SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis.

Endothelial dysfunction (ED) is commonly considered a crucial initiating step in the pathogenesis of numerous cardiovascular diseases. The coupling of endothelial nitric oxide synthase (eNOS) is important in maintaining normal endothelial functions. However, it still remains elusive whether and how eNOS SUMOylation affects the eNOS coupling. In the study, we investigate the roles and possible action mechanisms of protein inhibitor of activated STAT 1 (PIAS1) in ED. Human umbilical vein endothelial cells (HUVECs) treated with palmitate acid (PA) in vitro and ApoE-/- mice fed with high-fat diet (HFD) in vivo were constructed as the ED models. Our in vivo data show that PIAS1 alleviates the dysfunction of vascular endothelium by increasing nitric oxide (NO) level, reducing malondialdehyde (MDA) level, and activating the phosphatidylinositol 3-kinase-protein kinase B-endothelial nitric oxide synthase (PI3K-AKT-eNOS) signaling in ApoE-/- mice. Our in vitro data also show that PIAS1 can SUMOylate eNOS under endogenous conditions; moreover, it antagonizes the eNOS uncoupling induced by PA. The findings demonstrate that PIAS1 alleviates the dysfunction of vascular endothelium by promoting the SUMOylation and inhibiting the uncoupling of eNOS, suggesting that PIAS1 would become an early predictor of atherosclerosis and a new potential target of the hyperlipidemia-related cardiovascular diseases.

COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation.

COL1A1::PDGFB fusion uterine sarcoma is a rare uterine mesenchymal tumor with some clinicopathological features that overlap with those of soft tissue dermatofibrosarcoma protuberans. However, the varied clinicopathologic and genetic characteristics have not been fully revealed, which may be a potential pitfall for diagnosis. Here, we present a case of COL1A1::PDGFB fusion-positive uterine sarcoma in a 49-years-old female. Histologically, the tumor from the initial marginal excision predominantly exhibited high-grade fibrosarcomatous and myxofibrosarcoma-like appearances, while a low-grade focal area displaying storiform growth was identified in the residual tumor after subsequently extended resection. Immunohistochemically, the high-grade components mainly exhibited focal positivity for CD34 and mutated-type p53 immunoreactivity, whereas the low-grade component showed diffuse positivity for CD34 and wild-type p53 staining. The COL1A1::PDGFB fusion was confirmed by fluorescence in situ hybridization and next-generation sequencing. In addition, the TERT-124 C > T mutation was further identified in this lesion's fibrosarcomatous and classic storiform components. To the best of our knowledge, this is the first described case of COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation, which might be a novel genetic finding associated with tumorigenesis of this rare tumor.

Asprosin contributes to pathogenesis of obesity by adipocyte mitophagy induction to inhibit white adipose browning in mice.

BACKGROUND: Asprosin (ASP) is a newly discovered adipokine secreted by white adipose tissue (WAT), which can regulate the homeostasis of glucose and lipid metabolism. However, it is not clear whether it can regulate the browning of WAT and mitophagy during the browning process. Accordingly, this study aims to investigate the effects and possible mechanisms of ASP on the browning of WAT and mitophagy in vivo and in vitro. METHODS: In in vivo experiments, some mouse models were used including adipose tissue ASP-specific deficiency (ASP-/-), high fat diet (HFD)-induced obesity and white adipose browning; in in vitro experiments, some cell models were also established and used, including ASP-deficient 3T3-L1 preadipocyte (ASP-/-) and CL-316243 (CL, 1 µM)-induced browning. Based on these models, the browning of WAT and mitophagy were evaluated by morphology, functionality and molecular markers. RESULTS: Our in vivo data show that adipose tissue-specific deletion of ASP contributes to weight loss in mice; supplementation of ASP inhibits the expressions of browning-related proteins including UCP1, PRDM16 and PGC1ɑ during the cold exposure-induced browning, and promotes the expressions of mitophagy-related proteins including PINK1 and Parkin under the conditions of whether normal diet (ND) or HFD. Similarly, our in vitro data also show that the deletion of ASP in 3T3-L1 cells significantly increases the expressions of the browning-related proteins and decreases the expressions of the mitophagy-related proteins. CONCLUSIONS: These data demonstrate that ASP deletion can facilitate the browning and inhibit mitophagy in WAT. The findings will lay an experimental foundation for the development of new drugs targeting ASP and the clinical treatment of metabolic diseases related to obesity.

Valproic acid regulates the miR-155/Jarid2 axis by affecting miR-155 promoter methylation in glioma.

The most frequent primary brain tumor in adults is glioma, yet no effective curative treatments are currently available. Our previous study demonstrated the enhancing effects of JARID2 on glioma sensitivity to TMZ treatment. In this study, miR-155 is predicted to target JARID2. miR-155 is overexpressed in clinical glioma specimens and cell lines. miR-155 overexpression in glioma cells enhances cell viability and represses cell apoptosis. Through targeting, miR-155 inhibits JARID2 expression. miR-155 inhibition inhibits glioma cell viability and enhances cell apoptosis, whereas JARID2 knockdown enhances cell viability and inhibits cell apoptosis; JARID2 knockdown partially reverses miR-155 inhibition effects on glioma phenotypes. miR-155 inhibition reduces but knockdown of JARID2 promotes the tumor formation ability of glioma cells in vivo. Valproic acid (VPA) upregulates JARID2 expression, inhibits glioma cell viability and enhances cell apoptosis. VPA downregulates the expression level of miR-155 by increasing the methylation level of the miR-155 promoter, suggesting that the miR-155/JARID2 axis is implicated in VPA inhibition of glioma cell viability and enhancement of glioma cell apoptosis. This study demonstrates a new mechanism of VPA treatment of gliomas by affecting the miR-155/JARID2 axis, which could be regarded as a new strategy for the prevention and treatment of glioma.

Asprosin aggravates nonalcoholic fatty liver disease via inflammation and lipid metabolic disturbance mediated by reactive oxygen species.

Asprosin (ASP) is a newly-identified adipokine and plays important roles in energy metabolism homeostasis. However, there is no report on whether and how ASP is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, in the study, we investigated the protective effects of ASP-deficiency on the liver in the NAFLD model mice and the detrimental effects of ASP treatment on the human normal hepatocytes (LO2 cell line). More important, we explored the underlying mechanism from the perspective of lipid metabolism and inflammation. In the in vivo experiments, our data showed that the ASP-deficiency significantly alleviated the high-fat diet-induced inflammation and NAFLD, inhibited the hepatic fat deposition and downregulated the expressions of fat acid synthase (FASN), peroxisome proliferator-activated receptor γ (PPARγ) and forkhead box protein O1 (FOXO1); moreover, the ASP-deficiency attenuated the inflammatory state and inhibited the activation of the IKK/NF-κBp65 inflammation pathway. In the in vitro experiments, our results revealed that ASP treatment caused and even exacerbated the injury of LO2 cells induced by FFA; In contrast, the ASP treatment upregulated the expressions of PPARγ, FOXO1, FASN, ACC and acyl-CoA oxidase 1 (ACOX1) and elevated the reactive oxygen species (ROS) levels. Accordingly, these results demonstrate that ASP causes NAFLD through disrupting lipid metabolism and promoting the inflammation mediated by ROS.

Operando Spectroscopic Analysis of Axial Oxygen-Coordinated Single-Sn-Atom Sites for Electrochemical CO2 Reduction.

Sn-based materials have been demonstrated as promising catalysts for the selective electrochemical CO2 reduction reaction (CO2RR). However, the detailed structures of catalytic intermediates and the key surface species remain to be identified. In this work, a series of single-Sn-atom catalysts with well-defined structures is developed as model systems to explore their electrochemical reactivity toward CO2RR. The selectivity and activity of CO2 reduction to formic acid on Sn-single-atom sites are shown to be correlated with Sn(IV)-N4 moieties axially coordinated with oxygen (O-Sn-N4), reaching an optimal HCOOH Faradaic efficiency of 89.4% with a partial current density (jHCOOH) of 74.8 mA·cm-2 at -1.0 V vs reversible hydrogen electrode (RHE). Employing a combination of operando X-ray absorption spectroscopy, attenuated total reflectance surface-enhanced infrared absorption spectroscopy, Raman spectroscopy, and 119Sn Mössbauer spectroscopy, surface-bound bidentate tin carbonate species are captured during CO2RR. Moreover, the electronic and coordination structures of the single-Sn-atom species under reaction conditions are determined. Density functional theory (DFT) calculations further support the preferred formation of Sn-O-CO2 species over the O-Sn-N4 sites, which effectively modulates the adsorption configuration of the reactive intermediates and lowers the energy barrier for the hydrogenation of *OCHO species, as compared to the preferred formation of *COOH species over the Sn-N4 sites, thereby greatly facilitating CO2-to-HCOOH conversion.

Switching the Oxygen Evolution Mechanism on Atomically Dispersed Ru for Enhanced Acidic Reaction Kinetics.

Designing stable single-atom electrocatalysts with lower energy barriers is urgent for the acidic oxygen evolution reaction. In particular, the atomic catalysts are highly dependent on the kinetically sluggish acid-base mechanism, limiting the reaction paths of intermediates. Herein, we successfully manipulate the steric localization of Ru single atoms at the Co3O4 surface to improve acidic oxygen evolution by precise control of the anchor sites. The delicate structure design can switch the reaction mechanism from the lattice oxygen mechanism (LOM) to the optimized adsorbate evolution mechanism (AEM). In particular, Ru atoms embedded into cation vacancies reveal an optimized mechanism that activates the proton donor-acceptor function (PDAM), demonstrating a new single-atom catalytic pathway to circumvent the classic scaling relationship. Steric interactions with intermediates at the anchored Ru-O-Co interface played a primary role in optimizing the intermediates' conformation and reducing the energy barrier. As a comparison, Ru atoms confined to the surface sites exhibit a lattice oxygen mechanism for the oxygen evolution process. As a result, the delicate atom control of the spatial position presents a 100-fold increase in mass activity from 36.96 A gRu(ads)-1 to 4012.11 A gRu(anc)-1 at 1.50 V. These findings offer new insights into the precise control of single-atom catalytic behavior.

Identification of a single cell-based signature for predicting prognosis risk and immunotherapy response in patients with glioblastoma.

This study constructed a novel gene pair signature based on bulk and single-cell sequencing samples in relative expression order within the samples. The subsequent analysis included glioma samples from Xiangya Hospital. Gene pair signatures possessed a solid ability to predict the prognosis of glioblastoma and pan-cancer. Samples having different malignant biological hallmarks were distinguished by the algorithm, with the high gene pair score group featuring classic copy number variations, oncogenic mutations, and extensive hypomethylation, mediating poor prognosis. The increased gene pair score group with a poorer prognosis demonstrated significant enrichment in tumor and immune-related signaling pathways while presenting immunological diversity. The remarkable infiltration of M2 macrophages in the high gene pair score group was validated by multiplex immunofluorescence, suggesting that combination therapies targeting adaptive and innate immunity may serve as a therapeutic option. Overall, a gene pair signature applicable to predict prognosis hopefully provides a reference to guide clinical practice.

Bioactive compounds in cruciferous sprouts and microgreens and the effects of sulfur nutrition.

Cruciferous sprouts and microgreens are a good source of bioactive compounds for human health as they are rich in glucosinolates, polyphenols, carotenoids, and vitamins. Glucosinolates - sulfur-containing bioactive phytochemicals - have anti-cancer effects. They mainly exist in cruciferous vegetables. Sulfur is one of the essential elements for plants and is an indispensable component of glucosinolates. This paper summarizes the nutritional value of cruciferous spouts and microgreens, along with the effects of sulfur nutrition on bioactive phytochemical compounds of cruciferous sprouts and microgreens, especially glucosinolates, with the aim of providing information about the dietary effects of cruciferous sprouts and microgreens. © 2023 Society of Chemical Industry.

Glioma targeted therapy: insight into future of molecular approaches.

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.

The effect of inulin-type fructans on the intestinal immune function of antibiotic-treated mice.

This study aimed to evaluate the effect of supplementation with inulin-type fructans (ITFs) on the intestinal immune function in the context of dysbiosis resulting from antibiotic cocktail (ABx) treatment. BALB/c mice (8-9 weeks of age) were treated with an ABx for 3 weeks and then allowed to recover spontaneously or with ITF supplementation (5%) for 4 weeks. Our results showed that ABx treatment can induce gut microbiota dysbiosis and intestinal inflammation in mice. After 4 weeks of recovery, ITF supplementation restored the composition of the intestinal microbial community. However, compared with spontaneous recovery, ITF supplementation delayed inflammation recovery in the intestine and upregulated diamine oxidase (DAO) activity and increased lipopolysaccharide (LPS) content in serum. In addition, ITF supplementation delayed the regulatory T (Treg) cell and B cell recovery in the lamina propria (LP). Furthermore, compared with spontaneous recovery, ITF supplementation inhibited the relative expression of certain proinflammatory genes, such as for inducible nitric oxide synthase (iNOS) and tumour necrosis factor α (Tnf-α), in the colon, but it reduced the secretion of the anti-inflammatory mediator transforming growth factor ß1 (TGF-ß1) in serum, reduced the secretion of secretory immunoglobulin A (SIgA) in the colon and promoted the secretion of the proinflammatory cytokine interleukin (IL)-17A. In conclusion, these data supported the hypothesis that the influence of ITFs on the host's intestinal status is not always beneficial in the context of ABx-induced biological disorder. However, the significance of these findings needs to be determined by advanced studies KEY POINTS: • ITFs did not promote the recovery of microbial community composition. • ITFs delayed the recovery of ABx-induced colonic inflammation. • ITFs reduced the secretion of TGF-ß1 and SIgA. • ITFs delayed the recovery of Treg and B cells in the LP.

HaCYC2c regulating the heteromorphous development and functional differentiation of florets by recognizing HaNDUA2 in sunflower.

KEY MESSAGE: The overexpression of HaCYC2c and its regulation on HaNDUA2 through transcriptional recognition are important for regulating the heteromorphous development and functional differentiation of ray and disc florets in sunflower. Flower symmetry is closely related to pollinator recruitment and individual fecundity for higher plants and is the main feature used to identify flower type in angiosperms. In sunflower, HaCYC2c regulates floral organ development and floral symmetry, but the specific detail remains unclear. In this study, sunflower long petal mutant (lpm) with HaCYC2c insertion mutation was used to investigate the regulating role of HaCYC2c in the morphogenesis of florets and the transformation of floral symmetry through phenotype, transcriptome, qRT-PCR, and possible protein-gene interactions analyses. Results showed that HaCYC2c was overexpressed after an insertion into the promoter region. This gene could recognize the cis-acting element GGTCCC in the promoter region of HaNDUA2 that might regulate HaNDUA2 and affect other related genes. As a consequence, the abnormal elongation of disc petals and the degradation of male reproductive system occurred at the early development of floral organ in sunflower. Furthermore, this insertion mutation resulted in floral symmetry transformation, from actinomorphy to zygomorphy, thereby making the tubular disc florets transformed into ray-like disc florets in sunflower lpm. The findings suggested that the overexpression of HaCYC2c and its control of HaNDUA2 through transcriptional recognition might be an important regulating node of the heteromorphous development and functional differentiation for ray and disc florets in sunflower. This node contributes to the understanding of the balance between pollinator recruitment capacity of ray florets and fertility of disc florets for the optimization of reproductive efficiency and enhancement of species competitiveness in sunflower.

Transcriptome expression profiles reveal response mechanisms to drought and drought-stress mitigation mechanisms by exogenous glycine betaine in maize.

Drought stress is one of the major abiotic stresses that limit growth, development and yield of maize crops. To better understand the responses of maize inbred lines with different levels of drought resistance and the molecular mechanism of exogenous glycine betaine (GB) in alleviating drought stress, the responses of two maize inbred lines to drought stress and to the stress-mitigating effects of exogenous GB were investigated. Seedling morphology, physiological and biochemical indexes, root cell morphology and root transcriptome expression profiles were compared between a drought-tolerant inbred line Chang 7-2 and drought-sensitive inbred line TS141. Plants of both lines were subjected to treatments of drought stress alone and drought stress with application of exogenous GB. The results showed that with the increase of drought treatment time, the growth and development of TS141 were inhibited, while those of Chang 7-2 were not significantly different from those of the control (no drought stress and GB). Compared with the corresponding data of the drought-stress group, every index measured from the two inbred lines indicated mitigating effects from exogenous GB, and TS141 produced stronger mitigating responses due to the GB. Transcriptome analysis showed that 562 differentially expressed genes (DEGs) were up-regulated and 824 DEGs were down-regulated in both inbred lines under drought stress. Due to the exogenous GB, 1061 DEGs were up-regulated and 424 DEGs were down-regulated in both lines. In addition, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify 10 DEGs screened from the different treatments. These results showed that the expression of 9 DEGs were basically consistent with their respective transcriptome expression profiles. The results of this study provide models of potential mechanisms of drought tolerance in maize as well as potential mechanisms of how exogenous GB may regulate drought tolerance.

Identified lung adenocarcinoma metabolic phenotypes and their association with tumor immune microenvironment.

BACKGROUND: Lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), causes high mortality around the world. Previous studies have suggested that the metabolic pattern of tumor is associated with tumor response to immunotherapy and patient's survival outcome. Yet, this relationship in LUAD is still unknown. METHODS: Therefore, in this study, we identified the immune landscape in different tumor subtypes classified by metabolism-related genes expression with a large-scale dataset (tumor samples, n = 2181; normal samples, n = 419). We comprehensively correlated metabolism-related phenotypes with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in LUAD patients. RESULTS: And we confirmed tumors with activated lipid metabolism tend to have higher immunocytes infiltration and better response to checkpoint immunotherapy. This work highlights the connection between the metabolic pattern of tumor and tumor immune infiltration in LUAD. A scoring system based on metabolism-related gene expression is not only able to predict prognosis of patient with LUAD but also applied to pan-cancer. LUAD response to checkpoint immunotherapy can also be predicted by this scoring system. CONCLUSIONS: This work revealed the significant connection between metabolic pattern of tumor and tumor immune infiltration, regulating LUAD patients' response to immunotherapy.

Peripherally inserted central venous catheter in upper extremities leads to an increase in D-dimer and deep vein thrombosis in lower extremities.

BACKGROUND: The purpose of this study is to elucidate the association between peripherally inserted central venous catheter (PICC) in upper extremities and lower extremity deep venous thrombosis (LEDVT) by observing the changes in D-dimer. METHODS: This was a retrospective cohort study with 3452 patients (104 inserted with PICCs and 3348 without PICC) enrolled at the neurology department from April 1, 2017 to April 1, 2020. The patients underwent color Doppler ultrasound (CDU) and D-dimer examinations. LEDVT-related factors and D-dimer value were analyzed before and after PICC insertion. The predictive value of D-dimer for LEDVT was also evaluated. RESULTS: Univariate logistic regression analysis showed that PICC insertion increased the risk of LEDVT by 9 times and promoted the increase of D-dimer by 5 times. After risk adjustment, multivariate logistic regression analysis showed that PICC insertion increased the risk of LEDVT by 4 times and tripled the risk of D-dimer increase. The concentration of D-dimer was significantly increased after PICC insertion. D-dimer was unsuitable for excluding venous thrombosis in patients inserted with PICCs. CONCLUSIONS: PICC insertion increases the level of D-dimer and the risk of LEDVT. The risks of venous thrombosis need to be assessed in patients inserted with PICCs to ensure the expected clinical outcomes.

The SlTCP26 promoting lateral branches development in tomato.

KEY MESSAGE: The SlTCP26 negatively regulated auxin signal to relieve the apical dominance and suppressed abscisic acid signal to remove the lateral bud dormancy, promoting lateral branches development. Lateral branches formation from lateral buds is a complex regulatory process in higher plants, and the interaction between transcription factors and hormones is indispensable during this process. TCP transcription factors have been reported to regulate lateral branches development, while the detailed function, especially interacting with auxin and ABA during this process, was still ambiguous in tomato. In this study, a branch regulatory gene, SlTCP26, was identified in tomato, and its role along with its interaction to hormones during branch development, as investigated. The results indicated that overexpression of SlTCP26 would promote lateral branches development, and could suppress the expressing of the genes associated with IAA signaling, presenting similar effects in decapitated plants. Conversely, the exogenous IAA application could inhibit the expression of SlTCP26. Furthermore, the expressing of the ABA signaling-related genes was inhibited in SlTCP26 overexpressed tomato, similar to that in decapitated tomato. Our findings suggested that SlTCP26 may be a crucial adjuster for synergistic action between ABA and IAA signals during the development of lateral branches, and it could promote the lateral buds grow into lateral shoots, via inhibiting IAA signal to relieve the apical dominance and suppressing ABA signal to remove the lateral bud dormancy. Our study provided some insights for the development of tomato lateral branches to understand the apical dominance regulatory network.

Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas.

Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87-MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability and induced G0/G1 phase arrest. In addition, down-regulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual-luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at -236 to -230 bp and -1354 to -1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells.

Response of Soil Respiration and Its Components to Warming and Dominant Species Removal along an Elevation Gradient in Alpine Meadow of the Qinghai-Tibetan Plateau.

The Qinghai-Tibetan Plateau is experiencing unprecedented temperature rises and changes in plant community composition owing to global warming. Few studies focused on the combined effects of warming and changes in species composition on soil respiration (Rs). We conducted a 4-year experiment (2015-2018) to examine the influences of warming and dominant plant species removal on Rs and its autotrophic (Ra) and heterotrophic (Rh) components along an elevation gradient (3200, 3700, and 4000 m) for alpine meadow of the Qinghai-Tibetan Plateau. Results showed that warming positively affected Rs, and the stimulation of Rs gradually diminished at 3200 m but remained stable at 3700 and 4000 m as warming progressed. Warming did not influence Ra at all sites. Dominant species removal produced hysteretic behavior that decreased Ra (29%) at 3700 m but increased Ra (55%) at 4000 m in 2018. No significant effect of dominant species removal on Rh was observed. Significant interactive effects of warming and dominant species removal were detected only on Ra at 3700 and 4000 m. Accordingly, under future warming, soil organic matter decomposition at higher elevation will enhance positive feedback to atmospheric CO2 concentration more than that at lower elevation, thus accelerating soil organic carbon loss.

The effect of antibiotic cocktails on host immune status is dynamic and does not always correspond to changes in gut microbiota.

The disruption of the gut microbiota by treatment with an antibiotic cocktail (ABx) can trigger an imbalance in immune homeostasis. However, whether the changes in the intestinal microbiota always correspond to the changes in the physiology and immune homeostasis of the host remains unclear. Here, we analyzed the effects of ABx on immune homeostasis by analyzing the colonic transcriptome with 16S rRNA analysis of the gut microbiota on the 7th and 21st days of continuous treatment with ABx. Our results showed that the composition profile of the gut microbiota was similar after 7 and 21 days of ABx treatment. However, after 21 days of ABx treatment, the intestinal inflammation did not deteriorate further. Instead, the inflammation of the host was relieved, and half of the differentially expressed genes in the colon were restored compared with the 7 days of ABx treatment. Furthermore, the enrichment and network analysis of these restored genes indicated that expression of regenerating islet-derived protein 3ß (Reg3b) and expression of regenerating islet-derived protein 3γ (Reg3g), especially Reg3b, may participate in the regulation of the inflammatory response and affect the changes in host immune homeostasis during continuous ABx treatment. Finally, Spearman's correlation analysis showed that the expression of Reg3b is correlated with the growth of Escherichia-Shigella. Our data demonstrated that even though the disruption of the gut microbiota profile induced by ABx treatment is similar, the host response and immune status will be different at different times.Key Points• Host immune status can change in different ABx treatment times.• Gut microbiota showed same exhaustion state in different ABx treatment times.• Host tried to revert to a certain extent after long-term ABx treatment.• Reg3b may affect the changes in host immune homeostasis during continuous ABx treatment.• The expression of Reg3b correlated with the growth of Escherichia-Shigella.

Mutations of GNAQ, GNA11, SF3B1, EIF1AX, PLCB4 and CYSLTR in Uveal Melanoma in Chinese Patients.

BACKGROUND: The purpose of this study is to determine the mutation frequencies of key driver genes in uveal melanoma (UM) in Chinese patients and to detect associations between metastasis and the mutation of these genes. METHOD: A total of 85 patients with UM were enrolled in this study, including 18 patients with metastasis and 67 without metastasis. Sanger sequencing covering the mutational hotspot regions of the G protein subunit alpha Q (GNAQ), GNA11, splicing factor 3B subunit 1 (SF3B1), X-linked eukaryotic translation initiation factor 1A (EIF1AX), phospholipase C beta 4 (PLCB4) and cysteinyl leukotriene receptor 2 (CYSLTR2) genes was used to analyse the mutations in Chinese patients. RESULTS: The frequencies of GNAQ and GNA11 mutations in UM were 45% (38/85) and 35% (30/85) respectively. The frequencies of SF3B1 and EIF1AX mutations were 37% (31/85) and 9% (8/85) respectively. Only 2 mutations were detected in exon 4 of GNAQ, and no mutations were detected in exon 4 of GNA11. A novel mutation, c.627G>T (Q209H) in GNA11 was found. The detected mutations affecting SF3B1 were c.1873C>T (R625C), c.1874G>A (R625H) and c.1874G>T (R625L). The association between the mutations in SF3B1 and low risk of metastasis was statistically significant (OR 0.17, 95% CI 0.035-0.819). The mutations affecting EIF1AX were -23G>A (5'-UTR), c.5C>G (P2R), c.23G>A (G8Q), c.25G>C (G9A) and c.38_39GC>CT (R13P). No mutations were found in the PLCB4 and CYSLTR2 genes. Unfortunately, information on BRCA1-associated protein 1 could not be obtained. CONCLUSIONS: These data indicate that mutations in the PLCB4 and CYSLTR2 genes are rare in Chinese UM patients. The mutations in GNAQ, GNA11 and EIF1AX were not associated with metastasis, whereas SF3B1 mutations were correlated with low risk of metastasis and demonstrated a protective effect in UM patients in China.