Yersinia ruckeri Infection and Enteric Redmouth Disease among Endangered Chinese Sturgeons, China, 2022.

During October 2022, enteric redmouth disease (ERM) affected Chinese sturgeons at a farm in Hubei, China, causing mass mortality. Affected fish exhibited characteristic red mouth and intestinal inflammation. Investigation led to isolation of a prominent bacterial strain, zhx1, from the internal organs and intestines of affected fish. Artificial infection experiments confirmed the role of zhx1 as the pathogen responsible for the deaths. The primary pathologic manifestations consisted of degeneration, necrosis, and inflammatory reactions, resulting in multiple organ dysfunction and death. Whole-genome sequencing of the bacteria identified zhx1 as Yersinia ruckeri, which possesses 135 drug-resistance genes and 443 virulence factor-related genes. Drug-susceptibility testing of zhx1 demonstrated high sensitivity to chloramphenicol and florfenicol but varying degrees of resistance to 18 other antimicrobial drugs. Identifying the pathogenic bacteria associated with ERM in Chinese sturgeons establishes a theoretical foundation for the effective prevention and control of this disease.

Neurotropin® ameliorates chronic pain associated with scar formation in a mouse model: A gene expression analysis of the inflammatory response.

Background: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin® (NTP) is a nonprotein extract of inflamed skin of rabbits inoculated with vaccinia virus. It has been widely used for the treatment of chronic pain. However, the in vivo effects of NTP on painful scar formation have not been determined. To investigate the molecular mechanisms underlying the effects of NTP on the inflammatory response, we evaluated gene expression in the scar tissues and dorsal root ganglions (DRGs) of mice administered NTP and control mice. Methods and results: Mice injected with saline or NTP were used as controls; other mice were subjected to surgery on the left hind paw to induce painful scar formation, and then injected with saline or NTP. Hind paw pain was evaluated by measuring the threshold for mechanical stimulation using the von Frey test. The paw withdrawal threshold gradually returned to pre-operative levels over 4 weeks post-operation; NTP-treated mice showed a significantly shortened recovery time of approximately 3 weeks, suggesting that NTP exerted an analgesic effect in this mouse model. Total RNA was extracted from the scarred hind paw tissues and DRGs were collected 1 week post-operation for a microarray analysis. Gene set enrichment analysis revealed that the expression of some gene sets related to inflammatory responses was activated or inhibited following surgery and NTP administration. Quantitative real-time reverse transcription-polymerase chain reaction analysis results for several genes were consistent with the microarray results. Conclusion: The administration of NTP to the hind paws of mice with painful scar formation following surgery diminished nociceptive pain and reduced the inflammatory response. NTP inhibited the expression of some genes involved in the response to surgery-induced inflammation. Therefore, NTP is a potential therapeutic option for painful scar associated with chronic pain.

YTHDF1 Promotes Proliferation and Inhibits Apoptosis of Gastric Cancer Cells via Upregulating TCF7 mRNA Translation.

BACKGROUND: N6-methyladenosine (m6A) modification is one of the most common RNA modifications in mammals. m6A modification, and associated abnormal gene expression, occur during various biological processes, most notably tumorigenesis. YTH domain-containing family protein 1 (YTHDF1), a m6A reader, bind to messenger RNAs (mRNAs) containing a m6A modification and this enhances its interaction with the ribosome and promotes translation. The function of YTHDF1 in gastric cancer (GC) has been the subject of earlier studies; however, the precise mechanism underlying YTHDF1's role in GC has not been fully elucidated. METHODS: The expression of YTHDF1 was evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry and western blotting. CCK-8, 5-Ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays were utilized to explore the effect of YTHDF1 on GC cell viability and proliferation. Transcriptome sequencing and RNA immunoprecipitation assays were utilized to explore the underlying mechanisms mediated by YTHDF1. RESULTS: We observed that YTHDF1 is upregulated in GC cancer tissues. Knockdown of YTHDF1 in GC cells significantly inhibited proliferation and promoted apoptosis, suggesting that YTHDF1 increases proliferation and blocks apoptosis in GC cells. Mechanistically, data gathered suggest that YTHDF1 promotes the translation of the transcription factor TCF7 and this results in activation of the WNT signaling axis. CONCLUSIONS: We found that YTHDF1 was upregulated in GC and that YTHDF1 could promote GC progression through modulating the translational efficiency of TCF7. Taken together, these findings may provide a novel therapeutic target for GC.

Propagation properties of a partially coherent electromagnetic hyperbolic-sine-Gaussian vortex beam through anisotropic atmospheric turbulence.

Using the extended Huygens-Fresnel principle and the Rytov approximation, the analytical formula for the propagation of a partially coherent electromagnetic hyperbolic-sine-Gaussian vortex beam (PCEShVB) in anisotropic atmospheric turbulence has been theoretically derived. Detailed studies have been conducted on the evolution characteristics of the average intensity, the degree of coherence (DOC), and the degree of polarization (DOP) of the beam in turbulence. The results show that during propagation, the intensity distribution of the beam will exhibit a spiral structure, and the overall distribution of the light spots will rotate in a direction related to the sign of the topological charge. The DOC distribution of PCEShVB will display a pattern reminiscent of beam interference fringes with an increase in propagation distance, with the number of "interference fringes" greatly impacted by the hyperbolic sine parameter. Furthermore, PCEShVB with a large initial coherent length and hyperbolic sine parameter will increase the degree of separation of the spots and yield a large DOP. Finally, for the validation of the theoretical findings, the random phase screen method was employed to simulate the propagation of PCEShVB through anisotropic atmospheric turbulence. The studies revealed a consistent alignment between the simulation results and the theoretical predictions.

Changes in Microbial Composition During the Succession of Biological Soil Crusts in Alpine Hulun Buir Sandy Land, China.

Biological soil crusts (biocrusts) are considered "desert ecosystem engineers" because they play a vital role in the restoration and stability maintenance of deserts, including those cold sandy land ecosystems at high latitudes, which are especially understudied. Microorganisms participate in the formation and succession of biocrusts, contributing to soil properties' improvement and the stability of soil aggregates, and thus vegetation development. Accordingly, understanding the composition and successional characteristics of microorganisms is a prerequisite for analyzing the ecological functions of biocrusts and related applications. Here, the Hulun Buir Sandy Land region in northeastern China-lying at the highest latitude of any sandy land in the country-was selected for study. Through a field investigation and next-generation sequencing (Illumina MiSeq PE300 Platform), our goal was to assess the shifts in diversity and community composition of soil bacteria and fungi across different stages during the succession of biocrusts in this region, and to uncover the main factors involved in shaping their soil microbial community. The results revealed that the nutrient enrichment capacity of biocrusts for available nitrogen, total nitrogen, total phosphorus, total content of water-soluble salt, available potassium, soil organic matter, and available phosphorus was progressively enhanced by the succession of cyanobacterial crusts to lichen crusts and then to moss crusts. In tandem, soil bacterial diversity increased as biocrust succession proceeded but fungal diversity decreased. A total of 32 bacterial phyla and 11 fungal phyla were identified, these also known to occur in other desert ecosystems. Among those taxa, the relative abundance of Proteobacteria and Cyanobacteria significantly increased and decreased, respectively, along the cyanobacterial crust-lichen-moss crust successional gradient. However, for Actinobacteria, Chloroflexi, and Acidobacteria their changed relative abundance was significantly hump-shaped, increasing in the shift from cyanobacterial crust to lichen crust, and then decreasing as lichen crust shifted to moss crust. In this process, the improved soil properties effectively enhanced soil bacterial and fungal community composition. Altogether, these findings broaden our understanding about how soil microbial properties can change during the succession of biocrusts in high-latitude, cold sandy land ecosystems.

Growing-season drought and nitrogen addition interactively impair grassland ecosystem stability by reducing species diversity, asynchrony, and stability.

Aboveground net primary productivity controls the amount of energy available to sustain all living organisms, and its sustainable provision relies on the stability of grassland ecosystems. Human activities leading to global changes, such as increased nitrogen (N) deposition and the more frequent occurrence of extreme precipitation events, with N addition increasing the sensitivity of ecosystem production stability to changes in the precipitation regime. However, whether N addition, in combination with seasonal precipitation increases or severe drought, affects ecosystem stability remains unclear. In this study, we conducted a six-year environmental change monitoring experiment in a semiarid grassland in northern China to test the effects of N addition, seasonal drought, and precipitation increases on the temporal stability of ecosystem productivity. Our study revealed that an interaction between drought and N addition reduced species diversity, species asynchrony, species stability, and thus ecosystem stability. These environmental change drivers (except for precipitation increase) induced a positive relationship between species asynchrony and diversity, whereas N addition interactively with drought and precipitation increase led to a negative relationship between diversity and species stability. Only N addition interactively with drought induced a positive species diversity-ecosystem stability relationship because lower species stability was overcome by increased species asynchrony. Our study is great importance to illustrate that production temporal stability tends to be inhibited with drought, though interactively with nutrient N addition. These findings highlight the primary role of asynchronous dynamics among species in modulating the effects of environmental change on diversity-stability relationships.

Comprehensive survival nomograms for locally advanced gastric cancer: a large population-based real-world study.

Background: This study aimed to construct and verify nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for locally advanced gastric cancer (LAGC) based on a therapeutic selection, demographic factors, and pathological features. Methods: The data used for the analysis were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed based on the Cox regression model. Results: The entire cohort comprised 21,757 patients with histologically confirmed LAGC, and was randomly distributed into training and verification groups at a ratio of 2:1 for building the prognostic predictive model. According to the multivariate analysis, 13 variables [i.e., age, marital status, race, tumor location, pathological grade, histological type, T and N stage, surgery, radiotherapy, chemotherapy, tumor size, and regional nodes examined (RNE)] were confirmed as independent predictors for both OS and CSS. All of the significant variables were used to create the nomograms for OS and CSS. Time-dependent receiver operating characteristic (ROC) curves, a decision curve analysis (DCA), the C-index, and calibration curves were applied to identify the discriminating superiority of the nomograms. Conclusions: The nomograms for OS and CSS in LAGC were built and validated based on the therapeutic selection and pathological and demographic variables using a national database. This study aims at helping clinicians make better clinical decisions and encouraging patients receive treatment actively.

KDM5 family of demethylases promotes CD44-mediated chemoresistance in pancreatic adenocarcinomas.

A growing body of evidence suggests that the histone demethylase-lysine demethylase 5 (KDM5) family is associated with drug resistance in cancer cells. However, it is still not clear whether KDM5 family members promote chemotherapy resistance in pancreatic ductal adenocarcinomas (PDAC). Comprehensive bioinformatics analysis was performed to investigate the prognostic value, and functional mechanisms of KDM5 family members in PDAC. The effects of KDM5 family members on drug resistance in PDAC cells and the relationship with CD44, as a stem cell marker, were explored by gene knockout and overexpression strategies. Finally, our findings were validated by functional experiments such as cell viability, colony formation and invasion assays. We found that the expression of KDM5A/C was significantly higher in gemcitabine-resistant cells than in sensitive cells, consistent with the analysis of the GSCALite database. The knockdown of KDM5A/C in PDAC cells resulted in diminished drug resistance, less cell colonies and reduced invasiveness, while KDM5A/C overexpression showed the opposite effect. Of note, the expression of KDM5A/C changed accordingly with the knockdown of CD44. In addition, members of the KDM5 family function in a variety of oncogenic pathways, including PI3K/AKT and Epithelial-Mesenchymal Transition. In conclusion, KDM5 family members play an important role in drug resistance and may serve as new biomarkers or potential therapeutic targets in PDAC patients.

Knockdown of circEXOC6 inhibits cell progression and glycolysis by sponging miR-433-3p and mediating FZD6 in glioma.

Background: The effect of circular RNA in many human cancers is widely studied. Nevertheless, their specific biological functions and mechanisms in glioma remain unclear. Methods: CircEXOC6, miR-433-3p, and frizzled class receptor 6 (FZD6) mRNA expression levels were measured by quantitative reverse transcription polymerase chain reaction assay. Cell proliferation, migration, invasion, apoptosis, and angiogenesis were tested by colony formation, cell-light 5-ethynyl-2'-deoxyuridine, transwell, and tube formation assays, respectively. Moreover, glucose consumption and lactate production were calculated to evaluate the glycolytic metabolism using the respective kits. Western blot assay was carried out to measure the protein levels of apoptotic markers (Bcl-2 and Bax), glycolytic markers (HK2 and GLUT1), and FZD6. The targeted relationship of miR-433-3p and circEXOC6 or FZD6 was verified by dual-luciferase reporter or RNA immunoprecipitation assays. In vivo, xenograft and immunohistochemistry assay was conducted to discriminate the effect of circEXOC6. Results: CircEXOC6 and FZD6 were highly expressed, while miR-433-3p was significantly lowly expressed in glioma tissues or cells. Deficiency of circEXOC6 inhibited cell proliferation, migration, invasion, angiogenesis, and glycolysis, and triggered cell apoptosis ratio in glioma; simultaneously, it could block the growth of tumor in vivo. In addition, miR-433-3p was a target of circEXOC6, and downregulated miR-433-3p could partly weaken the inhibitory effect of circEXOC6 deficiency. Besides, miR-433-3p enrichment inhibited cell progression and glycolysis in glioma, and the effect was reversed by overexpression of FZD6. Conclusion: Deletion of circEXOC6 restrained cell progression and glycolysis by sponging miR-433-3p and interacting with FZD6, which might provide an underlying target for glioma treatment.

Building Porous Ni(Salen)-Based Catalysts from Waste Styrofoam via Autocatalytic Coupling Chemistry for Heterogeneous Oxidation with Molecular Oxygen.

The development of robust and industrially viable catalysts from plastic waste is of great significance, and the facile construction of high performance heterogeneous catalyst systems for phenol-quinone conversions remains a grand challenge. Herein, a feasible strategy is demonstrated to reclaim Styrofoam into hierarchically porous nickel-salen-loaded hypercrosslinked polystyrene (PS@Ni-salen) catalysts with high activities through an unusual autocatalytic coupling route. The salen is immobilized onto PS chain by Friedel-Crafts alkylation of benzyl chloride derivatives, and the generated hydrogen chloride coordinately promotes the simultaneous crosslinking and bridge formation between aromatic rings via a Scholl coupling route, leading to hierarchically porous networks. After the metallization with Ni, the resultant networks exhibit high catalytic activity for the oxidation of 2,3,6-trimethylphenol to 2,3,5-trimethyl-1,4-benzoquinone under mild conditions (303 K, 1 bar of O2 ). This catalyst also demonstrates attractive recycling performance without an obvious loss of catalytic efficiency over five consecutive cycles. This methodology might provide a potential sustainable alternative to construct environmentally benign and cost-effective catalysts for specific organic transformation.

Asymmetric pre-growing season warming may jeopardize seed reproduction of the sand-stabilizing shrub Caragana microphylla.

Our current understanding of the processes and mechanisms by which seasonal asymmetric warming affects seed reproduction in semiarid regions, which are essential in preserving the stability of both vegetation ecosystem structure and function, remains poorly understood. Here, we conducted a field warming experiment, including pre-growing season warming (W1), in-growing season warming (W2), and combined pre- and in-growing season warming (W3) treatments, to investigate the seed reproductive strategy of Caragana microphylla, an important sand-stabilizing shrub, from the perspective of reproductive phenology, reproductive effort, and reproductive success. Results show that the warming treatments advanced the initial stages of reproductive phenology, prolonged its duration, and decreased its synchrony (magnitude = W3 > W2 > W1). Additionally, flowering phenology was more sensitive to warming than podding phenology. The W1 treatment inclined seed reproduction towards the conservative strategy with low reproductive effort and success. The W3 treatment tended to increase seed reproductive effort and success. While the W2 treatment did not affect reproductive success, it did increase reproductive effort. Changes in reproductive phenology explained 20 % of the variation in reproductive effort and 38 % of the variation in reproductive success. However, these changes also directly hindered reproductive success (direct effect = -0.57) while indirectly promoting reproductive success (indirect effect = 0.27) by increasing reproductive efforts. Our results reveal that the seasonal asymmetry of warming altered the seed reproduction strategy of sand-stabilizing shrubs, with warmer winters and springs before the growing season decreasing seed fecundity.

Base-Modulated 1,3-Regio- and Stereoselective Carboboration of Cyclohexenes.

While chain-walking stimulates wide interest in both polymerization and organic synthesis, site- and stereoselective control of chain-walking on rings is still a challenging task in the realm of organometallic catalysis. Inspired by a controllable chain-walking on cyclohexane rings in olefin polymerization, we have developed a set of chain-walking carboborations of cyclohexenes based on nickel catalysis. Different from the 1,4-trans-selectivity disclosed in polymer science, a high level of 1,3-regio- and cis-stereoselectivity is obtained in our reactions. Mechanistically, we discovery that the base affects the reduction ability of B2 pin2 and different bases lead to different catalytic cycles and different regioselective products (1,2- Vs 1,3-addition). This study provides a concise and modular method for the synthesis of 1,3-disubstituted cyclohexylboron compounds. The incorporation of a readily modifiable boronate group greatly enhances the value of this method, the synthetic potential of which was highlighted by the synthesis of a series of high-valued commercial chemicals and pharmaceutically interesting molecules.

Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand.

Chiral boronic esters are a class of versatile building blocks. We describe herein an asymmetric nickel-catalyzed borylative coupling of terminal alkenes with nonactivated alkyl halides. The success of this asymmetric reaction is ascribed to the application of a chiral anionic bisoxazoline ligand. This study provides a three-component strategy to access α- and ß-stereogenic boronic esters from easily accessible starting materials. This protocol is characterized by mild reaction conditions, wide substrate scope and high regio- and enantioselectivity. We also showcase the value of this method in simplifying the synthesis of several drug molecules. Mechanistic studies suggest that the generation of enantioenriched boronic esters bearing an α-stereogenic center results from a stereoconvergent process, while the enantioselectivity-controlling step in the generation of boronic esters with a ß-stereocenter is switched to the olefin migratory insertion step due to coordination of an ester group.

Distribution of cardiorespiratory fitness in children and adolescents at different latitudes.

OBJECTIVE: To explore the differences and characteristics of cardiorespiratory fitness (CRF) among children and adolescents in regions with different latitudes in China. METHODS: A total of 9892 children and adolescents aged 7-22 years were selected from seven administrative regions in China by the stratified cluster random sampling method. CRF was measured by performance on the 20 m shuttle run test (20mSRT) and estimated maximal oxygen consumption (VO2max ). One-way ANOVA, one-way ANCOVA, and the Lambda Mu and Sigma methods were used to analyze the data. RESULTS: Overall, the VO2max of children and adolescents at high latitudes was significantly lower than that of children at low and middle latitudes. The P10 , P50 , and P90 20mSRT values for children and adolescents of most age groups in high latitudes were less than those in low and middle latitudes. The 20mSRT-Z and VO2max -Z scores among children and adolescents aged 7-22 in high latitudes were lower than those in middle and low latitudes after adjusting for age, per capita gross domestic product (GDP), and per capita disposable income. CONCLUSION: In general, the CRF of children and adolescents at high latitudes was less than that at low and middle latitudes. Effective measures should be taken to improve CRF in children and adolescents at high latitudes.

Soil extracellular enzyme stoichiometry reflects microbial metabolic limitations in different desert types of northwestern China.

Soil extracellular enzyme activity (EEA) stoichiometry reflects the dynamic balance between microorganism metabolic demands for resources and nutrient availability. However, variations in metabolic limitations and their driving factors in arid desert areas with oligotrophic environments remain poorly understood. In this study, we investigated sites in different desert types in western China and measured the activities of two C-acquiring enzymes (ß-1,4-glucosidase and ß-D-cellobiohydrolase), two N-acquiring enzymes (ß-1,4-N-acetylglucosaminidase and L-leucine aminopeptidase), and one organic-P-acquiring enzyme (alkaline phosphatase) to quantify and compare the metabolic limitations of soil microorganisms based on their EEA stoichiometry. The ratios of log-transformed C-, N-, and P-acquiring enzyme activities for all deserts combined were 1:1.1:0.9, which is close to the hypothetical global mean EEA stoichiometry (1:1:1). We quantified the microbial nutrient limitation by means of vector analysis using the proportional EEAs, and found that microbial metabolism was co-limited by soil C and N. For different desert types, the microbial N limitation increased in the following order: gravel desert < sand desert < mud desert < salt desert. Overall, the study area's climate explained the largest proportion of the variation in the microbial limitation (17.9 %), followed by soil abiotic factors (6.6 %) and biological factors (5.1 %). Our results confirmed that the EEA stoichiometry method can be used in microbial resource ecology research in a range of desert types, and that the soil microorganisms maintained community-level nutrient element homeostasis by adjusting enzyme production to increase uptake of scarce nutrients even in extremely oligotrophic environments such as deserts.

Electrical transport properties of TiO2/MAPbI3 and SnO2/MAPbI3 heterojunction interfaces under high pressure.

The electrical transport properties of SnO2(TiO2)/MAPbI3 (MA = CH3NH3 +) heterojunction interfaces are investigated from ambient pressure to 20 GPa, and the transport properties are calculated by physical parameters such as trap energy density, binding energy, and charge transfer driving force and defect. Based on the partial density of states (PDOS) of the SnO2/MAPbI3 heterojunction interface MAI-termination and PbI2-termination, greater charge transfer driving force and higher binding energy are observed, obviously showing the SnO2-based heterojunction is more stable. The SnO2/MAPbI3 heterojunction interface possesses stronger electrical transport ability and is less prone to capture electrons compared with the TiO2/MAPbI3 heterojunction interface. The differential charge density spectrum shows that the density is lower in the trap energy level of SnO2/MAPbI3, whilst the effect of the charge transfer defect is weaker owing to the trap energy level only existing in SnO2. The SnO2/MAPbI3 heterostructure interface is less prone to capture electrons. The greater electron concentration difference is attributed to oxygen vacancy (Vo0) in the SnO-like environment, resulting in superior electron transport ability compared with the TiO-like environment.

Mapping Chinese annual gross primary productivity with eddy covariance measurements and machine learning.

Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr-1 falling into the range of previous works. Considering the consistency between the generated AGPP and previous products, our optimal mapping way was suitable for mapping AGPP from site measurements. Our results provided a methodological support for mapping regional AGPP and other fluxes.

CIRCKLHL2 KNOCKDOWN ALLEVIATES SEPSIS-INDUCED ACUTE LUNG INJURY BY REGULATING MIR-29B-3P MEDIATED ROCK1 EXPRESSION DOWN-REGULATION.

ABSTRACT: Background: Acute lung injury (ALI) induced by sepsis is distinguished by an inflammatory progression. Herein, we investigated the action of circular RNA kelch like family member 2 (circKlhl2) in sepsis-induced ALI. Methods: The animal or cell model of sepsis ALI was established by LPS stimulation. The contents of circKlhl2, microRNA-29b-3p (miR-29b-3p), rho-associated coiled-coil containing protein kinase 1 (ROCK1), CyclinD1, B-cell lymphoma-2 (Bcl-2), and cleaved-caspase 3 (C-caspase-3) were detected by quantitative real-time polymerase chain reaction and western blot, respectively. Cell viability was assessed by cell counting kit 8 assay. Cell cycle and apoptosis were evaluated by flow cytometry. The abundances of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay. Besides, the targeted relationship between miR-29b-3p and circKlhl2 or ROCK1 was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Results: Loss of circKlhl2 mitigated lung injury and proinflammatory cytokine expression in sepsis-ALI mice model and alleviated LPS-induced apoptosis and inflammatory response in microvascular endothelial cell (MPVECs) in vitro . The abundances of circKlhl2 and ROCK1 were boosted, while the miR-29b-3p level was diminished in the animal or cell model of sepsis-ALI. MiR-29b-3p inhibition abrogated circKlhl2 knockdown-mediated effects on MPVECs injury. Moreover, miR-29b-3p overexpression promoted cell proliferation and inhibited apoptosis and inflammation in LPS-treated MPVECs, while ROCK1 enhancement reversed these effects. Conclusion: CircKlhl2 expedited the sepsis-induced ALI by adjusting miR-29b-3p/ROCK1 axis.

The new 'coN' staging system combining lymph node metastasis and tumour deposit provides a more accurate prognosis for TNM stage III colon cancer.

OBJECTIVE: Despite controversy over its origin and definition, the significance of tumour deposit (TD) has been underestimated in the tumour node metastasis (TNM) staging system for colon cancer, especially in stage III patients. We aimed to further confirm the prognostic value of TD in stage III colon cancer and to establish a more accurate 'coN' staging system combining TD and lymph node metastasis (LNM). METHODS: Information on stage III colon cancer patients with a definite TD status was retrospectively collected from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2017. The effect of TD on prognosis was estimated using Cox regression analysis. Maximally selected rank statistics were used to select the optimal cut-off value of TD counts. The predictive power of conventional N staging and the new coN staging was evaluated and compared by Akaike's information criterion (AIC), Harrell's concordance index (C-index) and time-dependent receiver operating characteristic (ROC) curves. Clinicopathological data of stage III colon cancer patients in the Xiangya database from 2014 to 2018 were collected to validate the coN staging system. RESULTS: A total of 39,185 patients with stage III colon cancer were included in our study: 38,446 in the SEER cohort and 739 in the Xiangya cohort. The incidence of TD in stage III colon cancer was approximately 30% (26% in SEER and 30% in the Xiangya database). TD was significantly associated with poorer overall survival (OS) (HR = 1.37, 95% CI 1.31-1.44, p < 0.001 in SEER). The optimal cut-off value of TD counts was 4, and the patients were classified into the TD0 (count = 0), TD1 (count = 1-3) and TD2 (count ≥ 4) groups accordingly. The estimated 5-year OS was significantly different among the three groups (69.4%, 95% CI 68.8%-70.0% in TD0; 60.5%, 95% CI 58.9%-62.2% in TD1 and 42.6%, 95% CI 39.2%-46.4% in TD2, respectively, p < 0.001). The coN system integrating LNM and TD was established, and patients with stage III colon cancer were reclassified into five subgroups (coN1a, coN1b, coN2a, coN2b and coN2c). Compared with conventional N staging, the coN staging Cox model had a smaller AIC (197097.581 vs. 197358.006) and a larger C-index (0.611 vs. 0.601). The AUCs of coN staging at 3, 5 and 7 years were also greater than those of conventional N staging (0.6305, 0.6326, 0.6314 vs. 0.6186, 0.6197, 0.6160). Concomitant with the SEER cohort results, the coN staging Cox model of the Xiangya cohort also had a smaller AIC (2883.856 vs. 2906.741) and a larger C-index (0.669 vs. 0.633). Greater AUCs at 3, 5 and 7 years for coN staging were also observed in the Xiangya cohort (0.6983, 0.6774, 0.6502 vs. 0.6512, 0.6368, 0.6199). CONCLUSIONS: Not only the presence but also the number of TDs is associated with poor prognosis in stage III colon cancer. A combined N staging system integrating LNM and TD provides more accurate prognostic prediction than the latest AJCC N staging in stage III colon cancer.

Grazing exclusion is more beneficial for restoring soil organic carbon and nutrient balance than afforestation on degraded sandy land.

Introduction: Vegetation restoration is an effective measure to improve the ecosystem service of degraded sandy land ecosystem. However, it is unclear how vegetation restoration on severely desertified land affect soil organic carbon (SOC) sequestration and nutrients balance. Therefore, this study was designed to clarify the response of SOC, total nitrogen (TN), total phosphorus (TP), and the resulting stoichiometric ratios (C:N:P) to afforestation and grazing exclusion, and to quantify their dynamics over time. Methods: We conducted vegetation community investigation and soil sampling in natural sparse-forest grassland (the climax community stage), afforestation (Pinus sylvestris var. mongolica (40-year, 48-year), Caragana microphylla (20-year, 40-year)), and grazing exclusion (20-year, 40-year) in China's Horqin Sandy Land. Soil C:N:P stoichiometry and its driving factors under different restoration measures were then studied. Results: Afforestation and grazing exclusion significantly (p < 0.05) increased SOC, TN, and TP concentrations. Vegetation restoration significantly increased C:N, C:P, and N:P ratios, indicating that nutrient limitations may occur in the later stages of restoration. The C:N, C:P, and N:P ratios after a 40-year grazing exclusion were closest to those of natural sparse-forest grassland. The N:P under grazing exclusion increased from 3.1 to 4.1 with increasing restoration age (from 20 to 40 years), which was close to the national mean values (4.2). Moreover, afforestation may lead to water deficit in the surface soil. Vegetation restoration is the main factor leading to changes in soil C:N:P stoichiometry, and indirectly affects soil C:N:P stoichiometry by altering soil structure and chemical properties. Conclusion: In terms of ecological stoichiometry, grazing exclusion was more conducive to restore SOC and nutrient balance than afforestation on severely desertified land. Due to the poor soil nutrients, attentions should be paid to the soil nutrients and water conditions in the later stages of vegetation restoration. Those findings can provide valuable information for the restoration of degraded sandy land in semi-arid areas.