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Background: Nur77 belongs to the member of orphan nuclear receptor 4A family that plays critical roles in maintaining vascular homeostasis. This study aims to determine whether Nur77 plays a role in attenuating vascular dysfunction, and if so, to determine the molecular mechanisms involved. Methods: Both Nur77 knockout (Nur77 KO) and Nur77 endothelial specific transgenic mice (Nur77-Tg) were employed to examine the functional significance of Nur77 in vascular endothelium in vivo. Endothelium-dependent vasodilatation to acetylcholine (Ach) and reactive oxygen species (ROS) production was determined under inflammatory and high glucose conditions. Expression of genes was determined by real-time PCR and western blot analysis. Results: In response to tumor necrosis factor alpha (TNF-α) treatment and diabetes, the endothelium-dependent vasodilatation to Ach was significantly impaired in aorta from Nur77 KO as compared with those from the wild-type (WT) mice. Endothelial specific overexpression of Nur77 markedly prevented both TNF-α- and high glucose-induced endothelial dysfunction. Compared with WT mice, after TNF-α and high glucose treatment, ROS production in aorta was significantly increased in Nur77 KO mice, but it was inhibited in Nur77-Tg mice, as determined by dihydroethidium (DHE) staining. Furthermore, we demonstrated that Nur77 overexpression substantially increased the expression of several key enzymes involved in nitric oxide (NO) production and ROS scavenging, including endothelial nitric oxide synthase (eNOS), guanosine triphosphate cyclohydrolase 1 (GCH-1), glutathione peroxidase-1 (GPx-1), and superoxide dismutases (SODs). Mechanistically, we found that Nur77 increased GCH1 mRNA stability by inhibiting the expression of microRNA-133a, while Nur77 upregulated SOD1 expression through directly binding to the human SOD1 promoter in vascular endothelial cells. Conclusion: Our results suggest that Nur77 plays an essential role in attenuating endothelial dysfunction through activating NO production and anti-oxidant pathways in vascular endothelium. Targeted activation of Nur77 may provide a novel therapeutic approach for the treatment of cardiovascular diseases associated with endothelial dysfunction.

The formation and stability of soil aggregates affect plant growth, carbon sequestration, and many other physiological and biogeochemical processes. Aggregates may be destabilized by nitrogen (N) deposition due to decreased inputs of binding materials; however, the legacy effects of which are unknown. An increase in labile carbon (C) input could mitigate the negative impacts of N addition on soil aggregate stability through the improvement of soil physical, chemical and biological conditions. Using a field experiment with the addition of NH4NO3 at multiple levels in a meadow steppe, we terminated the addition of N at the sixth year and shifted to applying labile C in the form of sucrose at three levels (C-0, C-200, and C-2000 g C m−2 y−1) to soil for two years. Then we examined the aggregate size distribution and the associated soil properties. The high historical N addition rates decreased the proportion of macroaggregates (>2000 μm) and increased microaggregates (

This study aims to synthesize composite materials using TC4 particles and AZ91D alloy through semi-solid stirring and hot extrusion techniques. The main objective is to investigate the microstructure, mechanical properties, wear resistance, and corrosion behavior of composites comprising a minor volume fraction (0, 2, and 5 vol%) of spherical TC4 particles. The findings showed that the dual synergistic effect of TC4 particles and the β-phase leads to a refinement in the grain size of the composite material. Moreover, the incorporation of TC4 particles enhances the hardness, yield strength (YS), and ultimate tensile strength (UTS) of the magnesium matrix, with almost no reduction observed in ductility. Additionally, the TC4/AZ91D composite displays lower wear rates and friction coefficients compared to the matrix when subjected to forces of 150 N and 300 N. However, the corrosion performance of the composite material deteriorates due to the influence of the galvanic effect between the particles and the matrix.

AbstractPurpose Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire.Methods This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively.Results This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models.Conclusion Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Abstract Background This cross‐sectional study aimed to identify latent sensitization profiles of asthma patients in mainland China, unveiling the association between regional differences and sensitization patterns. Methods 1056 asthma participants from 10 medical centers divided into eastern and western cohorts were clustered into four individual sensitization patterns, respectively, by using an unsupervised statistical modeling method, latent class analysis (LCA), based on the levels of 12 aeroallergens specific IgE reactivities. Moreover, differences in clinical characteristics and environmental exposures were compared in different sensitization patterns. Results Four distinct sensitization patterns in the two cohorts were defined as follows, respectively. Eastern cohort: Class 1: “High weed pollen and house dust mites (HDMs) sensitization” (8.87%), Class 2: “HDMs dominated sensitization” (38.38%), Class 3: “High HDMs and animal dander sensitization” (6.95%), Class 4: “Low/no aeroallergen sensitization” (45.80%). Western cohort: Class 1: “High weed pollen sensitization” (26.14%), Class 2: “High multi‐pollen sensitization” (15.02%), Class 3: “HDMs‐dominated sensitization” (10.33%), Class 4: “Low/no aeroallergen sensitization” (48.51%). Of note, the significant statistical difference in age, asthma control test score (ACT) and comorbidities were observed within or between different sensitization patterns. Exposure factors in different sensitization patterns were pointed out. Conclusions Asthmatic patients with distinct sensitization patterns were clustered and identified through the LCA method, disclosing the relationship between sensitization profiles of multiple aeroallergens and geographical differences, providing novel insights and potential strategies for atopic disease monitoring, management and prevention in clinical practice.

With the growing consumption power of Generation Z and the accelerated development of digital technology in China, the market of domestic makeups is on the rise. Meanwhile, various digital platforms have become the main channel for the promotion of national beauty brands. Therefore, the dissemination of domestic cosmetics information on digital platforms remains a discussion that when social content includes Chinese ethnic elements, whether the audience’s recognition of Chinese national identity can be enhanced. Based on the Stimulus-Organism-Response (S-O-R) model, with brand familiarity and media richness as independent variables, knowledge of ethnic elements and cognitive cultural intelligence as moderators, as well as cultural perception as mediators, this study investigates digital communication effects on the recognition of Chinese national identity by exploring ethnic elements in different Chinese makeup brands. The research adopts an experimental method and find that: (1) media richness significantly affects audiences’ cultural perception, and cultural perception play a mediating role in the effect of media richness on Chinese national identity; (2) the knowledge of ethnic elements in Chinese makeups negatively moderates the effect of media richness on culture perception; (3) cognitive cultural intelligence intensifies the link between cultural perception and Chinese national identity; (4) brand familiarity positively affects Chinese national identity while it has a negative impact cultural perception. This paper proves the assumptions effectively, and the findings could be expanded to promote digital communication of Chinese culture in the context of national cosmetics brands.

Proinflammatory agonists provoke the expression of cell surface adhesion molecules on endothelium in order to facilitate leukocyte infiltration into tissues. Rigorous control over this process is important to prevent unwanted inflammation and organ damage. Protein L-isoaspartyl O-methyltransferase (PIMT) converts isoaspartyl residues to conventional methylated forms in cells undergoing stress-induced protein damage. The purpose of this study was to determine the role of PIMT in vascular homeostasis. PIMT is abundantly expressed in mouse lung endothelium and PIMT deficiency in mice exacerbated pulmonary inflammation and vascular leakage to LPS(lipopolysaccharide). Furthermore, we found that PIMT inhibited LPS-induced toll-like receptor signaling through its interaction with TNF receptor-associated factor 6 (TRAF6) and its ability to methylate asparagine residues in the coiled-coil domain. This interaction was found to inhibit TRAF6 oligomerization and autoubiquitination, which prevented NF-κB transactivation and subsequent expression of endothelial adhesion molecules. Separately, PIMT also suppressed ICAM-1 expression by inhibiting its N-glycosylation, causing effects on protein stability that ultimately translated into reduced EC(endothelial cell)-leukocyte interactions. Our study has identified PIMT as a novel and potent suppressor of endothelial activation. Taken together, these findings suggest that therapeutic targeting of PIMT may be effective in limiting organ injury in inflammatory vascular diseases.

Summary: Background: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial β3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure. Methods: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with LC-MS/MS were used to identify the phosphorylation site of Nur77 activated by Mst1. The phosphorylated Nur77 was detected by phos-tag SDS-PAGE assay and specific antibody against phospho-Nur77-Thr366. The effect of embryo-epithelium interaction was determined in the BeWo spheroid or mouse embryo adhesion assay, and delayed implantation mouse model. RNA-seq was used to explore the mechanism by which Nur77 derived peptide promotes endometrial receptivity. Findings: Endometrial Mammalian sterile 20 (STE20)-like kinase 1 (Mst1) expression level was decreased in the women with RIF than that in the fertile control group, while Mst1 activation in the epithelial cells promoted trophoblast–uterine epithelium adhesion. The effect of Nur77 mediated trophoblast–uterine epithelium adhesion was facilitated by active Mst1. Mechanistically, mst1 promotes the transcription activity of Nur77 by phosphorylating Nur77 at threonine 366 (T366), and consequently increased downstream target β3-integrin expression. Furthermore, a Nur77-derived peptide containing phosphorylated T366 markedly promoted mouse embryo attachment to Ishikawa cells ([4 (2–4)] vs [3 (2–4)]) and increased the embryo implantation rate (4 vs 1.4) in a delayed implantation mouse model by regulating integrin signalling. Finally, it is observed that the endometrial phospho-Nur77 (T366) level is decreased by 80% in the women with RIF. Interpretation: In addition to uncovering a potential regulatory mechanism of Mst1/Nur77/β3-integrin signal axis involved in the regulation of embryo-epithelium interaction, our finding provides a novel marker of endometrial receptivity and a potential therapeutic agent for embryo implantation failure. Funding: National Key Research and Development Program of China (2018YFC1004400), the National Natural Science Foundation of China (82171653, 82271698, 82030040, 81971387 and 30900727), and National Institutes of Health grants (R01HL103869).

The influence of landscape structure on species communities is intimately connected to the spatial scales at which measurements are made. If we do not measure landscape structure at its most impactful scale, otherwise known as the “scale of effect”, we might fail to detect crucial community–landscape relationships. In our study, we focused on the “scale of effect” as it pertains to the relationship between urban bird diversity and landscape structure. We investigated eight types of landscape structure variables alongside elevation attributes across 16 spatial scales around 28 sampling sites in Kunming, Yunnan Province, China. Our objective was to identify the most influential scale at which the environmental variables under investigation affect the taxonomic and functional diversity of bird species. We utilized PLSR and VIP scores to overcome challenges posed by multicollinearity among predictors. We found that the influence of landscape characteristics on bird species richness and functional dispersion index (FDis) was scale-dependent. Notably, the influence of the area of open water on FDis is most pronounced at smaller scales, while at larger scales, open water dispersion becomes more essential. Additionally, in a highly fragmented urban matrix, the importance of forest connectivity may exceed that of patch size at medium scales. However, the significance of forest coverage increases with scale, which underscores the importance of preservation efforts at larger scales to prevent forest fragmentation. We also noted a considerable impact from landscape-level subdivision across almost all scales. These findings highlight the importance of shifting urban conservation planning towards a multi-scale approach, which would allow for the identification of priority intervention scales.

Abstract Background The clinical characteristics of patients with chronic cough are reported only in single-center survey in China, being significantly different from that in western countries. Here, we performed a multicenter study to describe the clinical characteristics of chronic cough patients. Methods A cross-sectional observational survey was conducted in thirteen tertiary hospitals of Guangdong, South China. Relevant data were recorded using a standardized questionnaire and analyzed, including demographics, educational attainment, cough features, and concomitant symptoms. Results Of 933 patients in this study, the median age was 40.0 (IQR 31.0–52.0) years with a peaked age of 30–39 years. The proportion of females (487, 52.2 %) was comparable to that of males (446, 47.8 %). Up to 81.9 % of the patients were non-smokers. More than two-thirds of the subjects with chronic cough had a low educational level. The median cough duration was 6.0 (IQR 3.0–24.0) months, and 73.0 % of chronic cough patients presented with dry cough. Laryngeal paresthesia was the most common concomitant symptom (704, 75.5 %), followed by rhinitis/sinusitis-related (350, 37.5 %) and respiratory symptoms (322, 34.5 %). Rhinitis/sinusitis-related symptoms more frequently occurred in patients with productive cough than in those with dry cough (49.0 % vs. 33.0 %, P

Abstract Ectomycorrhizal (ECM) symbiosis is an evolutionary biological trait of higher plants for effective nutrient uptakes. However, little is known that how the formation and morphological differentiations of ECM roots mediate the nutrients of below‐ and aboveground plant tissues and the balance among nutrient elements across environmental gradients. Here, we investigated the effects of ECM foraging strategies on root and foliar N and P concentrations and N:P ratio Abies faxoniana under variations of climate and soil conditions. The ECM symbionts preferentially mediated P uptake under both N and P limitations. The uptake efficiency of N and P was primarily associated with the ECM root traits, for example, ECM root tip density, superficial area of ECM root tips, and the ratio of living to dead root tips, and was affected by the ECM proliferations and morphological differentiations. The tissue N and P concentrations were positively associated with the abundance of the contact exploration type and negatively with that of the short‐distance exploration type. Our findings indicate that the nutritional status of both below‐ and aboveground plant tissues can be strongly affected by ECM symbiosis in natural environments. Variations in the ECM strategies in response to varying environmental conditions significantly influence plant nutrient uptakes and trade‐offs.

Arginine methylation mediated by protein arginine methyltransferases (PRMTs) has been shown to be an important posttranslational mechanism involved in various biological processes. Herein, we sought to investigate whether PRMT5, a major type II enzyme, is involved in pathological angiogenesis and, if so, to elucidate the molecular mechanism involved. Our results show that PRMT5 expression is significantly upregulated in ischemic tissues and hypoxic endothelial cells (ECs). Endothelial-specific Prmt5-KO mice were generated to define the role of PRMT5 in hindlimb ischemia–induced angiogenesis. We found that these mice exhibited impaired recovery of blood perfusion and motor function of the lower limbs, an impairment that was accompanied by decreased vascular density and increased necrosis as compared with their WT littermates. Furthermore, both pharmacological and genetic inhibition of PRMT5 significantly attenuated EC proliferation, migration, tube formation, and aortic ring sprouting. Mechanistically, we showed that inhibition of PRMT5 markedly attenuated hypoxia-induced factor 1-α (HIF-1α) protein stability and vascular endothelial growth factor–induced (VEGF-induced) signaling pathways in ECs. Our results provide compelling evidence demonstrating a crucial role of PRMT5 in hypoxia-induced angiogenesis and suggest that inhibition of PRMT5 may provide novel therapeutic strategies for the treatment of abnormal angiogenesis-related diseases, such as cancer and diabetic retinopathy.

Several studies have revealed that urban rivers with relatively complete habitat structures can support a high level of biodiversity in urban areas. However, few studies have analyzed the impact of the plan, design, and management of multi-scale urban riverside green space on bird communities by assessing several aspects of diversity (e.g., taxonomic and functional). In this study, we explored bird community variation (taxonomic and functional) among three rivers (28 sampling sites) with different levels of human disturbance along the urban development gradient in Kunming, Yunnan Province, China, during an annual cycle. This study related bird species richness and functional diversity to environmental variables at three spatial scales: landscape metrics at two different landscape scales (500 and 100 m radius) and vegetation structure at patch scales (20 m radius). Using partial least squares regression (PLSR) and multiple linear regression, we found that bird species richness and functional diversity were strongly related to various landscape- and patch-level variables. Multiple linear regression models revealed that, compared with the richness influenced by explanatory variables on three spatial scales (500, 100, and 20 m), the functional diversity was significantly influenced by explanatory variables on the 100 and 20 m scales. Tree cover at the 20 m scale had significantly positive impacts on bird species richness and functional diversity. Forest land in the 100 m scale had a significantly positive effect on bird species richness and functional diversity, while construction land in the two landscape scales (the 500- and 100 m scales) had a significantly negative effect on species richness. Accordingly, we suggest that urban riverside green space should be planned and managed at multiple scales.

To determine whether aorta becomes immune organ in pathologies, we performed transcriptomic analyses of six types of secretomic genes (SGs) in aorta and vascular cells and made the following findings: 1) 53.7% out of 21,306 human protein genes are classified into six secretomes, namely, canonical, caspase 1, caspase 4, exosome, Weibel–Palade body, and autophagy; 2) Atherosclerosis (AS), chronic kidney disease (CKD) and abdominal aortic aneurysm (AAA) modulate six secretomes in aortas; and Middle East Respiratory Syndrome Coronavirus (MERS-CoV, COVID-19 homologous) infected endothelial cells (ECs) and angiotensin-II (Ang-II) treated vascular smooth muscle cells (VSMCs) modulate six secretomes; 3) AS aortas upregulate T and B cell immune SGs; CKD aortas upregulate SGs for cardiac hypertrophy, and hepatic fibrosis; and AAA aorta upregulate SGs for neuromuscular signaling and protein catabolism; 4) Ang-II induced AAA, canonical, caspase 4, and exosome SGs have two expression peaks of high (day 7)-low (day 14)-high (day 28) patterns; 5) Elastase induced AAA aortas have more inflammatory/immune pathways than that of Ang-II induced AAA aortas; 6) Most disease-upregulated cytokines in aorta may be secreted via canonical and exosome secretomes; 7) Canonical and caspase 1 SGs play roles at early MERS-CoV infected ECs whereas caspase 4 and exosome SGs play roles in late/chronic phases; and the early upregulated canonical and caspase 1 SGs may function as drivers for trained immunity (innate immune memory); 8) Venous ECs from arteriovenous fistula (AVF) upregulate SGs in five secretomes; and 9) Increased some of 101 trained immunity genes and decreased trained tolerance regulator IRG1 participate in upregulations of SGs in atherosclerotic, Ang-II induced AAA and CKD aortas, and MERS-CoV infected ECs, but less in SGs upregulated in AVF ECs. IL-1 family cytokines, HIF1α, SET7 and mTOR, ROS regulators NRF2 and NOX2 partially regulate trained immunity genes; and NRF2 plays roles in downregulating SGs more than that of NOX2 in upregulating SGs. These results provide novel insights on the roles of aorta as immune organ in upregulating secretomes and driving immune and vascular cell differentiations in COVID-19, cardiovascular diseases, inflammations, transplantations, autoimmune diseases and cancers.

Abstract Background Global warming has brought many negative impacts on terrestrial ecosystems, which makes the vulnerability of ecosystems one of the hot issues in current ecological research. Here, we proposed an assessment method based on the IPCC definition of vulnerability. The exposure to future climate was characterized using a moisture index (MI) that integrates the effects of temperature and precipitation. Vegetation stability, defined as the proportion of intact natural vegetation that remains unchanged under changing climate, was used together with vegetation productivity trend to represent the sensitivity and adaptability of ecosystems. Using this method, we evaluated the vulnerability of ecosystems in Southwestern China under two future representative concentration pathways (RCP 4.5 and RCP 8.5) with MC2 dynamic global vegetation model. Results (1) Future (2017–2100) climate change will leave 7.4% (under RCP 4.5) and 57.4% of (under RCP 8.5) of areas under high or very high vulnerable climate exposure; (2) in terms of vegetation stability, nearly 45% of the study area will show high or very high vulnerability under both RCPs. Beside the impacts of human disturbance on natural vegetation coverage (vegetation intactness), climate change will cause obvious latitudinal movements in vegetation distribution, but the direction of movements under two RCPs were opposite due to the difference in water availability; (3) vegetation productivity in most areas will generally increase and remain a low vulnerability in the future; (4) an assessment based on the above three aspects together indicated that future climate change will generally have an adverse impact on all ecosystems in Southwestern China, with non-vulnerable areas account for only about 3% of the study area under both RCPs. However, compared with RCP 4.5, the areas with mid- and high-vulnerability under RCP 8.5 scenario increased by 13% and 16%, respectively. Conclusion Analyses of future climate exposure and projected vegetation distribution indicate widespread vulnerability of ecosystems in Southwestern China, while vegetation productivity in most areas will show an increasing trend to the end of twenty-first century. Based on new climate indicators and improved vulnerability assessment rules, our method provides an extra option for a more comprehensive evaluation of ecosystem vulnerability, and should be further tested at larger spatial scales in order to provide references for regional, or even global, ecosystem conservation works.

Abstract Background Chronic cough has an important impact on physical, social and psychological aspects. A simple and effective method to assess different aspects of chronic cough severity is required. We aimed to develop a simple, self-completed test, Cough Evaluation Test (CET), to evaluate cough severity and its impact on health. Method The items of preliminary CET were generated based on literature review and clinical practice. Items reduction was conducted by modified Delphi method. Patients with chronic cough were recruited to complete CET, Cough Visual Analog Scales (VAS), Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC), and Cough Symptom Score (CSS). Reassessments were performed at 1 week apart before treatment, and after more than 2 weeks treatments. Concurrent validation, internal consistency, repeatability, responsiveness and the minimal important difference (MID) were determined. Results CET consists of five items with a 5-point Likert scale (1–5 scaling of items, 5–25 score range). The Cronbach’s alpha values for CET was 0.80. CET showed a stronger correlation with LCQ-MC (r = − 0.74) compared to that between LCQ-MC with VAS (r = − 0.61). CET also showed a stronger correlation with VAS (r = 0.70) compared to that between VAS with other measures. Intraclass correlation coefficients for CET was 0.84. In patients undergoing treatment, CET scores significantly changed (p

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m6A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m6A-RMRs were more than downregulated m6A-RMRs in cancer types; five types of cancers upregulated ≥10 m6A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m6A-RMRs; (9) 86% of m6A-RMRs were differentially expressed in the six clusters of CD4+Foxp3+ immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m6A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m6A-RMRs, and inhibition of CD40 upregulated m6A-RMRs; (11) cytokines and interferons modulated m6A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m6A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m6A-RMRs; (14) m6A writer RBM15 and one m6A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m6A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m6A eraser FTO and two m6A writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated m6A-RMRs in 41 diseases and cancers, nine cellular and molecular mechanisms, novel therapeutic targets for inflammatory disorders, metabolic cardiovascular diseases, autoimmune diseases, organ failures, and cancers.

Background: Recurrent implantation failure (RIF) remains a critical and challenging problem in assisted reproductive technology mainly due to impaired decidualization. The endocytic and transcytotic activity in the endometrium are crucial for decidualization. The most representative endocytic gene is the C-terminal Eps15 homology domain-containing 1 (EHD1), but whether EHD1-mediated endocytic function is responsible for embryo implantation during decidualization remains unclear. Methods: A transcriptomic analysis was performed to evaluate the differentially expressed genes between the fertile control and RIF group. The expression and location of EHD1 in endometrial tissues were further examined by IHC, qRT-PCR and Western blotting. The transduction of an EHD1 recombinant adenovirus into human endometrial stromal cells was performed to investigate relevant decidualization marker genes. Additionally, a microarray analysis following the adenovirus-mediated overexpression of EHD1 was conducted to identify EHD1-related changes in HESCs, and the potential molecular mechanisms were further confirmed through immunofluorescence and coimmunoprecipitation analyses. Findings: An RNA-seq analysis demonstrated that EHD1 expression was significantly higher in the mid-secretory endometrium of the RIF group than in that of the fertile control group. The analysis of the menstrual cycle showed that expression of EHD1 increased in the mid-proliferative phase and showed a gradual decrease in the mid-secretory and decidual phases. Furthermore, EHD1 overexpression impaired decidualization by suppressing the expression of prolactin and insulin-like growth factor binding protein-1 and the formation of the cytoskeleton. The mechanistic analysis revealed the EHD1 regulated LRP5/6 protein function through the endocytic pathway, and subsequently suppressed the Wnt4/β-catenin pathway during decidualization. In addition, a Wnt4 agonist improved an impaired decidualization process. Interpretation: Regulation of the EHD1-Wnt4 pathway might serve as a promising therapeutic strategy for improving endometrial receptivity in RIF women. Keywords: EHD1, Decidualization, RIF, Wnt4

Vegetation is a key component of the terrestrial ecosystems, its dynamics serve as an indicator of vegetation health and ecosystem stability. However, the vegetation dynamics and its responses to climatic change and human activities remain unclear in southwestern China. The normalized difference vegetation index (NDVI) is widely used as a proxy of vegetation production. Here, a breakpoint method was used to better understand the vegetation trend dynamics based on the third generation Global Inventory Monitoring and Modeling System (GIMMS3g) NDVI in southwestern China. Meanwhile, a partial correlation analysis and residual trend (RESTREND) analysis were employed to detect the climatic and anthropogenic drivers behind vegetation dynamics. We found that the trend showed high heterogeneity in space. The annual mean NDVI generally increased at a rate of 0.0011 year−1 from 1982 to 2015, but much of the study area showed an opposite trend before and after the breakpoint. In the western part, the vegetation degraded with a reversal of trend from increase to decrease, where the vegetation types were mainly evergreen needle-leaved and grassland. In contrast, the vegetation increased significantly in the eastern part, showing greening trend regardless of browning or greening trend before the breakpoint. Temperature had a positive correlation with vegetation in the eastern part of the study area, while also had some negative correlations with vegetation in western mountainous areas where surface soils are prone to droughts. Solar radiation had a positive correlation with vegetation in the western part of the study area. Overall, temperature was the dominant climatic factor, and intensified human activities of afforestation and agriculture activities leaded to the strong greening trend. Our findings improved the understanding of long-term changes in vegetation and the roles of climate and anthropogenic activities over southwestern China.

To determine whether pro-inflammatory lipid lysophosphatidylinositols (LPIs) upregulate the expressions of membrane proteins for adhesion/signaling and secretory proteins in human aortic endothelial cell (HAEC) activation, we developed an EC biology knowledge-based transcriptomic formula to profile RNA-Seq data panoramically. We made the following primary findings: first, G protein-coupled receptor 55 (GPR55), the LPI receptor, is expressed in the endothelium of both human and mouse aortas, and is significantly upregulated in hyperlipidemia; second, LPIs upregulate 43 clusters of differentiation (CD) in HAECs, promoting EC activation, innate immune trans-differentiation, and immune/inflammatory responses; 72.1% of LPI-upregulated CDs are not induced in influenza virus-, MERS-CoV virus- and herpes virus-infected human endothelial cells, which hinted the specificity of LPIs in HAEC activation; third, LPIs upregulate six types of 640 secretomic genes (SGs), namely, 216 canonical SGs, 60 caspase-1-gasdermin D (GSDMD) SGs, 117 caspase-4/11-GSDMD SGs, 40 exosome SGs, 179 Human Protein Atlas (HPA)-cytokines, and 28 HPA-chemokines, which make HAECs a large secretory organ for inflammation/immune responses and other functions; fourth, LPIs activate transcriptomic remodeling by upregulating 172 transcription factors (TFs), namely, pro-inflammatory factors NR4A3, FOS, KLF3, and HIF1A; fifth, LPIs upregulate 152 nuclear DNA-encoded mitochondrial (mitoCarta) genes, which alter mitochondrial mechanisms and functions, such as mitochondrial organization, respiration, translation, and transport; sixth, LPIs activate reactive oxygen species (ROS) mechanism by upregulating 18 ROS regulators; finally, utilizing the Cytoscape software, we found that three mechanisms, namely, LPI-upregulated TFs, mitoCarta genes, and ROS regulators, are integrated to promote HAEC activation. Our results provide novel insights into aortic EC activation, formulate an EC biology knowledge-based transcriptomic profile strategy, and identify new targets for the development of therapeutics for cardiovascular diseases, inflammatory conditions, immune diseases, organ transplantation, aging, and cancers.

Processing texture on contact surfaces can improve the friction performance of mechanical comments. In this research, micro-dimple textures with various parameter were processed on a steel ball’s surface with a picosecond laser. Then, the EHL (elastohydrodynamic lubrication) oil film thickness was measured on an optical ball-on-disc tribometer subjected to pure sliding conditions. The effects of sliding velocity, load, dimple location and dimple depth on the film thickness were analyzed. The results showed that the dimple affected the pressure distribution in the contact area, which in turn changed the distribution of the local film thickness. An increase in the local film thickness occurred between the dimple and outlet of the contact region, while a decrease in the film thickness formed from the dimple to the entrance of the contact area and both sides of the dimple’s edge. Velocity and applied loads affected the film thickness distribution as well. As the sliding velocity increased, the film thickness increasing region enlarged, while the film thickness-decreasing area shrank. The increase in load resulted in a negative effect on the increase in film thickness. This study will provide a reference for point-contact designs with low friction conditions.

Oxidative stress damage is known as one of the important factors that induce neuropathic pain (NP). Using antioxidant therapy usually achieves an obvious curative effect and alleviates NP. Previous pharmacological studies have shown that higenamine (Hig) performs to be antioxidant and anti-inflammatory. However, the protective effect and mechanism of Hig on NP are still unclear. This study mainly evaluated the changes in reactive oxygen species (ROS) level, lipid peroxidation, and antioxidant system composed of superoxide dismutase (SOD) and glutathione (GSH) through chronic constrict injury (CCI) model rats and t-BHP-induced Schwann cell (SC) oxidative stress model. The expressions of two inflammatory factors, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were also assessed. The possible molecular mechanism of Hig in the treatment of NP was explored in conjunction with the expression of mitochondrial apoptosis pathway and NOX2/ROS/TRP/P38 mitogen-activated protein kinase (MAPK)/NF-ĸB pathway-related indicators. Hig showed substantial antioxidant and anti-inflammatory properties both in vivo and in vitro. Hig significantly reduced the upregulated levels of ROS, malondialdehyde (MDA), TNF-α, and IL-6 and increased the levels of SOD and GSH, which rebalanced the redox system and improved the survival rate of cells. In the animal behavioral test, it was also observed that Hig relieved the CCI-induced pain, indicating that Hig had a pain relief effect. Our research results suggested that Hig improved NP-induced oxidative stress injury, inflammation, and apoptosis, and this neuroprotective effect may be related to the NOX2/ROS/TRP/P38 MAPK/NF-ĸB signaling pathway.

To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum–MT, MT fusion, autophagosome–lysosome fusion, and autophagosome/endosome–lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome–lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)–MT contact, ER– plasma membrane (PM) junction, autophagosome/endosome–lysosome fusion, sarcoplasmic reticulum–MT, autophagosome–endosome/lysosome fusion, and ER–Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4+CD25− T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers.

Abstract Background Forests are increasingly valued for non-timber ecosystem services in place of conventional wood fiber production. Biomass carbon sequestration is one of the key ecosystem services forests are relied upon for mitigating global climate change. However, planning for large-scale tree planting and managing established forest stands for carbon sequestration require careful consideration of the gain in biomass production and tradeoff for other regulatory services. How a tradeoff between forest production and conservation of water resources is shaped by the condition of forest stand and environmental factors remains a question of broad interest in sustainable forest ecosystem management. Methods We studied the spatiotemporal patterns of net primary productivity (NPP), evapotranspiration (ET), and water use efficiency (WUE), and their relationships with local climatic and forest stand factors over a temperate forest landscape in Changbai Mountain, Northeast China. The time series of spatial data on NPP and ET were extracted from the global remote sensing datasets for the MOD16A3 and MOD17A3 products for the period 2000–2014. The time series of spatial patterns of annual precipitation and annual mean temperature were obtained as grid maps for regional meteorological variables. Stand patches were categorized into the types of conifers, broadleaves, and mixed-wood, as well as age-classes of young, mid-age, near mature, mature, and old-growth stands, and by establishment into natural and planted. Information on stands and selective site variables were compiled from the Forest Inventory Datasets of China. Analyses were performed with Arc-GIS. Results Over the study period of 2000–2014, the landscape-level annual NPP varied between 311.7 and 573.6 gC∙m− 2∙a− 1, ET between 559.9 and 603.0 mm∙a− 1, and WUE between 0.54 and 1.01 gC∙m− 2∙mm− 1. Across the forest landscape, the mean annual NPP varied between 205.0 and 639.4 gC∙m− 2∙a− 1, ET between 441.5 and 784.0 mm∙a− 1, and WUE in the range of 0.46–1.10 gC∙m− 2∙mm− 1. The spatial variations in NPP, ET, and WUE were commonly attributable to forest type, stand age class and density, establishment mode, and temperature variables, with some effects of other selective factors on ET and WUE. The three forest types were significantly (p

Abstract Background Soil organic carbon (SOC) is a large reservoir of terrestrial carbon (C); it consists of different fractions of varying complexity and stability. Partitioning SOC into different pools of decomposability help better predict the trend of changes in SOC dynamics under climate change. Information on how physical fractions and chemical structures of SOC are related to climate and vegetation types is essential for spatial modelling of SOC processes and responses to global change factors. Method Soil samples were collected from multiple representative forest sites of three contrasting climatic zones (i.e. cool temperate, warm temperate, and subtropical) in eastern China. Measurements were made on SOC contents and physical fractions of the 0–20 cm soil layer, and the chemical composition of SOC of the 0–5 cm soil layer, along with measurements and compilation of the basic site and forest stand variables. The long-term effects of temperature, litter inputs, soil characteristics and vegetation type on the SOC contents and factions were examined by means of “space for time substitution” approach and statistical analysis. Result Mean annual temperature (MAT) varied from 2.1 °C at the cool temperate sites to 20.8 °C at the subtropical sites. Total SOC of the 0–20 cm soil layer decreased with increasing MAT, ranging from 89.2 g·kg− 1 in cool temperate forests to 57.7 g·kg− 1 in subtropical forests, at an average rate of 1.87% reduction in SOC with a 1 °C increase in MAT. With increasing MAT, the proportions of aromatic C and phenolic C displayed a tendency of decreases, whereas the proportion of alkyl C and A/O-A value (the ratio of alkyl C to the sum of O-alkyl C and acetal C) displayed a tendency of increases. Overall, there were no significant changes with MAT and forest type in either the physical fractions or the chemical composition. Based on the relationship between the SOC content and MAT, we estimate that SOC in the top 20 soil layer of forests potentially contribute 6.58–26.3 Pg C globally to the atmosphere if global MAT increases by 1 °C–4 °C by the end of the twenty-first century, with nearly half of which (cf. 2.87–11.5 Pg C) occurring in the 0–5 cm mineral soils. Conclusion Forest topsoil SOC content decreased and became chemically more recalcitrant with increasing MAT, without apparent changes in the physical fractions of SOC.