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Abstract The functionally pleiotropic ectoenzyme CD38 is a glycohydrolase widely expressed on immune and non-hematopoietic cells. By converting NAD+ to ADP-ribose and nicotinamide, CD38 governs organismal NAD+ homeostasis and the activity of NAD+-dependent cellular enzymes. CD38 has emerged as a major driver of age-related NAD+ decline underlying adverse metabolic states, frailty and reduced health span. CD38 is upregulated in systemic sclerosis (SSc), a chronic disease characterized by fibrosis in multiple organs. We sought to test the hypothesis that inhibition of the CD38 ecto-enzymatic activity using a heavy-chain monoclonal antibody Ab68 will, via augmenting organismal NAD+, prevent fibrosis in a mouse model of SSc characterized by NAD+ depletion. Here we show that treatment of mice with a non-cytotoxic heavy-chain antibody that selectively inhibits CD38 ectoenzyme resulted in NAD+ boosting that was associated with significant protection from fibrosis in multiple organs. These findings suggest that targeted inhibition of CD38 ecto-enzymatic activity could be a potential pharmacological approach for SSc fibrosis treatment.

Background Oligosaccharides have been demonstrated as promoters for enhancing plant growth across several crops by elevating their secondary metabolites. However, the exploration of employing diverse oligosaccharides for qualitative trait improvements in cauliflower largely unknown. This study was intended to uncover the unexplored potential, evaluating the stimulatory effects of three oligosaccharides on cauliflower’s curd and seed production. Methods Two experiments were initiated in the early (15 September) and mid-season (15 October). Four treatments were implemented, encompassing a control (water) alongside chitosan oligosaccharide (COS 50 mg.L–1) with a degree of polymerization (DP) 2–10, oligo galacturonic acid (OGA 50 mg.L−1) with DP 2–10 and alginate oligosaccharide (AOS 50 mg.L−1) with DP 2–7. Results Oligosaccharides accelerated plant height (4–17.6%), leaf number (17–43%), curd (5–14.55%), and seed yield (17.8–64.5%) in both early and mid-season compared to control. These enhancements were even more pronounced in the mid-season (7.6–17.6%, 21.37–43%, 7.27–14.55%, 25.89–64.5%) than in the early season. Additionally, three oligosaccharides demonstrated significant disease resistance against black rot in both seasons, outperforming the control. As a surprise, the early season experienced better growth parameters than the mid-season. However, performance patterns remained more or less consistent in both seasons under the same treatments. COS and OGA promoted plant biomass and curd yield by promoting Soil Plant Analysis Development (SPAD) value and phenol content. Meanwhile, AOS increased seed yield (56.8–64.5%) and elevated levels of chlorophyll, ascorbic acid, flavonoids, while decreasing levels of hydrogen per oxide (H2O2), malondialdehyde (MDA), half maximal inhibitory concentration (IC50), and disease index. The correlation matrix and principal component analysis (PCA) supported these relations and findings. Therefore, COS and OGA could be suggested for curd production and AOS for seed production in the early season, offering resistance to both biotic and abiotic stresses for cauliflower cultivation under field conditions.

In this study, KGMOS (DP, 2-13), derived from KGM (Konjac glucomannan), was applied to elucidate plant immunity in a Nicotiana benthamiana Phytophthora nicotianae model. Application of KGMOS (25–100 mg/L) notably inhibited P. nicotianae, resulting in reduced disease indices and a significant accumulation of defense molecules such as H2O2 and callose. Transcriptomic analysis revealed that genes shared between KGMOS-treated and control plants are involved in signaling pathways, transcription regulation, hydrogen peroxide catabolism, and oxidative stress response. This suggests that KGMOS triggers H2O2 accumulation, callose deposition, and activation of the salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) pathways after pathogen inoculation. Upregulated defense-response genes in the KGMOS group included SA-related late blight-resistant, pathogenesis-related (PR), and JA/ET-related ethylene response factor (ERF) genes. Heatmap analysis showed more upregulated defense genes (PR and NPR) related to SA in the KGMOS-treated group than in controls. RT-qPCR validation revealed significant upregulation of SA and JA/ET pathway genes in KGMOS-treated plants. Higher SA content in these plants suggests enhanced disease resistance. This study concludes that KGMOS pre-treatment induced resistance against P. nicotianae, especially at a lower concentration (25 mg/L). These findings could offer valuable insights for the future application of KGMOS in controlling plant diseases for sustainable agriculture and postharvest management.

Guanylate binding protein 5 (GBP5) is an emerging immune component that has been increasingly recognized for its involvement in autoimmune diseases, particularly inflammatory bowel disease (IBD). IBD is a complex disease involving inflammation of the gastrointestinal tract. Here, we explored the functional significance of GBP5 using Gbp5 knockout mice and wildtype mice exposed to dextran sulfate sodium (DSS) to generate chronic colitis model. We found that Gbp5 deficiency protected mice from DSS-induced chronic colitis. Transcriptome analysis of colon tissues showed reduced immune responses in Gbp5 knockout mice compared to those in corresponding wildtype mice. We further observed that after repeated DSS exposure, the gut microbiota was altered, both in wildtype mice and Gbp5 knockout mice; however, the gut microbiome health index was higher in the Gbp5 knockout mice. Notably, a probiotic murine commensal bacterium, Dubosiella, was predominantly enriched in these knockout mice. Our findings suggest that GBP5 plays an important role in promoting inflammation and dysbiosis in the intestine, the prevention of which might therefore be worth exploring in regards to IBD treatment.

BackgroundPancreatic cancer remains an extremely malignant digestive tract tumor, posing a significant global public health burden. Patients with pancreatic cancer, once metastasis occurs, lose all hope of cure, and prognosis is extremely poor. It is important to investigate liver metastasis of Pancreatic cancer in depth, not just because it is the most common form of metastasis in pancreatic cancer, but also because it is crucial for treatment planning and prognosis assessment. This study aims to delve into the mechanisms of pancreatic cancer liver metastasis, with the goal of providing crucial scientific groundwork for the development of future treatment methods and drugs.MethodsWe explored the mechanisms of pancreatic cancer liver metastasis using single-cell sequencing data (GSE155698 and GSE154778) and bulk data (GSE71729, GSE19279, TCGA-PAAD). Initially, Seurat package was employed for single-cell data processing to obtain expression matrices for primary pancreatic cancer lesions and liver metastatic lesions. Subsequently, high-dimensional weighted gene co-expression network analysis (hdWGCNA) was used to identify genes associated with liver metastasis. Machine learning algorithms and COX regression models were employed to further screen genes related to patient prognosis. Informed by both biological understanding and the outcomes of algorithms, we meticulously identified the ultimate set of liver metastasis-related gene (LRG). In the study of LRG genes, various databases were utilized to validate their association with pancreatic cancer liver metastasis. In order to analyze the effects of these agents on tumor microenvironment, we conducted an in-depth analysis, including changes in signaling pathways (GSVA), cell differentiation (pseudo-temporal analysis), cell communication networks (cell communication analysis), and downstream transcription factors (transcription factor activity prediction). Additionally, drug sensitivity analysis and metabolic analysis were performed to reveal the effects of LRG on gemcitabine resistance and metabolic pathways. Finally, functional experiments were conducted by silencing the expression of LRG in PANC-1 and Bx-PC-3 cells to validate its influence to proliferation and invasiveness on PANC-1 and Bx-PC-3 cells.ResultsThrough a series of algorithmic filters, we identified PAK2 as a key gene promoting pancreatic cancer liver metastasis. GSVA analysis elucidated the activation of the TGF-beta signaling pathway by PAK2 to promote the occurrence of liver metastasis. Pseudo-temporal analysis revealed a significant correlation between PAK2 expression and the lower differentiation status of pancreatic cancer cells. Cell communication analysis revealed that overexpression of PAK2 promotes communication between cancer cells and the tumor microenvironment. Transcription factor activity prediction displayed the transcription factor network regulated by PAK2. Drug sensitivity analysis and metabolic analysis revealed the impact of PAK2 on gemcitabine resistance and metabolic pathways. CCK8 experiments showed that silencing PAK2 led to a decrease in the proliferative capacity of pancreatic cancer cells and scratch experiments demonstrated that low expression of PAK2 decreased invasion capability in pancreatic cancer cells. Flow cytometry reveals that PAK2 significantly inhibited apoptosis in pancreatic cancer cell lines. Molecules related to the TGF-beta pathway decreased with the inhibition of PAK2, and there were corresponding significant changes in molecules associated with EMT.ConclusionPAK2 facilitated the angiogenic potential of cancer cells and promotes the epithelial-mesenchymal transition process by activating the TGF-beta signaling pathway. Simultaneously, it decreased the differentiation level of cancer cells, consequently enhancing their malignancy. Additionally, PAK2 fostered communication between cancer cells and the tumor microenvironment, augments cancer cell chemoresistance, and modulates energy metabolism pathways. In summary, PAK2 emerged as a pivotal gene orchestrating pancreatic cancer liver metastasis. Intervening in the expression of PAK2 may offer a promising therapeutic strategy for preventing liver metastasis of pancreatic cancer and improving its prognosis.

Abstract Background Antenatal depression (AD) is a major depressive disorder during pregnancy, which may lead to devastating sequelae for the expectant mothers and infants. This study aimed to investigate the prevalence, to analyze trajectory model based on EPDS score, and to explore the influence factors of AD among pregnant women in Chengdu, China. Methods Participants from four maternity hospitals in Chengdu, China were recruited when they had their first pregnancy medical check-up during March 2019 to May 2020. All participants were required to fill in Edinburgh Postnatal Depression Scale Chinese version (EPDS) once during three trimesters and provided information about their health status, social-demographic etc. The trajectory model, chi-square test and multivariate binary logistic regression were used to analyze all collected data. Results A total of 4560 pregnant women were recruited, while 1051 women completed the study. The prevalence of depression symptoms during the first, second and third trimesters were 32.92% (346/1051), 19.79% (208/1051) and 20.46% (215/1051) respectively. According to the results of the latent growth mixture modeling, the trajectory model of three categories based on EPDS score were identified in this study: low-risk group (38.2%, 401/1051), medium-risk group (54.8%, 576/1051) and high-risk group (7%, 74/1051). Good marital relationship (P = 0.007, OR = 0.33, 95% CI 0.147 ~ 0.74), good relationship with parents-in-law (P = 0.011, OR = 0.561, 95% CI 0.36 ~ 0.874), planned pregnancy (P = 0.018, OR = 0.681, 95% CI 0.496 ~ 0.936) were the protective factors while lower education level (P = 0.036, OR = 1.355, 95% CI 1.02 ~ 1.799), fear about dystocia (P = 0.0, OR = 1.729, 95% CI 1.31 ~ 2.283), recent major negative life events (P = 0.033, OR = 2.147, 95% CI 1.065 ~ 4.329) were the risk factors of medium-risk group. Good marital relationship (P = 0.005, OR = 0.2, 95% CI 0.065 ~ 0.615), good relationship with parents-in-law (P = 0.003, OR = 0.319, 95% CI 0.15 ~ 0.679) were also protective factors of high-risk group, but the risk factors for high-risk group were medical history (P = 0.046, OR = 1.836, 95% CI 1.011 ~ 3.334), pregnancy complications (P = 0.022, OR = 2.015, 95% CI 1.109 ~ 3.662), worry about dystocia (P = 0.003, OR = 2.365, 95% CI 1.347 ~ 4.153), recent major negative life events (P = 0.011, OR = 3.661, 95% CI 1.341 ~ 9.993). No protective or risk factors were identified for low-risk group. Conclusion Even the incidence and levels of depression in the first trimester of pregnancy were the highest, the probability of pregnancy women get depression during gestation period were higher than other population. Therefore, it’s important to monitor the psychological status of pregnant women during the whole pregnancy, especially in the first trimester. The study suggested a good partner relationship and good relations with parents-in-law both protected pregnant women from depression and promoted the well-being of mothers and children.

A20 gene variants are linked with systemic sclerosis (SS), but the mechanisms are unclear. Here, the authors show that A20 expression is reduced in SS skin and lungs, that its ablation in mice induces SS, and that show that fibrosis can be ameliorated by induction of A20.

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH–wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma–associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.

This paper is concerned with the existence and multiplicity of monotone positive solutions for a class of nonlinear fractional differential equation with a disturbance parameter in the integral boundary conditions on the infinite interval. By using Guo–Krasnosel’skii fixed-point theorem and the analytic technique, we divide the range of parameter for the existence of at least two, one and no positive solutions for the problem. In the end, an example is given to illustrate our main results.

The conservation management of natural ecosystems in China has significantly improved in recent decades, resulting in the effective protection of wildlife and the restoration of habitats. With the rapid growth in wildlife populations and corresponding range expansions, incidents of human–wildlife conflict have notably increased across China. However, only a few studies have paid adequate attention to wildlife damage management and compensation. In our review, we focus on the foremost mitigation measure to combat human–wildlife conflict, i.e., compensation for damage caused by wildlife. We conducted a questionnaire survey and an in-depth review of the literature across 19 Chinese provinces and autonomous regions, resulting in a total of 78 relevant sources. We first introduce the concept of wildlife damage compensation in China, followed by a review of Chinese legislation and policies regarding wildlife damage compensation. We compiled a comprehensive list of nuisance species, and we showcase four case studies in which we exemplarily describe the current situation of wildlife damage compensation. We reflect on difficulties and challenges such as delayed damage assessments or compensation quotas that do not correspond to current market prices. Since local legislation is often insufficient or completely absent, we make suggestions on how to improve existing policies and compensation mechanisms.

To investigate the feasibility of image colour information in predicting the moisture content of dried Hami jujube, the images were obtained under different colour space models, and the colour model component mean and chromaticity frequency sequences of R, G, B, H, S, V, L*, a* and b* were extracted through image analysis. After optimising the colour model component mean and chromaticity frequency sequence, the model was established and compared. The results showed that the GA-ELM (genetic algorithm - extreme learning machine) model established by CARS (competitive adaptive reweighted sampling) method to optimise 12 chromaticity features of S chromaticity frequency sequence had the best prediction effect, with Rc of 0.917, Rp of 0.934 and residual predictive deviation (RPD) of 2.507. Therefore, the colour image information can accurately predict the moisture content of dried Hami jujube.

Activation of TLR4 by its cognate damage-associated molecular patterns (DAMPs) elicits potent profibrotic effects and myofibroblast activation in systemic sclerosis (SSc), while genetic targeting of TLR4 or its DAMPs in mice accelerates fibrosis resolution. To prevent aberrant DAMP/TLR4 activity, a variety of negative regulators evolved to dampen the magnitude and duration of the signaling. These include radioprotective 105 kDa (RP105), a transmembrane TLR4 homolog that competitively inhibits DAMP recognition of TLR4, blocking TLR4 signaling in immune cells. The role of RP105 in TLR4-dependent fibrotic responses in SSc is unknown. Using unbiased transcriptome analysis of skin biopsies, we found that levels of both TLR4 and its adaptor protein MD2 were elevated in SSc skin and significantly correlated with each other. Expression of RP105 was negatively associated with myofibroblast differentiation in SSc. Importantly, RP105-TLR4 association was reduced, whereas TLR4-TLR4 showed strong association in fibroblasts from patients with SSc, as evidenced by PLA assays. Moreover, RP105 adaptor MD1 expression was significantly reduced in SSc skin biopsies and explanted SSc skin fibroblasts. Exogenous RP105-MD1 abrogated, while loss of RP105 exaggerated, fibrotic cellular responses. Importantly, ablation of RP105 in mice was associated with augmented TLR4 signaling and aggravated skin fibrosis in complementary disease models. Thus, we believe RP105-MD1 to be a novel cell-intrinsic negative regulator of TLR4-MD2–driven sustained fibroblast activation, representing a critical regulatory network governing the fibrotic process. Impaired RP105 function in SSc might contribute to persistence of progression of the disease.

This paper investigates the existence of a unique positive solution for a class of boundary value problems of p-Laplacian fractional differential equations, where its nonlinearity is signchanged and involves a fractional derivative term, and its boundary involves a nonlinear fractional integral term. By constructing an appropriate auxiliary boundary value problem and applying a generalized fixed point theorem of sum operator and properties of Mittag-Leffler function, some sufficient conditions for the existence of a unique positive solution are presented, and a monotone iterative sequence uniformly converging to the unique solution is constructed. In addition, an example is given to illustrate the main result.

Abstract Extrinsic factors, endocrine mechanisms, and behavioral indicators of migratory restlessness were studied in wintering whooper swans (Cygnus cygnus) in the Sanmenxia Swan National Wetland Park in western Henan Province, central China. First, the fecal glucocorticoid metabolite (FGM) concentration was established and related to mean air temperature or photo period (day length) using simple linear or non-linear regression models. After a model selection procedure, the best fitted model revealed that an increase of FGM concentration was associated with an increase in the squared mean air temperature (R2 = 0.88). Other models showed an increasing FGM concentration to correspond with increasing values of day length, squared day length, and mean air temperature—however without statistical support. In a second step, behavioral frequencies of seven behaviors were condensed into three behavioral principal components (PCs) using principal components analysis. Behavioral PCs largely corresponded to three activity phases described for wintering whooper swans in central China and were correlated with the FGM concentration using Spearman's rank-order correlations. Results revealed a significant correlation between FGM and behavioral PC2 (positive factor loadings from vigilance and preening, negative loading from foraging). Finally, we tested for an effect of behavioral PCs on changes in winter home range size using a set of multiple linear regression models. Results of averaged model parameter estimates showed only the behavioral PC3 (positive factor loadings from fighting and calling, negative loading from locomotion) had a marginal significant effect on home range size. Results confirmed findings of previous studies on migratory restlessness in whooper swans. However, due to the small sample size (N = 15 weeks) the effect of PC3 on home range size was weak and should be viewed with caution.

Prior studies reported inconsistent results on the altered gut microbial composition in patients with Crohn’s disease (CD), likely under the influences of many confounding factors including genetic, life style and environmental variations among different study cohorts. This study aims to examine the gut microbiota of CD patients with particular efforts to minimize the impact of the confounding factors. For this purpose, the healthy relatives of the patients were enrolled as control subjects so that the paired study subjects may have similar genetic background, dietary habits, and household environment. The fecal microbiota of the study subjects were examined by 16S rRNA sequencing. After the identification of the differential bacterial genera, multivariate regression analysis was performed to adjust the results for the impact of confounding factors. We found that the microbiota of the CD patients were featured with reduced short chain fatty acid (SCFA) producing bacteria and elevated opportunistic pathogen Escherichia-Shigella. Correlation analysis indicated that the elevation in Escherichia-Shigella and the reduction in SCFA-producing bacteria usually occur simultaneously. These differential genera exhibited a high capacity in distinguishing between CD and healthy controls achieving an area under curve of 0.89, and were correlated with the changes in inflammation related blood biochemical markers. Consistent with the reduction in SCFA-producing bacteria in CD, metabolomics analysis revealed decreased blood level of SCFAs in the patients. The differential genera identified in this study demonstrated outstanding capability to serve as diagnosis markers for CD and are potential targets for intervention.

High-throughput sequencing technology was used to establish the OTU (Operational Taxonomic Units) composition and diversity of bacteria and fungi in the gut of three family groups of Hainan gibbons (Nomascus hainanus) in the Bawangling National Nature Reserve on Hainan Island, southern China. Firmicutes (47.23%) and Bacteroidetes (36.54%) predominated at the phylum level, while the predominant genera were Prevotella-7 (15.30%), Lachnospiraceae_NK3A20_group (12.49%), and uncultured_bacterium_f_Erysipelotrichaceae (11.79%). At the phylum level, the dominant fungi were Ascomycota (66.41%), as well as Hanseniaspora (23.33%), Schwanniomyces (13.44%), and Pichia (5.43%) at the genus level. We found significant differences in the bacterial OTU diversity (Shannon index) between family groups living in Tropical Lowland or Tropical Montane Rain Forest, compared to those inhabiting Tropical Montane Evergreen Forest at higher altitudes. Bacterial OTU community composition also differed between family groups, unraveling significant differences among the 30 most dominant bacterial core taxa. Furthermore, we unraveled a significant difference of OTU richness in the fungal microbiome (Chao 1) between family groups living at lower altitudes, i.e., Tropical Lowland or Tropical Montane Rain Forest and those inhabiting the Tropical Montane Evergreen Forest. Our analysis further indicated significant differences in the fungal OTU community composition between the three family groups, especially regarding the three most dominant fungal core taxa. Subsequently, two habitat factors, and nine environmental and anthropogenic variables were used to explore possible causes of disparity in the microbial flora of gibbon groups. A factor reduction procedure resulted into three principal components which were correlated to bacterial and fungal OTU richness and diversity using Spearman's rank-order correlations. Bacterial and fungal OTU diversity was high in areas of high altitude, steep slopes, high tree density, but low tree height, while high fungal OTU richness corresponded to high altitude habitats, i.e., in the Tropical Montane Evergreen Forest. Distance to human settlements and to the next water body showed no significant relation with bacterial and fungal richness and diversity.

NLRP3 inflammasome is implicated in the pathogenesis of inflammatory bowel diseases (IBD). Since guanylate-binding protein 5 (GBP5) induces the NLRP3 inflammasome activity, we aim to investigate the potential role of GBP5 in IBD pathogenesis. The expression of GBP5, NLRP3 inflammasome, and related cytokines and chemokines was examined in two cohorts of IBD patients and healthy controls, by microarray transcriptome analysis and quantitative real-time PCR. Cellular localization of GBP5 in colonic biopsies was examined by immunohistochemistry and immunofluorescence with confocal microscopy. For functional studies, GBP5 was induced by interferon γ or silenced by siRNA or CRISPR/CAS9 technique, and inflammatory activities were evaluated at mRNA and protein levels. We found that the expression of GBP5 was elevated in colonic mucosa in two geographically and culturally distinct IBD cohorts. In colonic tissues of IBD patients, GBP5 expression was mainly confined to immune cells and the levels of GBP5 expression were correlated with those of the inflammatory cytokines and chemokines. In cultured T and macrophage cells, the expression of proinflammatory cytokines and chemokines was increased when GBP5 was induced, while GBP5 deficiency leads to decreased expression of proinflammatory mediators including gasdermin D, caspase 1, cytokines, and chemokines. We conclude that GBP5 is required in the expression of many proinflammatory cytokines and chemokines in intestinal immune cells. In addition, GBP5 may upregulate inflammatory reactions through an inflammasome-mediated mechanism. Since GBP5 plays a proinflammatory role at the early steps of the inflammatory cascades of IBD pathogenesis, and is implicated in IBD patients of distinct genetic and environmental backgrounds, targeting GBP5 could be an effective strategy for the management of IBD.

Abstract Background Low temperature (LT) often occurs at the seedling stage in the early rice-growing season, especially for direct seeded early-season indica rice, and using flooding irrigation can mitigate LT damage in rice seedlings. The molecular mechanism by which flooding mitigates the damage induced by LT stress has not been fully elucidated. Thus, LT stress at 8 °C, LT accompanied by flooding (LTF) and CK (control) treatments were established for 3 days to determine the transcriptomic, proteomic and physiological response in direct seeded rice seedlings at the seedling stage. Results LT damaged chloroplasts, and thylakoid lamellae, and increased osmiophilic bodies and starch grains compared to CK, but LTF alleviated the damage to chloroplast structure caused by LT. The physiological characteristics of treated plants showed that compared with LT, LTF significantly increased the contents of rubisco, chlorophyll, PEPCK, ATP and GA3 but significantly decreased soluble protein, MDA and ABA contents. 4D-label-free quantitative proteomic profiling showed that photosynthesis-responsive proteins, such as phytochrome, as well as chlorophyll and the tricarboxylic acid cycle were significantly downregulated in LT/CK and LTF/CK comparison groups. However, compared with LT, phytochrome, chlorophyllide oxygenase activity and the glucan branching enzyme in LTF were significantly upregulated in rice leaves. Transcriptomic and proteomic studies identified 72,818 transcripts and 5639 proteins, and 4983 genes that were identified at both the transcriptome and proteome levels. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were significantly enriched in glycine, serine and threonine metabolism, biosynthesis of secondary metabolites, glycolysis/gluconeogenesis and metabolic pathways. Conclusion Through transcriptomic, proteomic and physiological analyses, we determined that a variety of metabolic pathway changes were induced by LT and LTF. GO and KEGG enrichment analyses demonstrated that DEGs and DEPs were associated with photosynthesis pathways, antioxidant enzymes and energy metabolism pathway-related proteins. Our study provided new insights for efforts to reduce the damage to direct seeded rice caused by low-temperature stress and provided a breeding target for low temperature flooding-resistant cultivars. Further analysis of translational regulation and metabolites may help to elucidate the molecular mechanisms by which flooding mitigates low-temperature stress in direct seeded early indica rice at the seedling stage.

The pathophysiology of Alzheimer’s disease is thought to be directly linked to the abnormal aggregation of β-amyloid (Aβ) in the nervous system as a common neurodegenerative disease. Consequently, researchers in many areas are actively looking for factors that affect Aβ aggregation. Numerous investigations have demonstrated that, in addition to chemical induction of Aβ aggregation, electromagnetic radiation may also affect Aβ aggregation. Terahertz waves are an emerging form of non-ionizing radiation that has the potential to affect the secondary bonding networks of biological systems, which in turn could affect the course of biochemical reactions by altering the conformation of biological macromolecules. As the primary radiation target in this investigation, the in vitro modeled Aβ42 aggregation system was examined using fluorescence spectrophotometry, supplemented by cellular simulations and transmission electron microscopy, to see how it responded to 3.1 THz radiation in various aggregation phases. The results demonstrated that in the nucleation aggregation stage, 3.1 THz electromagnetic waves promote Aβ42 monomer aggregation and that this promoting effect gradually diminishes with the exacerbation of the degree of aggregation. However, by the stage of oligomer aggregation into the original fiber, 3.1 THz electromagnetic waves exhibited an inhibitory effect. This leads us to the conclusion that terahertz radiation has an impact on the stability of the Aβ42 secondary structure, which in turn affects how Aβ42 molecules are recognized during the aggregation process and causes a seemingly aberrant biochemical response. Molecular dynamics simulation was employed to support the theory based on the aforementioned experimental observations and inferences.

Low temperature (LT) chilling damage often occurs at the seedling stage of rice growth, especially direct-seeded early indica rice, and flooding can alleviate the damage caused by LT chilling at the rice seedling stage. However, few studies have elucidated the molecular mechanism by which suitable flooding alleviates LT stress-induced damage. Therefore, LT, LT plus flooding (LTF) and control (CK) treatments were established at 8 °C for 3 days to determine the phenotype, agronomic traits and transcriptomic of direct-seeded early indica rice at the seedling stage. The results showed that compared with LTF, the seedling height, root number, fresh weight, dry weight and T3 (the 3rd leaf from the top) leaf length significantly decreased after LT treatment; LTF could reduce the damage of LT to the agronomic characters of rice seedlings. The physiological characteristics showed that compared with LT, LTF significantly decreased soluble protein content and CAT activity. Transcriptomic profiling showed that 5934 DEGs were identified from the rice leaves between the LT and CK comparison groups; 7658 DEGs were identified between the LTF and CK; and 2697 DEGs were identified between the LT and LTF treatment. In biological process, the ‘metabolic process’ was the most enriched subcategory. In cellular components, the three most enriched subcategories were ‘cell’, ‘cell part’ and ‘organelle’. ‘Binding’ was the most enriched subcategory in molecular function. Differentially expressed genes (DEGs) were significantly enriched in photosynthesis, carotenoid biosynthesis, flavonoid biosynthesis, glycolysis gluconeogenesis, glycine, serine and threonine metabolism and plant hormone signal transduction pathways. Photosynthesis, energy metabolism and signal transduction pathway play important roles in flooding mitigation of LT stress. The results of this study may help to elucidate changes in physiological characteristics and gene expression through which flooding mitigates LT stress.

Systemic sclerosis (SSc) is a chronic, multisystem orphan disease with a highly variable clinical course, high mortality rate, and a poorly understood complex pathogenesis. We have identified an important role for a subpopulation of monocytes and macrophages characterized by surface expression of the scavenger receptor macrophage receptor with collagenous structure (MARCO) in chronic inflammation and fibrosis in SSc and in preclinical disease models. We show that MARCO+ monocytes and macrophages accumulate in lesional skin and lung in topographic proximity to activated myofibroblasts in patients with SSc and in the bleomycin-induced mouse model of SSc. Short-term treatment of mice with a potentially novel nanoparticle, poly(lactic-co-glycolic) acid (PLG), which is composed of a carboxylated, FDA-approved, biodegradable polymer and modulates activation and trafficking of MARCO+ inflammatory monocytes, markedly attenuated bleomycin-induced skin and lung inflammation and fibrosis. Mechanistically, in isolated cells in culture, PLG nanoparticles inhibited TGF-dependent fibrotic responses in vitro. Thus, MARCO+ monocytes are potent effector cells of skin and lung fibrosis and can be therapeutically targeted in SSc using PLG nanoparticles.

Abstract Background Physic nut (Jatropha curcas), an inedible oilseed plant, is among the most promising alternative energy sources because of its high oil content, rapid growth and extensive adaptability. Proteins encoded by MADS-box family genes are important transcription factors participated in regulating plant growth, seed development and responses to abiotic stress. However, there has been no in-depth research on the MADS-box genes and their roles in physic nut. Results In our study, 63 MADS-box genes (JcMADSs) were identified in the physic nut genome, and classed into five groups (MIKCC, Mα, Mβ, Mγ, MIKC*) according to phylogenetic comparison with Arabidopsis homologs. Expression profile analysis based on RNA-seq suggested that many JcMADS genes had the strongest expression in seeds, and seven of them responded in leaves to at least one abiotic stressor (drought and/or salinity) at one or more time points. Transient expression analysis and a transactivation assay indicated that JcMADS40 is a nucleus-localized transcriptional activator. Plants overexpressing JcMADS40 did not show altered plant growth, but the overexpressing plants did exhibit reductions in grain size, grain length, grain width, 1000-seed weight and yield per plant. Further data on the reduced grain size in JcMADS40-overexpressing plants supported the putative role of JcMADS genes in seed development. Conclusions This study will be useful in order to further understand the process of MADS-box genes involved in regulating growth and development in addition to their functions in abiotic stress resistance, and will eventually provide a theoretical basis for the functional investigation and the exploitation of candidate genes for the molecular improvement of physic nut.

Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut) or, less commonly, IDH2 (together called “IDHmut”). These mutations alter cellular biochemistry, and IDHmut gliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas. Some preclinical studies and clinical trials have suggested that various forms of a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, adherence to a strict KD is difficult, and not all studies have shown promising results. Furthermore, no study has yet addressed whether IDHmut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of a unrestricted, cycling KD (weekly alternating between KD and standard diet) in preclinical models of IDHwt versus IDHmut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDHwt or IDHmut glioma cells, either in low or normal glucose conditions. Likewise, an unrestricted, cycling KD had no effect on the in vivo growth of patient-derived IDHwt or IDHmut gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, this KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDHmut or IDHwt glioma. These data suggest that neither IDHwt nor IDHmut gliomas are particularly responsive to an unrestricted, cycling form of KD.

Infiltrative gliomas are the most common neoplasms arising in the brain, and remain largely incurable despite decades of research. A subset of these gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut) or, less commonly, IDH2 (together called "IDHmut"). These mutations alter cellular biochemistry, and IDHmut gliomas are generally less aggressive than IDH wild-type (IDHwt) gliomas. Some preclinical studies and clinical trials have suggested that various forms of a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial in slowing glioma progression. However, adherence to a strict KD is difficult, and not all studies have shown promising results. Furthermore, no study has yet addressed whether IDHmut gliomas might be more sensitive to KD. The aim of the current study was to compare the effects of a unrestricted, cycling KD (weekly alternating between KD and standard diet) in preclinical models of IDHwt versus IDHmut gliomas. In vitro, simulating KD by treatment with the ketone body β-hydroxybutyrate had no effect on the proliferation of patient-derived IDHwt or IDHmut glioma cells, either in low or normal glucose conditions. Likewise, an unrestricted, cycling KD had no effect on the in vivo growth of patient-derived IDHwt or IDHmut gliomas, even though the cycling KD did result in persistently elevated circulating ketones. Furthermore, this KD conferred no survival benefit in mice engrafted with Sleeping-Beauty transposase-engineered IDHmut or IDHwt glioma. These data suggest that neither IDHwt nor IDHmut gliomas are particularly responsive to an unrestricted, cycling form of KD.

The basis of sexual dimorphism in non-model species may be elusive, in part due to a lack of genomic and molecular resources. Here, Li et al. report a high-quality anuran genome and reveal candidate genes and pathways associated with shaping sexually dimorphic nuptial spines in a moustache toad.

BackgroundsAs a crucial enzyme in thyroid hormone synthesis, the genetic defective thyroid peroxidase (TPO) was one of the main genetic factors leading to congenital hypothyroidism (CH).MethodsMutations in the TPO gene were screened and identified in 219 patients with CH from northwest China by using high-throughput sequencing and bioinformatics analysis. The biological function of detected variants was studied by in vitro experiments and homology modeling.ResultsNineteen rare variants, including seven novel ones, were detected in 17 of 219 patients (7.8%). Most cases were detected with one single heterozygous variant, and only two patients were detected with multiple variants, i.e., compounds for (1) IVS7-1G>A, p.Ala443Val, and p.Arg769Trp and (2) p.Asn592Ser and p.Asn798Lys. The biological function of the four missense mutations (i.e., p.Ala443Val, p.Arg769Trp, p.Asn592Ser, and p.Asn798Lys) they carried were further studied. Experimental data showed that these four mutations did not affect the protein expression level of the TPO gene but remarkably reduced the peroxidase activity toward guaiacol oxidation, retaining 8–32% of activity of the wild-type protein. The comparison of the predicted 3-D structures of wild-type and mutant TPO proteins showed that these four amino acid substitutions changed the non-covalent interactions of studied residues that might alter the structure and function of the TPO protein.ConclusionThis study was the first to analyze the TPO mutation spectrum of patients with CH in northwest China. Our data indicated that the TPO mutation was not a common reason to cause CH in China. The functional data may help to clarify the structure-function relationship of the TPO protein and provide further evidence for the elucidation of the genetic etiology of CH.

The Oriental white stork (Ciconia boyciana), with a global population of roughly 2500, is listed as endangered by IUCN. To date, little is known about its behaviors, particularly on migration, habitat use and their ontogenic differences. In this study, we tracked 11 Oriental White storks (9 juveniles and 2 adults) rescued in Sanjiang Plain and investigated their migration behaviors and survival rates using GPS/GSM telemetry. The results show that all the rescued individuals joined the wild migrating groups, but the migration routes of juvenile birds are highly variable compared to adult ones. From its breeding grounds of the Songnen/Sanjiang Plains to the wintering grounds in middle reaches of the Yangtze River, there is no significant correlation in habitat selections by adult birds, as wetlands being their first choice. In contrast, a positive correlation in juveniles’ selection has been identified over artificial habitats such as rice paddies and fish farms，which could lead to human-wild conflicts and affect the survival of juvenile storks. In this study, eight out of nine juveniles dies in the end of tracking. Our study exposes negative consequences of inappropriate release of rescued wild animals (especially juveniles) on species survival, and thus provides scientific guidelines to the future situations alike. Moreover, it is necessary to reduce the direct contact between humans and rescued animals, so that their dependence on artificial environments could be reduced, which could benefit the species’ long term survival, especially for the rescued population.

Life-history theory predicts that increased resource allocation in current reproduction comes at the cost of survival and future reproductive fitness. In taxa with biparental care, each parent can adjust investment on current reproduction according to changes in their partner’s effort, but these adjustments may be different for males and females as they may have different reproductive strategies. Numerous theoretical and empirical studies have proposed the mechanism underlying such adjustments. In addition, the value of the brood or litter (brood size) has also been suggested to affect the amount of care through manipulation of brood size. While the two conditions have been studied independently, the impact of their interplay on potential sex-dependent future reproductive performance remains largely unknown. In this study, we simultaneously manipulated both care system (removal of either parent vs. no removal) and brood size in a burying beetle (Nicrophorus vespilloides) to understand their joint effect on reproductive allocation and trade-off between current and future reproduction. Our results show that males compensated for mate loss by significantly increasing the level of care regardless of brood size, while females exhibited such compensation only for small brood size. Additionally, with an increase in allocation to current reproduction, males showed decreased parental investment during the subsequent breeding event as a pair. These findings imply a dual influence of parental care system and brood size on allocation in current reproduction. Moreover, the impact of such adjustments on sex-dependent differences in future reproduction (parental care, larvae number, and average larval mass at dispersal) is also demonstrated. Our findings enhance the understanding of sex roles in parental investment and highlight their importance as drivers of reproductive allocation.

Sphingosine-1-phosphate (S1P) is a phospholipid that regulates pleiotropic biological activities and exerts extracellular functions by binding to five specific G-protein-coupled receptors, S1P receptors (S1PR) 1–5. When activated by S1P, S1PR promote the proliferation and invasion of tumor cells by inducing the formation of new blood vessels. We developed and assessed a new monoclonal antibody imaging probe 99mTc-HYNIC-S1PR1mAb, to explore the feasibility of targeting the S1PR1 in vitro and in vivo. S1PR1mAb was prepared and followed by technetium-99m labeling with succinimidyl 6-hydraziniumnicotinate hydrochloride. Cell uptake and blocking studies were performed to investigate the binding specificity of 99mTc-HYNIC-S1PR1mAb in vitro. 99mTc-HYNIC-S1P1mAb was also tested in vivo in mice xenografted with SK-HEP-1 (high-expression of S1PR1) and MCF-7 (low-expression of S1PR1) using single-photon emission-computed tomography (SPECT). Ex vivo gamma counting of tissues from tumor-bearing mice was used to evaluate 99mTc-HYNIC-S1PR1mAb biodistribution. The biodistribution study results showed significantly higher uptake in SK-HEP-1 tumors than in MCF-7 tumors (P < 0.001). Reduced uptake of 99mTc-HYNIC-S1PR1mAb in SK-HEP-1 was observed in tumor-bearing nude mice pretreated with fingolimod, which binds competitively to the receptors, especially S1PR1. 99mTc-HYNIC-S1PR1mAb can be synthesized and specifically targeted to S1PR1 in vitro and in vivo, allowing S1PR1 expression assessment with SPECT imaging.

There are many and diverse intestinal microbiota, and they are closely related to various physiological functions of the body. They directly participate in the host's food digestion, nutrient absorption, energy metabolism, immune response, and many other physiological activities and are also related to the occurrence of many diseases. The intestinal microbiota are extremely important for maintaining normal physical health. In order to explore the composition and differences of the intestinal microbiota of whooper swans in different wintering areas, we collected fecal samples of whooper swans in Sanmenxia, Henan, and Rongcheng, Shandong, and we used the Illumina HiSeq platform to perform high-throughput sequencing of bacterial 16S rRNA genes. Comparison between Sanmenxia and Rongcheng showed no significant differences in ACE, Chao 1, Simpson, and Shannon indices (p > 0.05). Beta diversity results showed significant differences in bacterial communities between two groups [analysis of similarity (ANOSIM): R = 0.80, p = 0.011]. Linear discriminant analysis effect size (LEfSe) analysis showed that at the phylum level, the relative abundance of Actinobacteria was significantly higher in Sanmenxia whooper swans than Rongcheng whooper swans. At the genus level, the amount of Psychrobacter and Carnobacterium in Sanmenxia was significantly higher in Rongcheng, while the relative abundance Catellicoccus and Lactobacillus was significantly higher in Rongcheng than in Sanmenxia. This study analyzed the composition, characteristics, and differences of the intestinal microbiota of the whooper swans in different wintering environments and provided theoretical support for further exploring the relationship between the intestinal microbiota of the whooper swans and the external environment. And it played an important role in the overwintering physiology and ecology, population management, and epidemic prevention and control of whooper swans.

Abstract This paper is concerned with the impact of the parameter on the existence of different types of solutions for a class of nonlinear fractional integral boundary value problems with a parameter that causes the sign of Green’s function associated with the BVP to change. By using the Guo–Krasnoselskii fixed point theorem, the Leray–Schauder nonlinear alternative, and the analytic technique, we give the range of the parameter for the existence of strong positive solutions, strong negative solutions, negative solutions, and sign-changing solutions for the boundary value problem. Some examples are given to illustrate our main results.

Summary: The processes underlying synchronous multiple organ fibrosis in systemic sclerosis (SSc) remain poorly understood. Age-related pathologies are associated with organismal decline in nicotinamide adenine dinucleotide (NAD+) that is due to dysregulation of NAD+ homeostasis and involves the NADase CD38. We now show that CD38 is upregulated in patients with diffuse cutaneous SSc, and CD38 levels in the skin associate with molecular fibrosis signatures, as well as clinical fibrosis scores, while expression of key NAD+-synthesizing enzymes is unaltered. Boosting NAD+ via genetic or pharmacological CD38 targeting or NAD+ precursor supplementation protected mice from skin, lung, and peritoneal fibrosis. In mechanistic experiments, CD38 was found to reduce NAD+ levels and sirtuin activity to augment cellular fibrotic responses, while inhibiting CD38 had the opposite effect. Thus, we identify CD38 upregulation and resulting disrupted NAD+ homeostasis as a fundamental mechanism driving fibrosis in SSc, suggesting that CD38 might represent a novel therapeutic target.

Nb-doped ZnO thin films were fabricated on glass substrates by using co-sputtering with direct-current and radio frequency magnetron sputtering. The structures, optical and electrical performances of Nb-doped ZnO thin films were investigated. The results showed that all thin films have (0 0 2) c-axis preferential orientation. The minimum resistivity of 2.12×10−3Ωcm and the maximum carrier concentration of 2.39×1019cm−3 were obtained at the direct-current sputtering power of 10W, respectively. Nb-doped ZnO thin films have also shown high average transmittance of 89.6%, and lower surface roughness of 2.74nm. Meanwhile, a distinct absorption edge in the ultraviolet range of 300–400nm was observed in absorbance, the optical band gap of Nb-doped ZnO thin films illustrates an increased tendency with increasing Nb concentration.

Gliosis and fibrosis after spinal cord injury (SCI) lead to formation of a scar that is an impediment to axonal regeneration. Fibrotic scarring is characterized by the accumulation of fibronectin, collagen, and fibroblasts at the lesion site. The mechanisms regulating fibrotic scarring after SCI and its effects on axonal elongation and functional recovery are not well understood. In this study, we examined the effects of eliminating an isoform of fibronectin containing the Extra Domain A domain (FnEDA) on both fibrosis and on functional recovery after contusion SCI using male and female FnEDA-null mice. Eliminating FnEDA did not reduce the acute fibrotic response but markedly diminished chronic fibrotic scarring after SCI. Glial scarring was unchanged after SCI in FnEDA-null mice. We found that FnEDA was important for the long-term stability of the assembled fibronectin matrix during both the subacute and chronic phases of SCI. Motor functional recovery was significantly improved, and there were increased numbers of axons in the lesion site compared to wildtype mice, suggesting that the chronic fibrotic response is detrimental to recovery. Our data provide insight into the mechanisms of fibrosis after SCI and suggest that disruption of fibronectin matrix stability by targeting FnEDA represents a potential therapeutic strategy for promoting recovery after SCI.

Abstract Background Zanthoxylum acanthopodium has insecticidal effect in Chinese traditional medicine. In this study, the essential oil from the dried Zanthoxylum plant was used as a larvicidal compound against the malaria mosquitoes, Anopheles anthropophagus and Anopheles sinensis. Methods Compounds in the Zanthoxylum essential oil were investigated by gas chromatography and mass spectroscopy (GC–MS). The larvicidal bioassays of the whole oil, as well as the main compounds in the oil (estragole and eucalyptol) were performed using WHO method. Results In total, 63 main compounds (99.32%) were found in the oils, including estragole (15.46%), eucalyptol (10.94%), β-caryophyllene (5.52%), cis-linalool oxide (3.76%), cis-limonene oxide (3.06%). A dose-dependent effect on mortality was recorded with increasing concentrations of essential oil and compounds increasing mortality of the larvae. Larvicidal bioassays revealed that 24 h LC50 of the whole essential oil was 36.00 mg/L and LC90 was 101.49 mg/L against An. anthropophagus, while LC50 was 49.02 mg/L and LC90 was 125.18 mg/L against An. sinensis. Additionally, 24 h LC50 of estragole were 38.56 and 41.67 mg/L against An. anthropophagus and An. sinensis, respectively, while the related LC90 were 95.90 and 107.89 mg/L. LC50 of eucalyptol were 42.41 and 45.49 mg/L against An. anthropophagus and An. sinensis, while the related LC90 were 114.45 and 124.95 mg/L. Conclusion The essential oil of Z. acanthopodium and its several major compounds may have potential for use in the control of malaria mosquitoes.

Elastic beam is a kind of mathematical model in elastic mechanics and engineering physics. For now, this type of model is often used in real life. On the basis of the relative research on the elastic beam equations with one end fixed and one end sliding support, and the multiple solutions of the elastic beam equation are researched. In this paper, through putting this problem into an integral equation, which is equivalent to an operator fixed-point problem, and combining with the properties of Green function and Guo- Krasnoselskii fixed point theorem of cone expansion and compression, the existence of positive solutions of this kind of elastic beam equations is discussed. Under various assumptions on nonlinear terms, the intervals of the parameters are established, and the existence of one positive solution, two positive solutions or nonexistence of positive solutions for this elastic beam equations are obtained. In conclusion, the intervals of eigenvalue about this problem for at least one positive solution, two positive solutions and nonexistence of positive solutions are obtained. The study of the existence of such solution can not only contribute to the stability analysis of elastic beams, but also enrich the theory of material mechanics.

Physiological stress in captive wild animals may be caused by stressors such as capture, handling, and transport. Continuous strong stimulation may induce a long-term physiological stress in captive wild animals after transport. Fecal Glucocorticosteroid Metabolites (FGM), vital signs and behavioral changes were used to establish stress responses of white rhinoceros during a translocation process. The result indicated that the overall FGM increased significantly (p

Systemic sclerosis (SSc) is a fibrotic disease affecting multiple organs. Here the authors use patient samples plus mouse studies to show a central role for tenascin C as a TLR4 activator responsible for persistence of fibrosis in the context of SSc and SSc-like disease.

Systemic sclerosis (SSc) is a poorly understood heterogeneous condition with progressive multi-organ fibrosis. Recent genetic and genomic evidence suggest a pathogenic role for dysregulated innate immunity and toll-like receptor (TLR) activity in SSc. Levels of both TLR4, as well as certain endogenous TLR ligands, are elevated in skin and lung tissues from patients with SSc and correlate with clinical disease parameters. Conversely, genetic targeting of TLR4 or its endogenous “damage-associated” ligands ameliorates progressive tissue fibrosis. Targeting TLR4 signaling therefore represents a pharmacological strategy to prevent intractable fibrosis. We examined the effect of TAK242, a small molecule TLR4 inhibitor, in preclinical fibrosis models and in SSc fibroblasts. TAK242 treatment prevented, promoted regression of, bleomycin-induced dermal and pulmonary fibrosis, and reduced the expression of several pro-fibrotic mediators. Furthermore, TAK242 ameliorated peritoneal fibrosis and reduced spontaneous hypodermal thickness in TSK/+ mice. Importantly, TAK242 abrogated collagen synthesis and myofibroblasts differentiation in explanted constitutively active SSc fibroblast. Altogether, these findings identify TAK242 as an anti-fibrotic agent in preclinical models of organ fibrosis. TAK242 might potentially represent a novel strategy for the treatment of SSc and other fibrotic diseases.

Regular usage of NaOH/NaClO disinfectants results in high sodium salt and alkalinity of poultry manure. This study compared three amendments: vegetable waste (V), food waste (F) and mature compost (C) for their ability to improve the composting of NaOH/NaClO-contaminated poultry manure. C compost resulted in the highest compost temperatures (p

Heat generation model of high speed cylindrical roller bearing is constructed by calculating the local friction in the bearing. Bubble flow calculation model of roller bearing considering fluid-solid thermal coupling is constructed based on two-body fluid model and k-ε turbulent model, in which diameter and size of bubbles, breakup, and coalescence model of bubbles are considered. Using dynamic mesh method, a new method for evaluating bearing temperature is set up treating the rolling elements as moving heat sources. Based on these models and finite element method, bubble flow of a high speed roller bearing is studied based on FLUENT software. The numerical study reveals the relationship between velocity of bearing, air volume fraction, and velocity and pressure of oil-air flow. An increase of air content in the oil produces a lower pressure at the bearing outlet while the exit fluid velocity increases. When fluid-solid thermal coupling effect is considered, velocity and pressure at outlet of the bearing both become larger, while temperature of bearing is lower than that without coupling. In comparison, the coupling effects on flow pressure and temperature are obvious. For a given rotating speed, there is an optimal value for air volume fraction, such that temperature rise of the bearing reaches the lowest value. Experiments verify the outcomes of the method presented in this paper.

Calcium alginate (CaAlg) submicroparticles have a potential application in agricultural delivery systems. This study investigated the effects of CaAlg submicroparticles on seed germination and seedling growth of wheat. CaAlg submicroparticles with a Z-average diameter of around 250.4 nm and a measured zeta potential value of about −25.4 mV were prepared and characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy dispersive X-ray spectrometer (EDS). After this, the effects of the concentration of CaAlg submicroparticles (10–500 μg/mL) on germination percentage, seedling length, the number of adventitious roots, chlorophyll content and soluble protein content were evaluated. The results demonstrated a significant increase in the level of germination percentage (9.0%), seedling index (50.3%), adventitious roots (27.5%), seedling length (17.0%), chlorophyll (8.7%) and soluble protein contents (4.5%) at a concentration of 100 μg/mL. However, an inhibitory effect was observed at a concentration of 500 μg/mL. The SEM examination showed that CaAlg submicroparticles could be successfully adsorbed onto the surface of the wheat seed. Further studies proved that CaAlg submicroparticles at a concentration of 100 μg/mL promoted the expression of indole-3-acetic acid (IAA)-related genes (YUCCA9, AUX1, ARF and UGT) in wheat, which resulted in an increase of 69% and 21% in IAA concentration in wheat roots and shoots, respectively.

Chitosan oligosaccharide (COS), derived through hydrolysis of chitosan, has been proved to be an effective plant immunity elicitor, eco-friendly, and easily soluble in water, and influenced several secondary metabolites content to improve fruit qualities. COS are widely used in agriculture to improve the defense response in plants. The purpose of this study was to investigate the pre-harvest treatment effect of COS on the quality of strawberry (Fragaria × ananassa cv.qingxiang). COS was dissolved in distilled water at a concentration of 50 mg·L−1 and sprayed at four different growth stages of strawberry plants, namely seedling stage, before flowering, fruit coloring (the stage of fruit from white to red) and full bloom. Uniform size, shape, color, without any visible damage, and disease-free fruits were harvested for determining the quality. The results showed that the fruit firmness, viscosity, lignin, sugars, protein, total soluble solid, and titratable acidity content increased in COS-treated fruits compared to control. In addition, COS pre-harvest treatment had a positive effect on anthocyanin, total phenol, flavonoid, vitamin C content and DPPH(2,2-diphenyl-1-picrylhydrazyl) scavenging activity of strawberry. Moreover, COS also increased the cell wall composition and regulated gene expression of some important enzymes involved in ethylene compound biosynthesis and cell wall degradation. The finding of this study suggests that pre-harvest application of COS is very useful for improving quality and antioxidant capacity of strawberry.

The title compound, C16H16N2O4, was obtained from the reaction of hydrazine hydrate and o-vanilin in absolute ethanol. The molecule is almost planar (except for the methyl H atoms), with a mean deviation from the plane of 0.0259 Å. The molecular structure also exhibits an approximate non-crystallographic twofold axis. Intramolecular O—H...N hydrogen bonds occur. In the crystal, intermolecular C—H...O hydrogen bonds generate molecular zigzag sheets. The sheets stack through C—H...π interactions, leading to a three-dimensional-network.

Abstract Background The muskrat is a seasonal breeder. Males secrete musk to attract females during the breeding season. The testosterone binding to the androgen receptor (AR) in musk glands of muskrat may play an important role conducting the musk secretion process. Methods The musk gland, testis and blood samples of musk rats are collected in both breeding and non-breeding seasons. Some part of the samples are kept in liquid nitrogen for transcriptome analysis and Western blotting test. Some part of the samples are kept in 70% alcohol for histology experiment, blood samples are kept at −20 °C for the serum testosterone measurement experiment. Results This study demonstrates that the quantity of secreted musk, the volume of the musk glands, the diameter of the gland cells and AR expression are all higher during the breeding season than at other times (p < 0.01). StAR, P450scc and 3β-HSD expression in the Leydig cells of the testis were also higher during this season, as was serum testosterone. AR was also observed in the gland cells of two other musk-secreting animals, the musk deer and small Indian civet, in their musk glands. These results suggest that the testes and musk glands co-develop seasonally. Conclusion The musk glands’ seasonal development and musk secretion are regulated by the testes, and testosterone plays an important role in the seasonal development of musk glands.