Improved cure rate of periprosthetic joint infection through targeted antibiotic therapy based on integrated pathogen diagnosis strategy.

Objectives: This study aimed to determine whether combined of pathogen detection strategies, including specimen acquisition, culture conditions, and molecular diagnostics, can improve treatment outcomes in patients with periprosthetic joint infections (PJI). Methods: This retrospective study included suspected PJI cases from three sequential stages at our institution: Stage A (July 2012 to June 2015), Stage B (July 2015 to June 2018), and Stage C (July 2018 to June 2021). Cases were categorized into PJI and aseptic failure (AF) groups based on European Bone and Joint Infection Society (EBJIS) criteria. Utilization of pathogen diagnostic strategies, pathogen detection rates, targeted antibiotic prescription rates, and treatment outcomes were analyzed and compared across the three stages. Results: A total of 165 PJI cases and 38 AF cases were included in this study. With the progressive implementation of the three optimization approaches across stages A, B and C, pathogen detection rates exhibited a gradual increase (χ2 = 8.282, P=0.016). Similarly, utilization of targeted antibiotic therapy increased stepwise from 57.1% in Stage A, to 82.3% in Stage B, and to 84% in Stage C (χ2 = 9.515, P=0.009). The 2-year infection control rate exceeded 90% in both stages B and C, surpassing stage A (71.4%) (χ2 = 8.317, P=0.011). Combined application of all three optimized protocols yielded the highest sensitivity of 91.21% for pathogen detection, while retaining higher specificity of 92.11%. Conclusion: The utilization of combined pathogen diagnostic strategies in PJI can increase pathogen detection rates, improve targeted antibiotic prescription, reduce the occurrence of antibiotic complications, and achieve better treatment outcomes.

Host specificity of plant-associated bacteria is negatively associated with genome size and host abundance along a latitudinal gradient.

Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient.

Association Between Suboptimal Health Status and Health-Related Productivity Loss in Primary Healthcare Workers in China: a Cross-Sectional Survey.

Objective: This study aimed to clarify the association between suboptimal health status and health-related productivity loss among primary healthcare workers in China. Material and Methods: A field questionnaire survey was conducted with a multistage sampling among primary healthcare workers. The data on sub-health and health-related productivity loss were collected using the Sub-health Measurement Scale Version 1.0 and Work Productivity and Activity Impairment Questionnaire: General Health, respectively. Ordinary least squares regression was used to evaluate the association of the suboptimal health and health-related productivity loss. Subgroup analyses were performed by occupation (physician and nurse). Results: Front-line primary healthcare workers (N = 1709) from 31 provinces in China responded to the survey. Of all participants, 73.43% experienced suboptimal health. The status of being in physical suboptimal health (Coef. = 0.050, p < 0.001, 95% CI = [0.031,0.070]) and mental suboptimal health (Coef. = 0.040, p < 0.001, 95% CI = [0.020,0.059]) status exerted significant effect on the extent of health-related productivity loss among primary healthcare workers in China. Nurses in social adaptation suboptimal health status (Coef. = 0.030, p = 0.027, 95% CI = [0.003,0.057]) had significant effect on health-related productivity loss. Conclusion: The prevalence of suboptimal health is high among the respondents. Providing support for primary healthcare workers from bio-psycho-social aspects is an effective measure to promote their occupational health and improve their productivity.

Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China.

BACKGROUND: To compare the effectiveness, cost, and safety of four regimens recommended by the World Health Organization (WHO) for rifampicin resistance/multidrug-resistance tuberculosis (RR/MDR-TB) Treatment in Eastern China. METHODS: We performed a cohort study among patients with RR/MDR between 2020 and 2022 in Jiangsu Province. The treatment success rate, cost, and drug adverse reaction rate were compared. RESULTS: Between 2020 and 2022, 253 RR/MDR-TB patients were enrolled in the study. 37 (14.62%), 76 (30.04%), 74 (29.25%), and 66 (26.09%) patients had the short-term regimens, the new long-term oral regimens, the new long-term injectable regimens, and the traditional long-term regimens, respectively. The treatment success rate was the highest among patients treated with the short-term regimen (75.68%) and was the lowest among patients treated with the traditional long-term regimens (60.61%). The estimated mean cost per favorable outcome was 142.61 thousand Chinese Yuan (CNY), and the short-term regimens showed the lowest cost in the four regimes (88.51 thousand CNY vs. 174.24 thousand CNY, 144.00 thousand CNY, and 134.98 thousand CNY). Incremental cost-effectiveness ratios of the short-term regimens, the new long-term oral regimen, and the new long-term injectable regimens were -3083.04, 6040.09, and 819.68 CNY compared to the traditional long-term regimens. CONCLUSIONS: For RR/MDR-TB patients in China who meet the criteria for short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO. For RR/MDR-TB patients in China who don't meet the criteria for short-term regimens, the new long-term injectable regimens are more cost-effective than the remaining two regimens.

This is the first study to evaluate the effectiveness, cost, and safety of four regimens recommended by the WHO for RR/MDR-TB treatment in China.For RR/MDR-TB patients in China who meet the criteria for the short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO.

Fatty acid binding protein 4 (FABP4) induces chondrocyte degeneration via activation of the NF-κb signaling pathway.

The pathogenesis of osteoarthritis (OA) is still unclear. Fatty acid binding protein 4 (FABP4), a novel adipokine, has been found to play a role in OA. This study aimed to explore the role of NF-κB in FABP4-induced OA. In the in vivo study, four pairs of 12-week-old male FABP4 knockout (KO) and wild-type (WT) mice were included. The activation of NF-κB was assessed. In parallel, 24 6-week-old male C57/Bl6 mice were fed a high-fat diet (HFD) and randomly allocated to four groups: daily oral gavage with (1) PBS solution; (2) QNZ (NF-κB-specific inhibitor, 1 mg/kg/d); (3) BMS309403 (FABP4-specific inhibitor, 30 mg/kg/d); and (4) BMS309403 (30 mg/kg/d) + QNZ (1 mg/kg/d). The diet and treatment were sustained for 4 months. The knee joints were obtained to assess cartilage degradation, NF-κB activation, and subchondral bone sclerosis. In the in vitro study, a mouse chondrogenic cell line (ATDC5) was cultured. FABP4 was supplemented to stimulate chondrocytes, and the activation of NF-κB was investigated. In parallel, QNZ and NF-κB-specific siRNA were used to inhibit NF-κB. In vivo, the FABP4 WT mice had more significant NF-κB activation than the KO mice. Dual inhibition of FABP4 and NF-κB alleviated knee OA in mice. FABP4 has no significant effect on the activation of the JNK signaling pathway. In vitro, FABP4 directly activated NF-κB in chondrocytes. The use of QNZ and NF-κB-siRNA significantly alleviated the expression of catabolic markers of chondrocytes induced by FABP4. FABP4 induces chondrocyte degeneration by activating the NF-κB pathway.

TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Diversity and biogeography of plant phyllosphere bacteria are governed by latitude-dependent mechanisms.

Predicting and managing the structure and function of plant microbiomes requires quantitative understanding of community assembly and predictive models of spatial distributions at broad geographic scales. Here, we quantified the relative contribution of abiotic and biotic factors to the assembly of phyllosphere bacterial communities, and developed spatial distribution models for keystone bacterial taxa along a latitudinal gradient, by analyzing 16S rRNA gene sequences from 1453 leaf samples taken from 329 plant species in China. We demonstrated a latitudinal gradient in phyllosphere bacterial diversity and community composition, which was mostly explained by climate and host plant factors. We found that host-related factors were increasingly important in explaining bacterial assembly at higher latitudes while nonhost factors including abiotic environments, spatial proximity and plant neighbors were more important at lower latitudes. We further showed that local plant-bacteria associations were interconnected by hub bacteria taxa to form metacommunity-level networks, and the spatial distribution of these hub taxa was controlled by hosts and spatial factors with varying importance across latitudes. For the first time, we documented a latitude-dependent importance in the driving factors of phyllosphere bacteria assembly and distribution, serving as a baseline for predicting future changes in plant phyllosphere microbiomes under global change and human activities.

Cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC: Evidence from China.

Objective: We aimed to evaluate the cost-effectiveness of camrelizumab plus chemotherapy compared with chemotherapy alone as the first-line treatment for patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) without targetable epidermal growth factor receptor or anaplastic lymphoma kinase genetic aberrations in patients in China. Methods: A partitioned survival model was constructed to estimate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC from a Chinese healthcare perspective. Survival analysis was performed to calculate the proportion of patients in each state using data from trial NCT03134872. The cost of drugs was obtained from Menet, and the cost of disease management was obtained from local hospitals. Health state data were obtained from published literature. Both deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were adopted to verify the robustness of the results. Results: Compared with chemotherapy alone, camrelizumab plus chemotherapy provided 0.41 incremental quality-adjusted life years (QALYs) at an incremental cost of $10,482.12. Therefore, the incremental cost-effectiveness ratio of camrelizumab plus chemotherapy was $25,375.96/QALY from the Chinese healthcare perspective, much lower than three times the GDP per capita of China in 2021 ($35,936.09) as the willingness-to-pay threshold. The DSA indicated that the incremental cost-effectiveness ratio was most sensitive to the utility value of progression-free survival, followed by the cost of camrelizumab. The PSA illustrated that camrelizumab had 80% probability of being cost-effective at the threshold of $35,936.09 per QALY gained. Conclusion: The results suggest that camrelizumab plus chemotherapy is a cost-effective choice in the first-line treatment for patients with non-squamous NSCLC in China. Although this study has limitations such as short time of use of camrelizumab, no adjustment of Kaplan-Meier curves and the median overall survival that has not been reached, the difference in results caused by these factors is relatively small.

Trait-mediated leaf retention of atmospheric particulate matter in fourteen tree species in southern China.

Particulate air pollution is a serious threat to human health, especially in urban areas, and trees can act as biological filters and improve air quality. However, studies on greening tree species selection are rare. We measured three particular matter adsorption metrics (PM2.5, PM2.5-10, and PM>10 captured per leaf area) and six functional traits for each of fourteen species and estimated their minimum light requirements based on field surveys. We found that shade-tolerant species captured more coarse particles (PM2.5-10) than light-demanding species. For traits, a strong negative correlation was found between photosynthetic capacity and adsorption capacity for all three PM size fractions, indicating that in comparison to acquisitive species, conservative species captured larger amounts of particles. Moreover, denser wood species and smaller leaves were more efficient in capturing large particles (PM>10), while species with "expensive" leaves (high leaf N or P) were more efficient in capturing fine particles (PM2.5), indicating that capturing large and fine particles was related to mechanical stability traits and leaf surface traits, respectively. Our results demonstrated that the metabolism (e.g., photosynthetic capacity) and chemistry (e.g., leaf N and leaf P) of leaves help explain species capacity to capture PM. We encourage future studies to investigate the ecosystem functions and stress tolerance of tree species with the same framework and trait-based methods.

Motor neurons transplantation alleviates neurofibrogenesis during chronic degeneration by reversibly regulating Schwann cells epithelial-mesenchymal transition.

A novel understanding of peripheral nerve injury is epithelial-mesenchymal transition (EMT), which characterizes the process of dedifferentiation and transformation of Schwann cells after nerve injury. Despite being regarded as an important mechanism for healing nerve injuries, long-term EMT is the primary cause of fibrosis in other tissue organs. The potential mechanism promoting neurofibrosis in the process of chronic degeneration of nerve injury and the effects of motor neurons (MNs) transplantation on neurofibrosis and repair of nerve injury were studied by transcriptome sequencing and bioinformatics analysis, which were confirmed by in vivo and in vitro experiments. Even 3 months after nerve injury, the distal nerve maintained high levels of transforming growth factor ß-1 (TGFß-1) and Snail family transcriptional repressor 2 (Snai2). The microenvironment TGFß-1, Snai2 and endogenous TGFß-1 formed a positive feedback loop in vivo and in vitro, which may contribute to the sustained EMT state and neurofibrogenesis in the distal injured nerve. Inhibiting TGFß-1 and Snai2 expression and reversing EMT can be achieved by transferring MNs to distal nerves, and the removal of transplanted MNs is capable of reactivating EMT and promoting the growth of proximal axons. In conclusion, EMT persisting can be an explanation for distal neurofibrosis and a potential therapeutic target. By reversibly regulating EMT, MNs transplantation can alleviate neurofibrogenesis of distal nerve in chronic degeneration.

Safflor yellow treating angina pectoris: A pharmacoeconomic evaluation and network meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a cardiovascular disease caused by myocardial ischemia. In China, safflor yellow and artemisinin-based combination therapies have been extensively used to treat angina pectoris. METHODS: Efficacies were provided by a network meta-analysis following the PRISMA 2020 checklist. Cost-effectiveness analysis was based on patient perspectives. Two-way and probabilistic sensitivity analyses were conducted to assess the robustness of the study results. RESULTS: Conventional treatment combined with safflower is a better choice against angina pectoris. Sensitivity analysis showed that the model was sensitive to the treatment efficacy rather than the drug cost. CONCLUSION: Conventional treatment combined with safflower injection is suggested to treat angina pectoris. Low molecular weight heparin or compound Danshen-dropping pills can be used to increase the recovery rate of angina pectoris, according to conventional treatment combined with safflower injection.

The Consistency Between the Chinese Essential Medicines List and Treatment Guidelines-Taking Oncology Medicines as an Example.

The concepts of "essential medicine" and "national medicine policy" were first put forward for the first time at the World Health Assembly in 1975 in an effort to alleviate the problem of medicine unavailability in developing and poor countries. The essential medicine system in China has experienced three development stages since 1979, when the concept of essential medicines was first introduced, to actively respond to the call of the World Health Organization. Currently, the essential medicines list published in China is the national essential medicines list (2018 Edition). In this study, we examined the consistency between the essential medicines for treating seven cancers (liver cancer, breast cancer, esophageal cancer, lung cancer, colorectal cancer, gastric cancer, and leukemia) and the recommended medicines by cancer treatment guidelines to determine whether the essential medicines are of high quality for clinical needs. The results indicated that the degree of similarity between oncology medicines on the essential medicines list and oncology medicines recommended by guidelines was low, with the majority falling between 30 and 60%. Therefore, to improve the quality of essential medicines, it is necessary to further improve the matching degree. In addition, to further improve the consistency between the essential medicines list and treatment guidelines, the following suggestions are put forward in this paper: (1). Formulate universal treatment guidelines; (2). When selecting essential medicines, greater consideration should be given to those recommended in the guidelines; (3). The essential medicines list and treatment guidelines should be concurrently updated; (4). The cycle for updating the essential medicines list and treatment guidelines should be shortened.

Clinical Outcomes of Culture-Negative and Culture-Positive Periprosthetic Joint Infection: Similar Success Rate, Different Incidence of Complications.

OBJECTIVE: To compare the clinical outcomes of culture-negative periprosthetic joint infection (CN PJI) with those of culture-positive periprosthetic joint infection (CP PJI). METHODS: This study retrospectively examined data from 77 patients who underwent revision surgery due to periprosthetic joint infection (PJI) after hip and knee arthroplasty at our center from January 2012 to June 2017. There were 37 males and 40 females, with an average age of 63.6 year. All patients were classified by Tsukayama type, according to the bacterial culture results of synovial fluid and pre- and intraoperative tissues, 24 cases were included in the CN PJI group, and 53 cases were included in the CP PJI group. All patients underwent routine blood tests, liver, renal function tests, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) measurements. The remission rates of CN PJI and CP PJI were compared. The effects of the culture results on the curative effect were further compared by survival analysis. RESULTS: The patients were followed regularly with an average of 29.2 months (range, 12-76 months). In total, there were 24 cases of CN PJI, with an incidence of 29.63%. The overall success rate of CN PJI group was 86.4% (19/22), and overall success rate of CP PJI group was 87.5% (42/48). The relative efficacy of various surgical options was: one-stage revision 100% (7/7), two-stage revision 96.3% (26/27), debridement and implant retention 64.3% (9/14), respectively. There was no significant difference in the success rate between the CN PJI group and the CP PJI group. The incidence of antibiotic-related complications for the CN PJI group was significantly higher than that of the CP PJI group, with 58.3% for CN PJI and 11.3% for CP PJI, respectively. CONCLUSION: When CN PJI was treated according to the strict standards for the diagnosis and treatment, the success rate of treatment for the CN PJI group was similar to that for the CP PJI group. The incidence of antibiotic-related complications from the CN PJI group was higher than that from the CP PJI group.

The Effects of Species Abundance, Spatial Distribution, and Phylogeny on a Plant-Ectomycorrhizal Fungal Network.

Plant and root fungal interactions are among the most important belowground ecological interactions, however, the mechanisms underlying pairwise interactions and network patterns of rhizosphere fungi and host plants remain unknown. We tested whether neutral process or spatial constraints individually or jointly best explained quantitative plant-ectomycorrhizal fungal network assembly in a subtropical forest in southern China. Results showed that the observed plant-ectomycorrhizal fungal network had low connectivity, high interaction evenness, and an intermediate level of specialization, with nestedness and modularity both greater than random expectation. Incorporating information on the relative abundance and spatial overlap of plants and fungi well predicted network nestedness and connectance, but not necessarily explained other network metrics such as specificity. Spatial overlap better predicted pairwise species interactions of plants and ectomycorrhizal fungi than species abundance or a combination of species abundance and spatial overlap. There was a significant phylogenetic signal on species degree and interaction strength for ectomycorrhizal fungal but not for plant species. Our study suggests that neutral processes (species abundance matching) and niche/dispersal-related processes (implied by spatial overlap and phylogeny) jointly drive the shaping of a plant-ectomycorrhizal fungal network.

Current development and prospects of deep learning in spine image analysis: a literature review.

Background and Objective: As the spine is pivotal in the support and protection of human bodies, much attention is given to the understanding of spinal diseases. Quick, accurate, and automatic analysis of a spine image greatly enhances the efficiency with which spine conditions can be diagnosed. Deep learning (DL) is a representative artificial intelligence technology that has made encouraging progress in the last 6 years. However, it is still difficult for clinicians and technicians to fully understand this rapidly evolving field due to the diversity of applications, network structures, and evaluation criteria. This study aimed to provide clinicians and technicians with a comprehensive understanding of the development and prospects of DL spine image analysis by reviewing published literature. Methods: A systematic literature search was conducted in the PubMed and Web of Science databases using the keywords "deep learning" and "spine". Date ranges used to conduct the search were from 1 January, 2015 to 20 March, 2021. A total of 79 English articles were reviewed. Key Content and Findings: The DL technology has been applied extensively to the segmentation, detection, diagnosis, and quantitative evaluation of spine images. It uses static or dynamic image information, as well as local or non-local information. The high accuracy of analysis is comparable to that achieved manually by doctors. However, further exploration is needed in terms of data sharing, functional information, and network interpretability. Conclusions: The DL technique is a powerful method for spine image analysis. We believe that, with the joint efforts of researchers and clinicians, intelligent, interpretable, and reliable DL spine analysis methods will be widely applied in clinical practice in the future.

Traditional use and safety evaluation of combination Traditional Chinese Medicine in European registration: with XiaoYao Tablets as an example.

Mental health disorders such as stress, anxiety, depression and insomnia caused by COVID-19 have attracted worldwide attention. Traditional Chinese medicines (TCMs) have been proven to be a safe and effective option for treating mental health disorders. Recently, after assessing its efficacy and safety fully, the Netherlands Medicines Evaluation Board approved XiaoYao Tablets as a traditional herbal medicinal product (THMP), indicated for an alternative self-care for patients in Europe to relieve the symptoms of mental stress and exhaustion. Despite the fact that TCMs have gradually become one of the therapeutic choices worldwide, to-date, only a few TCMs have been successfully registered in the European Union (EU) as THMPs, and XiaoYao Tablets is the first successfully registered combination TCM from China. In this article, traditional use efficacy and clinical safety of XiaoYao Tablets in the treatment of mental health disorders were summarized and analyzed from the perspective of traditional use registration (TUR). Additionally a safety evolution pathway of combination TCMs was established. This article will not only seek to enhance our understanding about traditional use efficacy and clinical safety of XiaoYao Tablets, but also summarize the experience of XiaoYao Tablets as the first successfully registered combination TCM from China, which could serve as role model for the others to overcome registration difficulties in the EU.

A mechanistic model for nitrogen-limited plant growth.

BACKGROUND AND AIMS: Nitrogen is often regarded as a limiting factor to plant growth in various ecosystems. Understanding how nitrogen drives plant growth has numerous theoretical and practical applications in agriculture and ecology. In 2004, Göran I. Ågren proposed a mechanistic model of plant growth from a biochemical perspective. However, neglecting respiration and assuming stable and balanced growth made the model unrealistic for plants growing in natural conditions. The aim of the present paper is to extend Ågren's model to overcome these limitations. METHODS: We improved Ågren's model by incorporating the respiratory process and replacing the stable and balanced growth assumption with a three-parameter power function to describe the relationship between nitrogen concentration (Nc) and biomass. The new model was evaluated based on published data from three studies on corn (Zea mays) growth. KEY RESULTS: Remarkably, the mechanistic growth model derived in this study is mathematically equivalent to the classical Richards model, which is the most widely used empirical growth model. The model agrees well with empirical plant growth data. CONCLUSIONS: Our model provides a mechanistic interpretation of how nitrogen drives plant growth. It is very robust in predicting growth curves and the relationship between Nc and relative growth rate.

The role of circRNA derived from RUNX2 in the serum of osteoarthritis and its clinical value.

BACKGROUND: Circular RNA (circRNA) has been shown to affect the pathological process of osteoarthritis (OA) and is expected to become a potential marker for disease diagnosis. This study aimed to investigate the association between circRNA derived from the gene of runt-related transcription factor 2 (RUNX2) and OA risk. METHODS: The expression profile of RUNX2-derived circRNAs in serum of OA patients was detected. Then, the cytological localization of screened differential circRNAs was studied. Luciferase (LUC) reporter assay was used to identify the microRNA (miRNA) sponge capacity of the circRNAs. Bioinformatics analysis was used to construct the functional pathway of this circRNA-miRNAs network. And then, the diagnostic value of RUNX2-derived circRNAs in OA was evaluated. RESULTS: RUNX2-derived hsa_circ_0005526 (circ_RUNX2) is significantly highly expressed in OA serum and mainly located in the cytoplasm within the cartilage cell by sponging multiple miRNAs (miR-498, miR-924, miR-361-3p, and miR-665). Bioinformatics analysis showed ECM-receptor interaction pathway ranked the most significant pathway of circ_RUNX2-miRNAs regulatory network in KEGG database. The ROC curve showed that there may be good diagnostic value of serum circ_RUNX2 in OA. CONCLUSION: RUNX2-derived circ_RUNX2 may be involved in OA development via ECM-receptor interaction pathways and may be used as potential clinical indicator of OA.

Direct effects of selection on aboveground biomass contrast with indirect structure-mediated effects of complementarity in a subtropical forest.

Understanding the multiple biotic and abiotic controls of aboveground biomass (AGB) is important for projecting the consequences of global change and to effectively manage carbon storage. Although large-scale studies have identified the major environmental and biological controls of AGB, drivers of local-scale variation are less well known. Additionally, involvement of multiple causal paths and scale dependence in effect sizes potentially confounds comparisons among studies differing in methodology and sampling grain. We tested for scale dependence in evidence supporting selection, complementarity and environmental factors as the main determinants of AGB variation over a 50 ha study extent in subtropical China, modelling this at four sampling grains (0.01, 0.04, 0.25 and 1 ha). At each grain, we used piecewise structural equation models to quantify the direct and indirect effects of environmental (topographic and edaphic properties) and forest attributes (structure, diversity and functional traits) on AGB, while controlling for spatial autocorrelation. Direct scale-invariant effects on AGB were evident for structure and community-mean traits, supporting dominance of selection effects. However, diversity had strong indirect effects on AGB via forest structure, particularly at larger sampling grains (≥ 0.25 ha), while direct effects only emerged at the smallest grain size (0.01 ha). The direct and indirect effects of edaphic and topographic factors were also important for explaining both forest attributes and AGB across all scales. Although selection effects appeared to be more influential on ecosystem function, ignoring indirect causal pathways for diversity via structural attributes risks overlooking the importance of complementarity on ecosystem functioning, particularly as sampling grain increases.

miR-3574 ameliorates intermittent hypoxia-induced cardiomyocyte injury through inhibiting Axin1.

OBJECTIVE: miRNAs play critical roles in the regulation of many cardiovascular diseases. However, its role and potential mechanism in cardiac injury caused by obstructive sleep apnea (OSA) remain poorly elucidated. In the present study, we aimed to investigate the effects of miR-3574 on cardiomyocyte injury under intermittent hypoxia (IH). RESULTS: We confirmed that IH inhibited cell viability, induced cell apoptosis and suppressed miR-3574 expression in the H9c2. miR-3574 overexpression could ameliorate the effects of IH on the cell viability and cell apoptosis in the H9c2. Axin1 was a target gene of miR-3574, and miR-3574 overexpression reduced the expression of Axin1. miR-3574 could inhibit the IH-induced cardiomyocyte injury via downregulating Axin1. However, Axin1 could partially reverse these effects of miR-3574. CONCLUSION: Our study first reveals that miR-3574 could alleviate IH-induced cardiomyocyte injury by targeting Axin1, which may function as a novel and promising therapy target for OSA-associated cardiovascular diseases. METHODS: H9c2 were exposed to IH condition. CCK-8 assay was applied to determine cell viability of H9c2. qRT-PCR was conducted to measure the expression level of mRNA and miRNA. Western blot assay was then performed to detect the protein levels. Finally, we used dual-luciferase reporter assay identify the potential target of miR-3574.