it plays a crucial role in neutralizing and removing pathogens. G. parasuis is able to colonize the mucosal membrane of respiratory tract without being eliminated. Nevertheless, the immune evasion mechanism of G. parasuis in thwarting IgA remains unclear.AimsThe object of this study is to characterize the IgA degradation activity of Mac-1-containing autotransporter EspP1 and EspP2 from G. parasuis.MethodsThe swine IgA was purified and incubated with EspP1 and EspP2 respectively. Western blotting was used to detect the cleavage of swine IgA. Generation of EspP1 and EspP2 mutant protein were used to explore the putative active sites of EspPs. LC-MS/MS based N/C-terminal sequencing was performed to measure the cleavage sites in swine IgA.ResultOur results show that G. parasuis EspP1 and EspP2 cleave swine IgA in a dose- and time- dependent manner. G. parasuis lose the IgA protease activity after simultaneously delete espP1 and espP2 indicating that EspP1 and EspP2 are the only two IgA proteases in G. parasuis. The IgA protease activity of EspP1 and EspP2 is affected by the putative active sites which contain Cys47, His172 and Asp194/195. Swine IgA is cleaved within Cα1 and Cα3 domains upon incubation with EspPs. Moreover, EspPs can degrade neither IgG nor IgM while G. parasuis possess the ability to degrade IgM unexpectedly. It suggests that G. parasuis can secrete other proteases to cleave IgM which have never been reported.ConclusionWe report for the first time that both EspP1 and EspP2 are novel IgA-specific proteases and cleave swine IgA within the Cα1 and Cα3 domains. These findings provide a theoretical basis for the EspPs-induced immune evasion.

Documenting the effects of anthropogenic activities on the gut microbiome of wild animals is important to their conservation practices. Captivity and ecotourism are generally considered two common anthropogenic disturbances on the health of nonhuman primates. Here, we examined the divergences of gut microbiome in different environments of Tibetan macaques. Our results showed that there were no significant differences in the alpha diversity, predominant families and genera of gut microbiomes between wild and tourist groups. However, these indexes decreased significantly in the captive individuals. In addition, the significant differences of beta diversity and community compositions between wild and tourism groups also were detected. In particular, higher potential pathogenic and predicted KEGG pathway of drug resistance (antimicrobial) were detected in the gut microbiome of individuals in captive environment. Our results indicated that living in the wild are beneficial to maintaining gut microbial diversity of Tibetan macaques, while captivity environment is harmful to the health of this macaque. Exploring ways to restore the native gut microbiome and its diversity of captive individual should pay more attention to in the future studies.

ObjectiveTo explore whether the modified Qing’ e Pills (MQEP) exerts anti-osteoporotic effects and prevents bone loss by enhancing angiogenesis.MethodsNetwork pharmacology was used to assess whether MQEP has a pro-angiogenic capacity and to predict its potential targets. Human umbilical vein endothelial cells were treated with glucocorticoids and MQEP to assess cell viability. The expression of angiotensin II type 1 receptor, angiotensin II type 2 receptor, and angiotensin converting enzyme, which are associated with the activation of the renin-angiotensin-aldosterone system, and the expression of vascular endothelial growth factor and hypoxia-inducible factor 1 alpha, which are associated with the formation of type H blood vessels, were examined by western blot and RT-qPCR. Thereafter, the glucocorticoid-induced osteoporosis model was established and intervened with MQEP. Femur scanning was performed with micro-computed tomography; trabecular spacing, trabecular thickness, and trabecular number were observed and calculated; the expression of nuclear factor-kappa B ligand and osteoprotegerin was detected by ELISA, and the ratio was calculated to evaluate the degree of bone resorption. Finally, type H blood vessels that were highly coupled to osteogenic cells were identified by immunohistochemistry staining and flow cytometry.ResultsThis is the first study to reveal and confirm that MQEP could prevent bone loss in glucocorticoid-induced osteoporosis by promoting the expression of hypoxia-inducible factor 1 alpha and vascular endothelial growth factor, which are highly associated with type H blood vessel formation. In vitro experiments confirmed that MQEP could effectively promote the proliferation of vascular endothelial cells and alleviate glucocorticoids-induced activation of the renin-angiotensin-aldosterone system, thereby reducing vascular injury.ConclusionMQEP exerts anti-osteoporosis effects and prevents bone loss by alleviating vascular injury caused by renin-angiotensin-aldosterone system activation and promoting type H blood vessel formation.

ObjectiveTo investigate the differential expression of exosomal miRNAs in the bone marrow tissue of Modified Qing’ E Formula (MQEF) on steroid-induced ischemic necrosis of the femoral head (INFH) model.MethodsSteroid hormones were used to establish the INFH model and treated with MQEF. After successful modeling, femoral tissue exosomes were isolated for miRNA sequencing to obtain femoral tissue exosomal differential miRNAs. By GO analysis and KEGG analysis of the differential genes in both groups, the major exosomal miRNAs of MQEF exerting anti-INFH as well as the major signaling pathways were identified. Next, a quantitative metabolomic validation of MQEF with broad targeting was performed to obtain the main active components of MQEF and to perform biological analysis and signaling pathway prediction of the active components by network pharmacology. Finally, the sequencing results were validated by using RT-qPCR. The results of miRNA sequencing were verified by double examination of network pharmacology and RT-qPCR, and the exosomal miRNAs regulated by the anti-INFH effect of MQEF and the specific signaling pathway of the effect were clarified.ResultsA total of 65,389 target genes were predicted in the exosomes of two groups of mice, and 18 significant differentially expressed miRNAs were obtained, of which 14 were up-regulated and 4 down-regulated. GO enrichment analysis showed that these predicted target genes were enriched in 12371 biological processes, 1727 cell components, and 4112 molecular functions. KEGG analysis showed that the predicted miRNA target genes were annotated to 342 signal pathways, in which the highly enriched pathways closely related to bone metabolism were PI3K-Akt signal pathway, MAPK signal pathway, and Wnt signal pathway. The most significantly up-regulated miRNAs were miR-185-3p and miR-1b-5p and the most significantly down-regulated miRNAs were miR-129b-5p and miR-223-5p, of which the targeted genes were closely related to the PI3K-Akt signal pathway. MQEF aqueous decoction extract targeted metabolomics quantitatively combined with network pharmacology predicted targets also closely related to PI3K-Akt signaling pathway. Real-time quantitative PCR validation showed that miR-185-3p was up-regulated 7.2-fold and miR-129b-5p was down-regulated 2.2-fold in the treatment group, and the difference was significant (P < 0.05).ConclusionsMQEF can regulate exosomal miRNA expression in steroid-induced INFH models, miR-185-3p or miR-129b-5p/PI3K-Akt signal axis may be part of the mechanism of MQEF against steroid-induced INFH.

Glaesserella parasuis is well-known for causing Glässer’s disease, which costs the worldwide swine industry millions of dollars each year. It has been reported the symptom of pleural thickening during Glässer’s disease but this symptom has received little attention. And there is no research on the elements which promote pleural thickening. In this study, pleural thickening was discovered to be associated with increased collagen fibers and elastic fibers. Furthermore, collagen-I and elastin were found to be up-regulated and concentrated in the pleura at the mRNA and protein levels following infection. To summarize, our findings add to the theoretical understanding of Glässer’s disease and provide strong support for further research into the pathogenic mechanism of Glaesserella parasuis and the program’s target treatment.

In this study, apple pectin (AP) and tomato pectin (TP) were demonstrated to be a high-ester (74.8%) polysaccharide with the weight-average molecular weight (Mw) of ∼ 243 kDa and a low-ester (45.9%) polysaccharide with the Mw of ∼ 19 kDa, respectively. The semi-rigid chain conformations of pectic polysaccharides in NaNO3 aqueous solution were deduced according to the Smidsrød “B values” of AP (0.025) and TP (0.029), while AP and TP exhibited higher stiffness in water due to the electric repulsion of carboxyl groups, which was visually observed by AFM images. Under steady shear, the shear-thickening behaviors of AP and TP in NaNO3 aqueous solutions were observed in the shear rate range of

Alkyl organophosphate flame retardants (OPFRs), tri-n-butyl phosphate (TnBP) and tris(2-butoxyethyl) phosphate (TBOEP), are ubiquitously detected in indoor and outdoor environments and their inhalation may result in lung damage. This study examined pulmonary toxicity after exposure to TnBP or TBOEP and investigated aggravation of inflammation and immunoreaction by TnBP in an ovalbumin (OVA)-induced mice model. Transcriptomics were used to further reveal the underlying mechanism. Exposure to TnBP or TBOEP resulted in pathological damage, including edema and thickened alveolar septum. In comparison with the control, enhanced levels of superoxide dismutase (SOD) (p

BackgroundCytolethal distending toxin (CDT) is a critical virulence factor of Campylobacter jejuni, and it induces cell death and regulates inflammation response in human epithelial cells. Pyroptosis is an inflammatory form of programmed cell death (PCD), but whether it is involved in CDT-mediated cytotoxicity remains elusive.AimsThis study explores the role and mechanism of pyroptosis in CDT-mediated cytotoxicity.MethodsHCT116 and FHC cell lines were treated with CDT. Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability. Western blotting was used to measure the expression of related proteins in the pathway, and cell morphology observation, annexin V/propidium iodide (PI) staining and lactate dehydrogenase (LDH) release assay were performed to evaluate the occurrence of pyroptosis.ResultOur results show that C. jejuni CDT effectively induces pyroptosis in a dose- and time- dependent manner in human colonic epithelial cells owing to its DNase activity. Specific pyroptotic features including large bubbles emerging from plasma membrane and LDH release were observed upon CDT treatment. Moreover, CDT-induced pyroptosis involves the caspase-9/caspase-3 axis, which is followed by gasdermin E (GSDME) cleavage rather than gasdermin D (GSDMD). N-acetyl cysteine (NAC), a reactive oxygen species (ROS) inhibitor, attenuates the activation of caspase-9/3, the cleavage of GSDME and pyroptotic characteristic, therefore demonstrating ROS initiates pyroptotic signaling.ConclusionsWe first clarify a molecular mechanism that CDT induces pyroptosis via ROS/caspase-9/caspase-3/GSDME signaling. These findings provide a new insight on understanding of CDT-induced pathogenesis at the molecular level.

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive neuronal cell loss. Recently, dysregulation of intracellular Ca2+ homeostasis has been suggested as a common proximal cause of neural dysfunction in AD. Here, we investigated (1) the pathogenic role of destabilization of ryanodine receptor (RyR2) in endoplasmic reticulum (ER) upon development of AD phenotypes in App NL-G-F mice, which harbor three familial AD mutations (Swedish, Beyreuther/Iberian, and Arctic), and (2) the therapeutic effect of enhanced calmodulin (CaM) binding to RyR2. In the neuronal cells from App NL-G-F mice, CaM dissociation from RyR2 was associated with AD-related phenotypes, i.e. Aβ accumulation, TAU phosphorylation, ER stress, neuronal cell loss, and cognitive dysfunction. Surprisingly, either genetic (by V3599K substitution in RyR2) or pharmacological (by dantrolene) enhancement of CaM binding to RyR2 reversed almost completely the aforementioned AD-related phenotypes, except for Aβ accumulation. Thus, destabilization of RyR2 due to CaM dissociation is most likely an early and fundamental pathogenic mechanism involved in the development of AD. The discovery that neuronal cell loss can be fully prevented simply by stabilizing RyR2 sheds new light on the treatment of AD.

Backgrounds: Advanced schistosomiasis is the late stage of schistosomiasis, seriously jeopardizing the quality of life or lifetime of infected people. This study aimed to develop a nomogram for predicting mortality of patients with advanced schistosomiasis japonica, taking Dongzhi County of China as a case study. Method: Data of patients with advanced schistosomiasis japonica were collected from Dongzhi Schistosomiasis Hospital from January 2019 to July 2022. Data of patients were randomly divided into a training set and validation set with a ratio of 7:3. Candidate variables, including survival outcomes, demographics, clinical features, laboratory examinations, and ultrasound examinations, were analyzed and selected by LASSO logistic regression for the nomogram. The performance of the nomogram was assessed by concordance index (C-index), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The calibration of the nomogram was evaluated by the calibration plots, while clinical benefit was evaluated by decision curve and clinical impact curve analysis. Results: A total of 628 patients were included in the final analysis. Atrophy of the right liver, creatinine, ascites level III, N-terminal procollagen III peptide, and high-density lipoprotein were selected as parameters for the nomogram model. The C-index, sensitivity, specificity, PPV, and NPV of the nomogram were 0.97 (95% [CI]: [0.95–0.99]), 0.78 (95% [CI]: [0.64–0.87]), 0.97 (95% [CI]: [0.94–0.98]), 0.78 (95% [CI]: [0.64–0.87]), 0.97 (95% [CI]: [0.94–0.98]) in the training set; and 0.98 (95% [CI]: [0.94–0.99]), 0.86 (95% [CI]: [0.64–0.96]), 0.97 (95% [CI]: [0.93–0.99]), 0.79 (95% [CI]: [0.57–0.92]), 0.98 (95% [CI]: [0.94–0.99]) in the validation set, respectively. The calibration curves showed that the model fitted well between the prediction and actual observation in both the training set and validation set. The decision and the clinical impact curves showed that the nomogram had good clinical use for discriminating patients with high risk of death. Conclusions: A nomogram was developed to predict prognosis of advanced schistosomiasis. It could guide clinical staff or policy makers to formulate intervention strategies or efficiently allocate resources against advanced schistosomiasis.

Telomeres are closely associated with the development of cell aging. Shortening or erosion of telomeres will cause cell mortality, suggesting that the maintenance of telomere integrity facilitates cell anti-senescence. However, the mechanism of how to keep the telomere length remains fragmentary. Here, we found that polyadenylated telomeric noncoding RNA (TERRA) can promote the self-renewal when overexpressed in mouse embryonic stem cells (mESCs), implying that TERRA with polyadenylation is critical for mESC maintenance. Further studies revealed that TERRA with a polyadenylated tail plays an important role in the sustenance of telomere length. High-throughput sequencing and quantitative real-time PCR show that zinc finger and SCAN domain containing 4C (Zscan4c) may be a potential target of TERRA. Zscan4c is negatively regulated by TERRA and collaborates with TERRA to stabilize the telomere length of chromosomes in mESCs. Our study not only identifies TERRA as a potential novel factor of telomere length regulation and uncovers the new molecular mechanism of cell anti-aging, but also indicates that Zscan4c could be a key therapeutic target candidate for therapy in dysfunctional chromosome diseases. These data will expand our understanding of the cell fate regulatory network and will be beneficial to drug discovery and theragnostics for antiaging and anticancer therapy in the future.

Abstract Background Haemophilus parasuis is a commensal pathogen in the swine upper respiratory tract and causes Glässer’s disease. Surveillance, screening for infection, and vaccination response of H. parasuis is hindered by the lack of a rapid antibody detection method. Results In the present study, a monomeric autotransporter was identified as a novel antigen for developing an indirect ELISA. The autotransporter passenger domain (Apd) was expressed, purified, and demonstrated to be specific in ELISA and western blotting. Mouse antiserum of recombinant Apd (rApd) recognized native Apd in the 15 serotype reference strains and five non-typeable isolate stains, but showed no reaction with seven other bacterial pathogens. The rApd ELISA was optimized and validated using 67 serum samples with known background, including 27 positive sera from experimentally infected and vaccinated pigs along with 40 negative sera that had been screened with H. parasuis whole cell ELISA from clinically healthy herds. The rApd ELISA provided positive and negative percent agreements of 96.4 and 94.9%, respectively, and an AUC value of 0.961, indicating that the assay produced accurate results. Conclusion Apd was a universal antigen component among 15 serotype and non-typeable strains of H. parasuis and was also specific to this pathogen. The rApd ELISA could detect antibodies elicited by H. parasuis infection and vaccination, thereby exhibiting the potential to be applied for Glässer’s disease diagnosis, H. parasuis vaccination evaluation, and large-scale serological surveillance.

The distribution and availability of microbes in the environment has an important effect on the composition of the gut microbiome of wild vertebrates. However, our current knowledge of gut-environmental interactions is based principally on data from the host bacterial microbiome, rather than on links that establish how and where hosts acquire their gut mycobiome. This complex interaction needs to be clarified. Here, we explored the relationship between the gut fungal communities of Tibetan macaques (Macaca thibetana) and the presence of environmental (plant and soil) fungi at two study sites using the fungal internal transcribed spacer (ITS) and next generation sequencing. Our findings demonstrate that the gut, plant and soil fungal communities in their natural habitat were distinct. We found that at both study sites, the core abundant taxa and ASVs (Amplicon Sequence Variants) of Tibetan macaques’ gut mycobiome were present in environmental samples (plant, soil or both). However, the majority of these fungi were characterized by a relatively low abundance in the environment. This pattern implies that the ecology of the gut may select for diverse but rare environmental fungi. Moreover, our data indicates that the gut mycobiome of Tibetan macaques was more similar to the mycobiome of their plant diet than that present in the soil. For example, we found three abundant ASVs (Didymella rosea, Cercospora, and Cladosporium) that were present in the gut and on plants, but not in the soil. Our results highlight a relationship between the gut mycobiome of wild primates and environmental fungi, with plants diets possibly contributing more to seeding the macaque’s gut mycobiome than soil fungi.

Abstract Background Oocytes have a lot of maternal RNAs and proteins, which are used by the early embryo before zygotic genome activation. Transducin‐like enhancer of split 6 (TLE6) is a component of a subcortical maternal complex which plays a critical role in early embryonic development. Methods The patient had been diagnosed with primary infertility for 6 years and had undergone multiple failed in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Genomic DNA samples were extracted from her parents’ peripheral blood as well as hers. Whole‐exome sequencing and Sanger validation were performed to identify candidate variants. Results We identified a novel transducin‐like enhancer of split 6 (TLE6) gene mutations in the female patient with recurrent IVF/ICSI failure. The patient carried a homozygous mutation (NM_001143986.1(TLE6): c.541+1G>A) and had viable but low‐quality embryos. Her parents both had heterozygous mutations at this locus. Conclusion Our study expands the mutational and phenotypic spectrum of TLE6 and suggests the important role of TLE6 during embryonic development. Our findings have implications for the genetic diagnosis of female infertility with recurrent IVF/ICSI failure.

The rate of vegetation green-up (RVG) indicates the ability of vegetation to respond to changes in climatic conditions. Understanding long-term RVG trends can clarify the changes in how quickly the vegetation grows from dormancy to maturity with time. However, how RVG trends respond to environmental variables and variable interactions remains unknown. We examined the long-term RVG trends (1981–2018) over the northern extratropics and determined the influence of environment variables and interactions between variables on the RVG trends based on the Global Land Surface Satellite leaf area index and a multivariable regression considering interactions between variables (MRCI). Our results showed a persistent increase in RVG at 0.020% (8-day)−1 year−1 over the entire region. Except for shrublands (−0.032% (8-day)−1 year−1), RVG trends increased significantly, particularly in woody savannas (0.095% (8-day)−1 year−1) and mixed forests (0.076% (8-day)−1 year−1). The relative importance of interactive effects (RIIAE) to the RVG trends is roughly 30%. Rising CO2, enhanced vapor pressure deficit (VPD), and warming are the primary factors affecting the RVG trends, both at the pixel and the biome scales. The accelerated RVG is triggered by both rising CO2 and warming but is partially offset by increased VPD. Our findings shed light on the relative contribution of variable interactions and assessed the relationship between environmental factors and RVG trends across different biomes, hence strengthening our knowledge of vegetation spring green-up in response to global change.

Although recent studies have revealed that gut fungi may play an important functional role in animal biology and health, little is known concerning the effects of anthropogenic pressures on the gut mycobiome. Here, we examined differences of the gut mycobiome in wild and captive populations of Tibetan macaques (Macaca thibetana) targeting the fungal internal transcribed spacer (ITS) and using next generation sequencing. Our findings demonstrate that the diversity, composition, and functional guild of the Tibetan macaque gut mycobiome differ across populations living in different habitats. We found that Tibetan macaques translocated from the wild into a captive setting for a period of 1 year, were characterized by a reduction in fungal diversity and an increase in the abundance of potential gut fungal pathogens compared to wild individuals. Furthermore, we found that the relative abundance of two main fungal guilds of plant pathogens and ectomycorrhizal fungi was significantly lower in captive individuals compared to those living in the wild. Our results highlight that, in addition to bacteria, gut fungi vary significantly among individuals living in captive and wild settings. However, given limited data on the functional role that fungi play in the host’s gut, as well as the degree to which a host’s mycobiome is seeded from fungi in the soil or ingested during the consumption of plant and animal foods, controlled studies are needed to better understand the role of the local environment in seeding the mycobiome.

Bacterial lipooligosaccharide (LOS) is an important virulence-associated factor, and its sialylation largely confers its ability to mediate cell adhesion, invasion, inflammation, and immune evasion. Here, we investigated the function of the Haemophilus parasuis α-2,3-sialyltransferase gene, lsgB, which determines the terminal sialylation of LOS, by generating a lsgB deletion mutant as well as a complementation strain. Our data indicate a direct effect of lsgB on LOS sialylation and reveal important roles of lsgB in promoting the pathogenicity of H. parasuis, including adhesion to and invasion of porcine cells in vitro, bacterial load and survival in vivo, as well as a contribution to serum resistance. These observations highlight the function of lsgB in mediating LOS sialylation and more importantly its role in H. parasuis infection. These findings provide a more profound understanding of the pathogenic mechanism of this disease-causing bacterium.

In this paper, exploratory and innovative research is done on the implementation technique of artistic color virtual reality for similarity image recovery. Based on similarity images, a nonlocal natural image before the regular term is proposed to deal with the single-image blind deblurring problem. This paper designs a new artistic color virtual reality realization technology based on similarity image restoration, which exploits the low-rank property between nonlocal similarity blocks in images and combines a strong convex term to enhance the convexity of the artistic color virtual reality model. We analyze virtual reality interaction design from the perspective of art color design, sort out the concept and content of design, analyze the elements, design principles, and evaluation criteria included in virtual reality interaction art color design, and explore the conceptual principles of virtual reality interaction art color design. A full understanding of the characteristics of the medium of the virtual reality interaction can help us to better use this medium as a tool to create works that aim to bring higher quality and experiential feeling with a perceptual communication method that is closer to natural interaction. Combining the power of technology, artistic colourful thinking, and a design approach paves the way forward. The study shows that virtual reality technology can effectively improve the status quo and promote the cultivation of professional practice ability in art color design, which is conducive to the cultivation of applied design talents.

Introduction: Assessment of lymph node metastasis (LNM) is crucial for treatment decision and prognosis prediction for endometrial cancer (EC). However, the sensitivity of the routinely used magnetic resonance imaging (MRI) is low in assessing normal-sized LNM (diameter, 0–0.8 cm). We aimed to develop a predictive model based on magnetic resonance (MR) images and clinical parameters to predict LNM in normal-sized lymph nodes (LNs).Materials and Methods: A total of 200 retrospective patients were enrolled and divided into a training cohort (n = 140) and a test cohort (n = 60). All patients underwent preoperative MRI and had pathological result of LNM status. In total, 4,179 radiomic features were extracted. Four models including a clinical model, a radiomic model, and two combined models were built. Area under the receiver operating characteristic (ROC) curves (AUC) and calibration curves were used to assess these models. Subgroup analysis was performed according to LN size. All patients underwent surgical staging and had pathological results.Results: All of the four models showed predictive ability in LNM. One of the combined models, ModelCR1, consisting of radiomic features, LN size, and cancer antigen 125, showed the best discrimination ability on the training cohort [AUC, 0.892; 95% confidence interval [CI], 0.834–0.951] and test cohort (AUC, 0.883; 95% CI, 0.786–0.980). The subgroup analysis showed that this model also indicated good predictive ability in normal-sized LNs (0.3–0.8 cm group, accuracy = 0.846;

Type 2 diabetes, a long-term chronic metabolic disease, causes severe and increasing economic and health problems globally. There is growing evidence that β-glucans can function as bioactive macromolecules that help control type 2 diabetes with minimal side effects. However, conflicting conclusions about the antidiabetic activities of β-glucans have been published, potentially resulting from incomplete understanding of their precise structural characteristics. This review aims to increase clarity on the structure–function relationships of β-glucans in treating type 2 diabetes by examining detailed structural and conformational features of naturally derived β-glucans, as well as both chemical and instrumental methods used in their characterization, and their underlying anti-diabetic mechanisms. This may help to uncover additional structure and function relationships and to expand applications of β-glucans.

Increasing the level of reactive oxygen species (ROS) in cancer cells has been suggested as a viable approach to cancer therapy. Our previous study has demonstrated that mitochondria-targeted flavone-naphthalimide-polyamine conjugate 6c elevates the level of ROS in cancer cells. However, the detailed role of ROS in 6c-treated cancer cells is not clearly stated. The biological effects and in-depth mechanisms of 6c in cancer cells need to be further investigated. In this study, we confirmed that mitochondria are the main source of 6c-induced ROS, as demonstrated by an increase in 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSox fluorescence. Compound 6c-induced mitochondrial ROS caused mitochondrial dysfunction and lysosomal destabilization confirmed by absolute quantitation (iTRAQ)-based comparative proteomics. Compound 6c-induced metabolic pathway dysfunction and lysosomal destabilization was attenuated by N-acetyl-L-cysteine (NAC). iTRAQ-based comparative proteomics showed that ROS regulated the expression of 6c-mediated proteins, and treatment with 6c promoted the formation of autophagosomes depending on ROS. Compound 6c-induced DNA damage was characterized by comet assay, p53 phosphorylation, and γH2A.X, which was diminished by pretreatment with NAC. Compound 6c-induced cell death was partially reversed by 3-methyladenine (3-MA), bafilomycin (BAF) A1, and NAC, respectively. Taken together, the data obtained in our study highlighted the involvement of mitochondrial ROS in 6c-induced autophagic cell death, mitochondrial and lysosomal dysfunction, and DNA damage.

The gut microbiome is expected to adapt to the varying energetic and nutritional pressures in females of different reproductive states. Changes in the gut microbiome may lead to varying nutrient utilizing efficiency in pregnant and lactating female primates. In this study, we examined variation in the gut bacterial community composition of wild female Tibetan macaques (Macaca thibetana) across different reproductive states (cycling, pregnancy and lactation). Fecal samples (n = 25) were collected from ten adult females harvested across different reproductive states. Gut microbial community composition and potential functions were assessed using 16 S rRNA gene sequences. We found significant changes in gut bacterial taxonomic composition, structure and their potential functions in different reproductive states of our study species. In particular, the relative abundance of Proteobacteria increased significantly during pregnancy and lactation. In addition, the relative abundance of Succinivibrionaceae and Succinivibrio (Succinivibrionaceae) were overrepresented in pregnant females, whereas Bifidobacteriaceae and Bifidobacterium (Bifidobacteriaceae) were overrepresented in lactating females. Furthermore, the relative abundance of predicted functional genes of several metabolic pathways related to host’s energy and nutrition, such as metabolism of carbohydrates, cofactors and vitamins, glycans and other amino acids, were enriched in pregnancy and lactation. Our findings suggest that changes in the gut microbiome may play an important role in meeting the energetic needs of pregnant and lactating Tibetan macaques. Future studies of the “microbial reproductive ecology” of primates that incorporate food availability, reproductive seasonality, female reproductive physiology and gut inflammation are warranted.

The trend of vegetation phenology dynamics is of crucial importance for understanding vegetation growth and its responses to climate change. However, it remains unclear how the trends of vegetation phenology changed over the past decades. By analyzing phenology data including start (SOS), end (EOS) and length (LOS) of growth season with the Ensemble empirical mode decomposition (EEMD), we revealed the trend evolution of vegetation phenology in China during 1981-2016. Our study suggests that: (1) On the national scale, with EEMD method, the change rates of SOS and LOS were increasing with time, while that of EOS was decreasing. Moreover, the EEMD rates of SOS and LOS exceeded the linear rates in the early-2000s, while that of EOS dropped below the linear rate in the mid-1980s. (2) For each phenological event, the shifted trends took up a large area (~30%), which was close to the sum of all monotonic trends, but more than any monotonic trend type. The shifted trends mainly occurred in the north-eastern China, eastern Qinghai-Tibetan Plateau, eastern Sichuan Basin, North China Plain and Loess Plateau. (3) For each phenological event, the areas in the high-latitude experienced the contrary trends to the other. The amplitude and frequencies of phenology variation in the mid-latitude were stronger than those in the high-latitude and low-latitude. Meanwhile, LOS in the high-latitude was induced by SOS. (4) For each phenological event, the trend evolution varying with longitudes can be divided into eastern region (east of 121°E), central region (92°E−121°E) and western region (west of 92°E) based on the evolution of trends varying with longitudes. The east experienced a delayed SOS and a shorten LOS, which was different from the other areas. The magnitude of delayed trends in EOS and the prolonged trends in LOS were stronger from east to west as longitudes changes. The variation characteristics of LOS with longitude were mainly caused by SOS in the eastern region and by SOS and EOS together in the western and central region. (5) Each land cover types, except Needleleaf Forests, experienced the same trends. For most land cover types, the advance of SOS, delay of EOS and extension of LOS began in the 1980s, the 1990s, and the 1990s, respectively and enhanced several times. Moreover, the magnitudes of Grasslands in SOS and Evergreen Broadleaf Forest in EOS were much greater than the others, while that of croplands was the smallest in each phenological event. Our results showed that the analysis of trend evolution with nonlinear method is very important to accurately reveal the variation characteristics of phenology trends and to extract the inherent trend shifts.

Colorectal cancer (CRC) is one of the most prevalent cancers due to its frequency and high rate of mortality. Polyamine-vectorized anticancer drugs possess multiple biological properties. Of these drugs, 9F has been shown to inhibit tumor growth and the metastasis of hepatocellular carcinoma. This current study aims to investigate the effects of 9F on CRC and determine its molecular mechanisms of action. Our findings demonstrate that 9F inhibits CRC cell growth by inducing apoptosis and cell cycle arrest, and suppresses migration, invasion and angiogenesis in vitro, resulting in the inhibition of tumor growth and metastasis in vivo. Based on RNA-seq data, further bioinformatic analyses suggest that 9F exerts its anticancer activities through p53 signaling, which is responsible for the altered expression of key regulators of the cell cycle, apoptosis, the epithelial-to-mesenchymal transition (EMT), and angiogenesis. In addition, 9F is more effective than amonafide against CRC. These results show that 9F can be considered as a potential strategy for CRC treatment.

Vegetation is known to be sensitive to both climate change and anthropogenic disturbance in the karst region. However, the relationship between an abrupt change in vegetation and its driving factors is unclear at multiple timescales. Based on the non-parametric Mann-Kendall test and the ensemble empirical mode decomposition (EEMD) method, the abrupt changes in vegetation and its possible relationships with the driving factors in the karst region of southwest China during 1982−2015 are revealed at multiple timescales. The results showed that: (1) the Normalized Difference Vegetation Index (NDVI) showed an overall increasing trend and had an abrupt change in 2001. After the abrupt change, the greening trend of the NDVI in the east and the browning trend in the west, both changed from insignificant to significant. (2) After the abrupt change, at the 2.5-year time scale, the correlation between the NDVI and temperature changed from insignificantly negative to significantly negative in the west. Over the long-term trend, it changed from significantly negative to significantly positive in the east, but changed from significantly positive to significantly negative in the west. The abrupt change primarily occurred on the long-term trend. (3) After the abrupt change, 1143.32 km2 farmland was converted to forests in the east, and the forest area had significantly increased. (4) At the 2.5-year time scale, the abrupt change in the relationships between the NDVI and climate factors was primarily driven by climate change in the west, especially rising temperatures. Over the long-term trend, it was caused by ecological protection projects in the east, but by rising temperatures in the west. The integration of the abrupt change analysis and multiple timescale analysis help assess the relationship of vegetation changes with climate changes and human activities accurately and comprehensively, and deepen our understanding of the driving mechanism of vegetation changes, which will further provide scientific references for the protection of fragile ecosystems in the karst region.

Prompted by preliminary findings, this study was conducted to investigate the impact of zoledronic acid on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.96 8-week-old specific-pathogen-free C57BL/6 mice were randomly divided into 4 groups (24 per group): a sham group, an ovariectomized osteoporosis model group, an estradiol-treated group, and a zoledronic acid-treated group. Five months after surgery, the third lumbar vertebra and left femur of the animals were dissected and scanned using micro-computed tomography (micro-CT) to acquire three-dimensional imagery of their cancellous bone microstructure. The impact of ovariectomy, the effect of estradiol, and the effect of zoledronic acid intervention on cancellous bone microstructure, as well as on the expression of β-catenin, were evaluated.The estradiol-treated and the zoledronic acid-treated group exhibited a significant increase in the bone volume fraction, trabecular number, trabecular thickness, bone surface to bone volume ratio (BS/BV), and β-catenin expression, when compared with those of the control group (P

Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound 3a moderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound 3a inhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that 3a could up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound 3a is a valuable lead compound worthy of further investigation.

In 2004, 3 and 4 strains of avian influenza virus (subtype H5N1) were isolated from waterfowl and chickens, respectively, in central People’s Republic of China. Viral replication and pathogenicity were evaluated in chickens, quails, pigeons, and mice. We analyzed the sequences of the hemagglutinin and neuraminidase genes of the isolates and found broad diversity among them.