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Cancer‐associated fibroblasts (CAF) are the most abundant stromal cells in tumor and exert a pro‐tumoral effect in cancer progression. Numerous evidence shows long non‐coding RNA (lncRNA) abnormally regulates gene expression in various cancers. However, little is known about the role of lncRNA in the interaction between CAF and cancer cells. Here, we first identify an uncharacterized lncRNA, LOC100506114, which is significantly upregulated in CAF and is involved in the functional transformation of normal fibroblasts (NF) and CAF. Expression of LOC100506114 enhances the expression of fibroblast activation protein alpha and α‐smooth muscle actin in NF and promotes malignant characteristics of NF and CAF in vivo and in vitro. The profile of gene co‐expression analysis shows that growth differentiation factor 10 (GDF10) is positively correlated with the expression of LOC100506114. CAF promote stromal fibroblast activation and the proliferation and migration of tumor cells by secreting GDF10. Our data demonstrate that lncRNA plays a critical role in the interplay of stromal fibroblasts and tumor cells in oral squamous cell carcinoma., Abnormal expression of lncRNA LOC100506114 in oral squamous cell carcinoma (OSCC) induced normal fibroblasts (NF) to transform into CAF by upregulating growth differentiation factor 10 (GDF10) expression and secretion. The interaction of GDF10 with the transcription factor RUNX family transcription factor 2 further enhanced the growth and migration of OSCC tumor cells by activating the TGFβRI/Smad3/ERK pathway. Our results demonstrate that lncRNA play an important role in the functional transformation of human NF into CAF and promote OSCC tumorigenesis.

We investigate how state-owned corporate venture capital differs from privately owned corporate venture capital in fostering innovation among startups. Based on the data of Chinese A-share listed companies and the startups in their portfolios that they invested in between 2009 and 2018, we find that startups backed by state-owned corporate venture capital are less innovative than startups backed by privately owned corporate venture capital. Using a two-stage least-squares analysis yields the same results. Further, we find evidence consistent with two potential mechanisms: Investors of state-owned corporate venture capital provide weaker technical support and are less tolerant of failure. These results have important implications for stakeholders, management, and policy makers who care about incentivizing young and rapidly growing companies to innovate more effectively.

Major depressive disorder (MDD) is a neurasthenic disease, which is the second-largest burden of disease globally. Increasing studies have revealed that depression is associated with abnormalities in gut microbiota and metabolites. Several species of bacteria have been classified as psychobiotics, which confer mental health benefits through interactions with commensal gut microbiota. Therefore, it is essential to identify new psychobiotics and elucidate their mechanisms in the treatment of depression. This study aims to evaluate the antidepressant effect of Akkermansia muciniphila (AKK) in a mouse model of depression induced by chronic restraint stress (CRS). C57BL/6 male mice were divided into three groups: mice subjected to CRS, mice not subjected to CRS, and mice treated with AKK for 3 weeks. Behavioral tests were performed, and hormone, neurotransmitter, and brain-derived neurotrophic factor (BDNF) levels were measured. Cecal microbiota was analyzed using 16S rRNA gene sequencing, and serum metabolites were detected using untargeted metabolomics. In addition, correlations between altered gut microbiota and metabolites with significant variations in serum associated with AKK ameliorating depression were analyzed using Pearson’s correlation coefficient. The results revealed that AKK significantly ameliorated depressive-like behavior and restored abnormal variations in depression-related molecular (corticosterone, dopamine, and BDNF). Moreover, AKK altered chronic stress–induced gut microbial abnormalities. Untargeted metabolomics analysis revealed 23 potential biomarkers in serum that could be associated with the mechanisms underlying CRS-induced depression and the therapeutic effects of AKK. Pearson’s correlation coefficient analysis revealed that AKK predominantly upregulated β-alanyl-3-methyl-l-histidine and edaravone to relieve depression. Furthermore, β-alanyl-3-methyl-l-histidine and edaravone exhibited the antidepressant phenotype in mice subjected to CRS. In conclusion, the study demonstrated that AKK ameliorates chronic stress–induced depressive symptoms in mice by regulating gut microbiota and metabolites. • AKK reduces depressive-like behaviors induced by chronic stress. • AKK regulates the gut microbial structure and metabolomics of serum under the chronic stress. • Antidepressant effect of AKK correlates with the increase of β-alanyl-3-methyl-l-histidine and edaravone.

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Myeloid-derived suppressor cells (MDSCs) have been found to be involved in the regulation of SLE development. However, little is known about the association between MDSC subsets and the factors that draw MDSCs into abnormal expansion. This study found that the percentage of M-MDSCs increased in mice with pristane-induced lupus. Toll-like receptor (TLR)7 signal activation and high interferon-α (IFN-α) level promoted M-MDSC differentiation in vitro. Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-α-induced bone marrow (BM) differentiation into MDSCs in vitro. In terms of mechanism, whole-genome transcriptome profiling was performed by RNA sequencing, revealing that the expression of the transcription factor IRF-8 was higher in M-MDSCs isolated from pristane-induced lupus mice, compared with control mice. IRF-8 was identified to be crucial for TLR7- and IFN-α-induced BM differentiation into MDSCs in vitro. Furthermore, interferon (IFN) regulatory factor8 (IRF-8) was targeted by miR-451a in M-MDSC differentiation. Of note, metformin-modified M-MDSCs could relieve lupus symptoms in pristane-induced lupus mice. The findings revealed a novel mechanism linking IRF-8/miR-451a to M-MDSC differentiation via the AMPK/mTOR signal pathway during lupus development. This study might provide an important reference for SLE therapy by targeting M-MDSCs.

Drylands cover about one-half of the land surface in China and are highly sensitive to climate change. Understanding climate change and its impact drivers on dryland is essential for supporting dryland planning and sustainable development. Using meteorological observations for 1960–2019, the aridity changes in drylands of China were evaluated using aridity index (AI), and the impact of various climatic factors [i.e., precipitation P; sunshine duration (SSD); relative humidity (RH); maximum temperature (Tmax); minimum temperature (Tmin); wind speed (WS)] on the aridity changes was decomposed and quantified. Results of trend analysis based on Sen’s slope estimator and Mann–Kendall test indicated that the aridity trends were very weak when averaged over the whole drylands in China during 1960–2019 but exhibited a significant wetting trend in hyperarid and arid regions of drylands. The AI was most sensitive to changes in water factors (i.e., P and RH), followed by SSD, Tmax, and WS, but the sensitivity of AI to Tmin was very small and negligible. Interestingly, the dominant climatic driver to AI change varied in the four dryland subtypes. The significantly increased P dominated the increase in AI in the hyperarid and arid regions. The significantly reduced WS and the significantly increased Tmax contributed more to AI changes than the P in the semiarid and dry subhumid regions of drylands. Previous studies emphasized the impact of precipitation and temperature on the global or regional dry–wet changes; however, the findings of this study suggest that, beyond precipitation and temperature, the impact of wind speed on aridity changes of drylands in China should be given equal attention.

A method of the scattering Phase Function Scaling (PFS) for determination of the direct normal irradiance (DNI) involving the circumsolar normal irradiance (CSNI) is developed. A fraction of the normalized phase function integrated over the field of view for a pyrheliometer is introduced in the radiative transfer equation so the scaled optical depth using this phase function is derived. The PFS method is tested in a radiative transfer scheme and a simple fast parametric scheme SUNFLUX using the observational datasets at 14 Baseline Surface Radiation Network (BSRN) stations. The evaluation results show that the modelled DNI in terms of the PFS method in the radiative transfer scheme is significantly improved compared with that using the original delta-Eddington scaling method and compared well with that determined using other two radiative transfer models of DISORT and SMARTS. The modelled DNI with the PFS method in the SUNFLUX scheme is also improved compared with that without using the PFS method and compared well with that from the SMARTS model. The CSNI is also evaluated against the results from the other three models. The results are generally poor in all cases. The poor results are mainly due to the small magnitude of CSNI and uncertainties in the input data. Uncertainty in the aerosol scattering phase function could be the main reason responsible for the poor comparisons.

A new aerosol direct transmittance parameterization is developed based on detailed radiative transfer model calculations for improving direct normal irradiance (DNI) for the solar energy forecast in the fast radiation scheme SUNFLUX. The modified SUNFLUX scheme is evaluated against observational datasets collected from the 14 Baseline Surface Radiation Network (BSRN) stations. The aerosol data from AERONET stations collocated with the BSRN network are used in the evaluations. The evaluation results have indicated that the accuracy of the calculated DNI using the new version of SUNFLUX has been improved significantly compared to the old version. The relative mean bias difference (MBD) and relative root mean square difference (RMSD) are −3.03% and 4.95%, respectively. The performance of the modified DNI model is also compared with those from the other five models. The results predicted by the current model are comparable with those from the best reference models. More importantly, the evaluation results show that the new aerosol scheme developed in this study can also be applied to other models to improve their performance.

Taking Zibo Dawu Water Source Area as the research area, with the help of MapGIS and SPSS analysis tools, the health risks Make an evaluation. The results showed that As, Pb, and Ni belonged to the risk-free level, Hg reached a high-risk level, and Cd reached a medium risk level. The source of Cr is similar to Ni, Cd, Pb, As, the source of Ni is similar to Cd, Pb, and the source of Pb is similar to Hg. The comprehensive non-carcinogenic risk indexes of heavy metals for adults and children are 7.94E-03 and 3.38E-03, respectively, and there is no non-carcinogenic risk; the total carcinogenic risk indexes of heavy metals for adults and children are 5.52E-06 and 4.23E-06, respectively , There is a carcinogenic risk that the human body can bear, and the main influencing factors are Ni and Cr. Skin contact is the main way for heavy metals to cause health risks.

Background: Warfarin, along with aspirin and clopidogrel, has long been recommended for patients with atrial fibrillation (AF) who are undergoing percutaneous coronary intervention with a drug-eluting stent (PCI-DES). However, this triple therapy has been known to increase the risk of bleeding complications. Meanwhile, there is no evidence from prospective trials on the use of ticagrelor in a dual therapy. We here aimed to compare the antiplatelet drug ticagrelor as a dual antithrombotic agent to aspirin and clopidogrel in bleeding events.Methods: In this multicenter, active-controlled, open-label, randomized trial, patients with AF taking warfarin who had undergone PCI-DES were randomly assigned to the ticagrelor therapy group (Dual group) or the clopidogrel plus aspirin therapy group (Triple group). The primary and secondary endpoints were overall bleeding events and major bleeding events, respectively, according to the Thrombolysis in Myocardial Infarction (TIMI) criteria at 6 months. Cardiovascular events [re-PCI, surgical bypass, myocardial infarction (MI), heart failure, rehospitalization due to angina pectoris, stent thrombosis and death due to cardiovascular causes] at 6 months were also recorded.Results: A total of 296 patients from 12 medical centers in China were randomized after PCI-DES to either the Dual therapy group (n = 148) or the Triple group (n = 146) for 6 months. The overall incidence of bleeding events at 6 months was 36.49% in the Dual therapy group and 35.62% in the Triple group [hazard ratio, 0.930; 95% confidence interval (CI), 0.635 to 1.361; P = 0.7088]. The incidence of the secondary endpoint over 6 months was 4.73% in the Dual therapy group and 1.37% in the Triple group (hazard ratio, 0.273; 95% CI, 0.057 to 1.315; P = 0.1056). Cardiovascular event occurrence was also comparable in both groups at 6 months (18.24 vs. 16.44%; hazard ratio, 0.845; 95% CI, 0.488 to 1.465; P = 0.5484).Conclusions: The incidence of total bleeding events in AF patients treated with ticagrelor was comparable to that in patients treated with clopidogrel plus aspirin at 6 month; Meanwhile, the incidence of cardiovascular events were also comparable between the groups.Clinical Trial Registration: MANJUSRI, ClinicalTrials.gov# NCT02206815, 2014, August 1st

Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.

Colorectal cancer (CRC) is the third most common type of cancer. Here, we studied the inhibitory effect of IRAK1 and IRAK4 as a preventive strategy using a colitis-induced tumorigenesis mouse model. CRC clinical data were obtained from the Gene Expression Omnibus (GEO). An experimental inflammation-dependent CRC model was induced by treatment with azoxymethane (AOM) and then dextran sodium sulfate (DSS) in C57BL/6 mice. Mice were administered an IRAK1/4 inhibitor by intraperitoneal injection at 3 mg/kg twice each week for 9 weeks. The IRAK1/4 inhibitor attenuated histological changes and prevented tumor growth. Tumor-associated proteins, including p65 and Ki-67, were downregulated by the IRAK1/4 inhibitor in AOM/DSS-treated mice. Additionally, IRAK1/4 inhibitor administration effectively decreased the expression of inflammatory cytokines. Furthermore, we observed that IRAK1/4 inhibitor treatment attenuated colitis-induced tumorigenesis by inhibiting epithelial-mesenchymal transition. These observations indicate that inhibition of IRAK1 and IRAK4 may suppress experimental colitis-induced tumorigenesis by inhibiting inflammatory responses and epithelial-mesenchymal transition.

Purpose Total flavone of Abelmoschus manihot (TFA), the effective constituents extracted from Flos Abelmoschus Manihot, has been reported to inhibit inflammation. However, the effect of TFA on ulcerative colitis (UC) progression in patients with depression is unknown. The purpose of our research was to explore the anti-UC effects of TFA in the context of depression in mice with UC by regulating the gut microbiota to drive the intestinal barrier. Methods In this study, chronic stress (CS) and dextran sodium sulfate (DSS) were used to induce depression and UC, respectively, in C57BL/6J mice. Fecal microbiota transplantation (FMT) was used to evaluate how treating mice modeling UC and depression with TFA effected their gut microbiota. Results Our results showed that TFA effectively improved UC aggravated by CS. In addition, TFA treatment improved the depression-like phenotype, the disturbed gut microbiota, and the intestinal barrier function in CS mice. It is worth noting that FMT from the CS mice to the receptor group further aggravated the damage of the intestinal barrier and the disturbance of the gut microbiota in the recipient DSS mice, thus further aggravating UC, however, treatment of the intervention of TFA in the CS fecal microbiota transplant with TFA also played its therapeutic outcome. Conclusion Taken together, our results show that CS disrupts the gut microbiota, triggers intestinal barrier injury and aggravates DSS colitis, while TFA is a promising drug for the treatment of UC in patients with depression., Graphical Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by systemic chronic inflammation that can affect multiple major organ systems. Although the etiology of SLE is known to involve a variety of factors such as the environment, random factors and genetic susceptibility, the exact role of CD11b+Gr1+ myeloid cells in lupus progression is not fully understood. Myeloid-derived CD11b+Gr1+ cells are thought to be a heterogeneous group of immature myeloid cells with immune function. Some studies have reported that CD11b+Gr1+ cells and the activation of mTOR pathway are involved in the pathogenesis of systemic lupus erythematosus (SLE). However, it is still not clarified about the mechanism of influence of lupus microenvironment and mTOR signaling on CD11b+Gr1+ cells. In the present study, we found that the percentage of CD11b+Gr1+ cells increased prior to the abnormal changes of Th17, Treg, T and B cells during lupus development. TLR7 and IFN-α signaling synergized to promote CD11b+Gr1+ cell accumulation in an mTOR-dependent manner. Moreover, compared to a traditional mTOR inhibitor, INK128 inhibited more effectively the disease activity via regulating CD11b+Gr1+ cell expansion and functions. Furthermore, TLR7/IFN-α-modified CD11b+Gr1+ cells promoted unbalance of Th17/Tregs and were inclined to differentiate into macrophages via the mTOR pathway. In conclusion, CD11b+Gr1+ cells increased in the early stages of the lupus progression and mTOR pathway was critical for CD11b+Gr1+ cells in lupus development, suggesting the changes of inflammation-induced CD11b+Gr1+ cells initate lupus development. We also provide evidence for the first time that INK128, a second generation mTOR inhibitor, has a good therapeutic action on lupus development by regulating CD11b+Gr1+ cells.

The total flavone of Abelmoschus manihot (TFA), a compound extracted from the flowers of Abelmoschus manihot (L.) Medic, has been widely used for the treatment of Crohn's disease, chronic glomerulonephritis and other diseases. The aim of this study was to investigate the effect of TFA on gut microbiota and intestinal barrier in dextran sulfate sodium (DSS) induced experimental colitis. C57BL/6J mice were treated with 2.5% DSS in drinking water to induce colitis. Mice were orally administrated with TFA (62.5mg/kg, 125mg/kg) or prednisone acetate (PAT, 2.5mg/kg) once daily for 7 days. Biological samples were collected for analysis of inflammation cytokines, gut microbiota and intestinal barrier integrity. TFA-H (125mg/kg) markedly attenuated DSS-induced colon shortening and histological injury in experimental colitis. The therapeutic effect was similar with PAT administration. TFA-H notably modulated the dysbiosis of gut microbiota induced by DSS and greatly enriched the Akkermansia muciniphila (A. muciniphila). Moreover, TFA-H remarkably ameliorated colonic inflammatory response and intestinal epithelial barrier dysfunction. Interestingly, TFA directly promotes the growth of A. muciniphila in vitro. Taken together, the results for the first time revealed that TFA, as a prebiotic of A. muciniphila, improved DSS-induced experimental colitis, at least partly through modulating gut microflora profile to maintain the colonic integrity and inhibit inflammation response.

The total flavone of Abelmoschus manihot (TFA), a compound extracted from the flowers of Abelmoschus manihot (L.) Medic, has been widely used for the treatment of Crohn's disease, chronic glomerulonephritis and other diseases. The aim of this study was to investigate the effect of TFA on the gut microbiota and intestinal barrier in dextran sulfate sodium (DSS)-induced experimental colitis. C57BL/6J mice were treated with 2.5% DSS in drinking water to induce colitis. Mice were orally administered TFA (62.5 mg/kg, 125 mg/kg) or prednisone acetate (PAT, 2.5 mg/kg) once daily for 7 days. Biological samples were collected for analysis of inflammatory cytokines, gut microbiota and intestinal barrier integrity. TFA-H (125 mg/kg) markedly attenuated DSS-induced colon shortening and histological injury in experimental colitis. The therapeutic effect was similar to that of PAT administration. TFA-H notably modulated the dysbiosis of gut microbiota induced by DSS and greatly enriched Akkermansia muciniphila (A. muciniphila). Moreover, TFA-H remarkably ameliorated the colonic inflammatory response and intestinal epithelial barrier dysfunction. Interestingly, TFA directly promotes the growth of A. muciniphila in vitro. Taken together, the results revealed for the first time that TFA, as a prebiotic of A. muciniphila, improved DSS-induced experimental colitis, at least partly by modulating the gut microflora profile to maintain colonic integrity and inhibit the inflammatory response.

Incorporation of microbiome data has recently become important for prevention, diagnosis, and treatment of colorectal cancer, and several species of bacteria were shown to be associated with carcinogenesis. However, the role of commensal fungi in colon cancer remains poorly understood. Here, we report that mice lacking the c-type lectin Dectin-3 (Dectin-3-/- ) show increased tumorigenesis and Candida albicans burden upon chemical induction. Elevated C. albicans load triggered glycolysis in macrophages and interleukin-7 (IL-7) secretion. IL-7 induced IL-22 production in RORγt+ (group 3) innate lymphoid cells (ILC3s) via aryl hydrocarbon receptor and STAT3. Consistently, IL-22 frequency in tumor tissues of colon cancer patients positively correlated with fungal burden, indicating the relevance of this regulatory axis in human disease. These results establish a C. albicans-driven crosstalk between macrophages and innate lymphoid cells in the intestine and expand our understanding on how commensal mycobiota regulate host immunity and promote tumorigenesis.

Major depressive disorder (MDD) is a neurasthenic disease, which is the second-largest burden of disease globally. Increasing studies have revealed that depression is associated with abnormalities in gut microbiota and metabolites. Several species of bacteria have been classified as psychobiotics, which confer mental health benefits through interactions with commensal gut microbiota. Therefore, it is essential to identify new psychobiotics and elucidate their mechanisms in the the treatment of depression. This study aims to evaluate the antidepressant effect of Akkermansia muciniphila (AKK) in a mouse model of depression induced by chronic restraint stress (CRS). C57BL/6 male mice were divided into three groups: mice subjected to CRS, mice not subjected to CRS, and mice treated with AKK for three weeks. Behavioral tests were performed, and hormone, neurotransmitter, and brain-derived neurotrophic factor (BDNF) levels were measured. Cecal microbiota was analyzed using 16S rRNA gene sequencing, and serum metabolites were detected using untargeted metabolomics. In addition, correlations between altered gut microbiota and metabolites with significant variations in serum associated with AKK ameliorating depression were analyzed using Pearson’s Correlation coefficient. The results revealed that AKK significantly ameliorated depressive-like behavior and restored abnormal variations in depression related molecular (corticosterone, dopamine and BDNF). Moreover, AKK altered chronic stress-induced gut microbial abnormalities. Untargeted metabolomics analysis revealed 23 potential biomarkers in serum that could be associated with the mechanisms underlying CRS-induced depression and the therapeutic effects of AKK. Pearson's correlation coefficient analysis revealed that AKK predominantly upregulated β-Alanyl-3-methyl-L-histidine and edaravone to relieve depression. Furthermore, β-Alanyl-3-methyl-L-histidine and edaravone exhibited the antidepressant phenotype in mice subjected to CRS. In conclusion, the study demonstrated that AKK ameliorates chronic stress-induced depressive symptoms in mice by regulating gut microbiota and metabolites. Funding Statement: This work was supported by the National Natural Science Foundation of China (No. 81873309). Declaration of Interests: There are no conflicts of interest to declare. Ethics Approval Statement: The experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of the Nanjing University of Chinese Medicine.

Background:Ulcerative colitis (UC) patients have a high incidence of mental disorders. The microbiota-gut-brain axis dysfunction is considered as one important pathogenesis of mental diseases. At present, little is known about how gut microbiota interact with the host in UC patients with depression and anxiety.Results: This prospective observational study enrolled 240 Chinese patients in two cohorts: the discovery cohort, including 69 active UC patients, 49 non-inflammatory bowel disease (IBD) depression and anxiety patients, and 62 healthy people, and the replication cohort of 60 active UC patients. About half of active UC patients showed symptoms of depression or anxiety. Through 16s rRNA sequencing, it was found that these UC patients accompanied with depression and anxiety had lower fecal microbial abundance with more Sellimonas , Eubacterium ventriosum group , Enterococcus , and Peptoclostridium , but less Prevotella_9 , Erysipelotrichaceae UCG_003 , Collinsella , and Dorea , compared with non-depressed/ anxious UC patients. Serum metabolome and proteome analysed using liquid chromatography/ mass spectrometry showed significantly increased glycochenodeoxycholate, stearoyllysophosphatidylcholine, and glyceryl stearates, while decreased 2'-deoxy-D-ribose and a set of immunoglobulin protein in the serum of UC patients with depression and anxiety. Through integration of multiple statistical analyses and multi-omics correlation analyses, we revealed a highly connected and comprehensive network, centring on Prevotella_9 and 1-stearoyl-sn-glycerol, composed of these bacteria, metabolites and proteins associated with UC-specific depression and anxiety.Conclusion: This study has identified a highly connected multi-omics network, composed of a set of gut microbiota, serum metabolites and proteins, specifically related to depression and anxiety in active UC. This network might influence host's mental state through mediating the effect of gut inflammation on synapse pruning in the central nervous system.

The agricultural activities, hydrologic cycle, and ecological environment are seriously influenced by evapotranspiration (ET), especially in arid and semi-arid areas. A new method for estimating daily global solar radiation (GSR) over rugged terrains in the middle Heihe River Basin is developed on the basis of Iqbal model C. And with the land surface parameters retrieved from multisource remote sensing data, a daily surface ET on June 21–24, 2009, is simulated by using surface energy balance algorithm for land (SEBAL) model. The results show: 1. An improved daily GSR with a resolution of 100 m × 100 m is implemented. The mean absolute bias error (MABE) is 9 W/m2, and the mean absolute relative bias error (MARBE) is 2.5 %. The MABE of the daily GSR using the SEBAL model is 122.2 W/m2, and the MARBE is 33.9 %. 2. The spatial distribution of the daily GSR is more reasonable using the improved model than the original model. The GSR is larger on a sunny slope (an open place) than on a shady slope (a rugged place). 3. Bringing the new model into SEBAL significantly improves the accuracy of the ET. The MABE of ET decreases from 2.1 mm (original scheme) to 0.6 mm (improved scheme), and the MARBE declines from 44 % to 13 % accordingly. Moreover, the spatiotemporal resolution of the ET simulation is effectively improved by the combined moderate-resolution imaging spectroradiometer and thematic mapper surface parameters. 4. All highest ET value appeared in all types of water bodies, followed by farmland, forest, wetland, and residential areas, the lowest values appeared over bare rock land. The water consumption in these areas is dominated by agriculture. The new results provide better theoretical basis and scientific guidance for ecosystem protection and sustainable utilization of water resources.

There are trillions and trillions of microorganisms in the human gut, and these microorganisms and their metabolites are closely related to human health. Recent studies have found that the abundance of Akkermansia muciniphila is decreased in many diseases. Supplementation of A. muciniphila is used to treat many diseases, suggesting it as a probiotic. Herbal medicines are considered as valuable asset of traditional Chinese medicine. Recent studies have revealed traditional Chinese medicine as a potential prebiotic agent for the treatment of many diseases. Hence, in this review, we aimed to provide a plausible mechanistic basis for the interactions between herbal medicines and A. muciniphila, and therapeutic benefits on this interaction in various illnesses.

Accumulated temperature is an important index in agricultural heat resources and is composed of lasting days and the average temperature of its lasting days by definition. This study compared and analyzed the spatiotemporal changes of the ≥ 10 °C accumulated temperature (AT10), the lasting days of AT10 (N) and the average temperature of the lasting days ( $$ \overline{T} $$ ), and later quantitatively evaluated the dominant factor causing the variation of AT10 based on the daily meteorological observation data from 755 stations from 1961 to 2010 in China. We detected that AT10, N and $$ \overline{T} $$ showed notable increasing trends with an average of 59.18 °C·d/10a, 2.08 d/10a and 0.11 °C/10a, respectively, from 1961 to 2010 in China. The spatial shift of the ≥10 °C accumulated temperature zones (ATZs) was affected by both lasting days zones (LDZs) and the average temperature zones (TZs), but the northern shift of ATZs was more affected by the northern shift of LDZs. Our results also showed that there were regional differences in the dominant factor related to the variation of AT10 in China. There were 62.1% stations where the variation of AT10 was dominated by N, and 14.3% of stations were dominated by $$ \overline{T} $$ . We divided the variation of AT10 into six types based on N and $$ \overline{T} $$ in China, and different corresponding measures should be taken for different AT10 change types in response to the effects of climate warming on agricultural production.

Myeloid-derived suppressor cells (MDSCs) can regulate various aspects of immune responses based on their potent immune-suppressive activity. Studies reported that MDSCs participated in many autoimmune diseases. However, the role of MDSCs in Sjögren's syndrome (SS) is unknown. In this study, we determined the frequencies and function of MDSCs in non-obese diabetic (NOD) mice and SS patients. The NOD mice were adoptively transferred with MDSCs or treated with anti-Gr1 antibody. Results showed that peripheral MDSCs increased significantly with the development of SS-like syndrome in NOD mice and the percentage of MDSCs was higher in SS patients than healthy controls. The SS-like syndrome aggravated after transfer of MDSCs in NOD mice. The deletion of MDSCs in NOD mice alleviated SS-like syndrome. Mechanistically, MDSCs down-regulated the percentages of Th2 cells in NOD mice and SS patients. In summary, our findings suggested that MDSCs exacerbated Sjögren's syndrome by inhibiting Th2 cells.

Accumulating evidence has shown that mammalian target of rapamycin (mTOR) pathway and myeloid-derived suppressor cells (MDSCs) are involved in pathogenesis of inflammatory bowel diseases (IBDs). INK128 is a novel mTOR kinase inhibitor in clinical development. However, the exact roles of MDSCs and INK128 in IBD are unclear. Here, we showed that the INK128 treatment enhanced the resistance of mice to dextran sodium sulfate (DSS)-induced colitis and inhibited the differentiation of MDSCs into macrophages. Moreover, interferon (IFN)-α level was elevated in INK128-treated colitis mice. When stimulated with IFN-α in vitro, MDSCs showed a superior immunosuppression activity. Of note, the regulatory T cells (Tregs) increased but Th1 cells decreased in INK128-treated colitis mice. These results indicate that mTOR inhibitor INK128 attenuates DSS-induced colitis via Treg expansion promoted by MDSCs. Our work provides a new evidence that INK128 is potential to be a therapeutic drug on DSS-induced colitis via regulating MDSCs as well as maintaining Treg expansion.

A new scheme for the estimation of daily global solar radiation over sloped topography in China is developed based on the Iqbal model C and MODIS cloud fraction. The effects of topography are determined using a digital elevation model. The scheme is tested using observations of solar radiation at 98 stations in China, and the results show that the mean absolute bias error is 1.51 MJ m−2 d−1 and the mean relative absolute bias error is 10.57%. Based on calculations using this scheme, the distribution of daily global solar radiation over slopes in China on four days in the middle of each season (15 January, 15 April, 15 July and 15 October 2003) at a spatial resolution of 1 km × 1 km are analyzed. To investigate the effects of topography on global solar radiation, the results determined in four mountains areas (Tianshan, Kunlun Mountains, Qinling, and Nanling) are discussed, and the typical characteristics of solar radiation over sloped surfaces revealed. In general, the new scheme can produce reasonable characteristics of solar radiation distribution at a high spatial resolution in mountain areas, which will be useful in analyses of mountain climate and planning for agricultural production.