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[Display omitted] • Environmentally relevant levels of PTC and dPTC reduced the fecundity of F0 parental zebrafish, especially in female zebrafish. • Transgenerational abnormal development occurred in unexposed offspring. • The possible mechanism was related to epigenetic modification involving DNA methylation. Prothioconazole (PTC) is a widely used agricultural fungicide, and its parent and metabolite prothioconazole-desthio (dPTC) have been detected in diverse environmental media. This study was aimed at investigating the gender-dependent effects on adult zebrafish reproduction and intergenerational effects on offspring development following parental exposure to PTC and dPTC. The results showed that after the adult zebrafish (F0) was exposed to 0.5 and 10 μg/L PTC and dPTC for 21 days, the fertility and gametogenesis of female zebrafish were decreased more significantly than that of male zebrafish. After that, three fecundity tests were conducted in the exposure period to explore the development endpoints of F1 embryos/larvae without further treatment with PTC and dPTC exposure. However, PTC and dPTC exposure did lead to abnormal development of F1 embryos, including delayed hatching, shortened body length, abnormal development and significant changes in locomotor behavior. These changes were related to the abnormal expression of sex hormones and the regulation of DNA methylation in F0 fish. In a word, the results of this study showed that parental PTC and dPTC interference have sex-dependent reproductive toxicity on F0 zebrafish, which may be passed on to the next generation through epigenetic modification involving DNA methylation, resulting in alternations in growth phenotype of offspring. [ABSTRACT FROM AUTHOR]

Biosynthesis of D‐allulose has been achieved using ketose 3‐epimerases (KEases), but its application is limited by poor catalytic performance. In this study, we redesigned a genetically encoded biosensor based on a D‐allulose‐responsive transcriptional regulator for real‐time monitoring of D‐allulose. An ultrahigh‐throughput droplet‐based microfluidic screening platform was further constructed by coupling with this D‐allulose‐detecting biosensor for the directed evolution of the KEases. Structural analysis of Sinorhizobium fredii D‐allulose 3‐epimerase (SfDAE) revealed that a highly flexible helix/loop region exposes or occludes the catalytic center as an essential lid conformation regulating substrate recognition. We reprogrammed SfDAE using structure‐guided rational design and directed evolution, in which a mutant M3‐2 was identified with 17‐fold enhanced catalytic efficiency. Our research offers a paradigm for the design and optimization of a biosensor‐based microdroplet screening platform. [ABSTRACT FROM AUTHOR]

Purpose. The study aims to determine the correlation between management care perception and the professional quality of life of intensive care unit (ICU) nurses in China and examine the influencing factors. Design and Methods. A cross-sectional descriptive study was conducted with 486 ICU nurses (response rate: 97.2%) from five tertiary hospitals in China from 1 January to 31 July, 2022, by convenience sampling. Data were collected through the general information questionnaire, the management care assessment scale, and the professional quality of life scale. Findings. The score of management care perception of ICU nurses was (132.24 ± 28.04), and the scores of compassion satisfactory, compassion fatigue, and burnout of professional quality of life were (37.54 ± 7.73), (20.80 ± 6.49), and (17.79 ± 5.14), respectively. Multiple linear regression analysis showed that age and the total score of managed care were positively correlated with the score of compassion satisfaction dimension (β = 1.62, 0.19) and that the total score of perceived management care was negatively correlated with the score of compassion fatigue and job burnout (β = −0.04, −0.07). ICU nurses' perceived level of managerial care was at a moderate level. The younger the nurse and the less managerial care they perceived, the lower their job satisfaction and the greater the burnout. Practice Implications. ICU nurses' perceptions of management care and professional quality of life are at a medium level, and a significant correlation exists between them. Therefore, measures to improve the professional quality of life should be taken. Nursing administrators are obliged to actively create a good atmosphere of management care, reduce the job burnout of ICU nurses, improve their professional quality of life, optimise the quality of nursing service, and stabilise the nursing team. [ABSTRACT FROM AUTHOR]

• IIM patients with myocardial injury had significantly higher YKL-40 concentration than non– myocardial injury. • serum YKL-40 was an independent risk factor for myocardial involvement in IIM. • In this retrospective study, we illustrate the potential of YKL-40 as reliable diagnostic biomarkers for predicting myocardial injury in IIM. To investigate the diagnostic value of serum chitinase-3-like-1 protein (YKL-40) levels for myocardial involvement in idiopathic inflammatory myopathies (IIM). A total of 74 patients with definite IIM who visited Jiangsu Province People's Hospital between May 2018 and January 2022 were enrolled in this retrospective study. Baseline clinical evaluation, laboratory index, electrocardiogram (ECG), echocardiography (ECHO) and cardiac magnetic resonance (CMR) parameters were collected. Serum YKL-40 of all participants was determined by ELISA. Receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of YKL-40 in assessing myocardial involvement in IIM patients. 1. YKL-40 concentration was significantly higher in IIM patients with myocardial injury than without myocardial injury.2. Multivariate logistic regression analysis demonstrated that serum YKL-40 was an independent risk factor for myocardial involvement in IIM.3. YKL-40 > 66.4 ng/ml (AUC = 0.85, 95 % CI 0.75–0.95) predicted myocardial injury in IIM with a sensitivity of 0.75 and specificity of 0.95. Serum YKL-40 could serve as a potential biomarker to predict myocardial injury in IIM patients. [ABSTRACT FROM AUTHOR]

In this work, combining poly (methylene green)/glucose dehydrogenase (PMG/GDH) bioanode with Prussian blue/glucose oxidase (PB/GOD) biocathode, we developed a hybrid bioelectrochemical device based on glucose/O 2 enzymatic biofuel cell (EBFC) to achieve energy conversion and storage. Depending on the reversible redox behaviors, PMG and PB play roles of dual-functional nanomaterials, not only as mediators to accelerate electrons transport between enzymes and electrodes surface, but also as pseudocapacitive materials to achieve energy storage. As a result, this hybrid device exhibited superior performance towards energy storage with a specific capacitance of 158.5 mF cm−2 at the current density of 1 mA cm−2. Meanwhile, a maximum output power density of 783.5 μW cm−2 in the pulse mode could be obtained, which had a prominent increment than that of the prototypical EBFC (87.5 μW cm−2) in the steady state. Furthermore, this hybrid device also exhibited better operational stability in long-term charge/discharge cycles test, at the current pulse of 1 mA cm−2. Through the combination of bioelectrocatalysis and capacitive energy storage, this developed hybrid device achieves effective energy conversion and storage, and provides a high output power to address the insufficient power supply of traditional EBFCs, which may enlarge the practical application of EBFCs in self-powered implantable and wearable devices. [ABSTRACT FROM AUTHOR]

We report here for the first time a self-powered biosensing platform based on graphene/graphdiyne/graphene (GDY-Gr) heterostructure substrate material for ultrasensitive hepatocarcinoma marker (microRNA-21) detection in both electrochemical and colorimetric test modes. The dual-mode signal intuitively displayed on a smartphone fundamentally improves the detection accuracy. In electrochemical mode, the calibration curve is established in the linear range of 0.1–10000 fM, and the detection limit is as low as 0.333 fM (S/N = 3). Simultaneously, colorimetric analysis of the miRNA-21 is realized by using ABTS as an indicator. The detection limit is confirmed as 32 fM (S/N = 3), and miRNA-21 of concentration from 0.1 pM to 1 nM exhibit a linear relationship with R2 = 0.9968. Overall, the combination of GDY-Gr and multiple signal amplification strategy significantly improved the sensitivity by 310 times compared with traditional enzymatic biofuel cells (EBFCs) based detection platform, showing broad application prospects for on-site analysis and future mobile medical services. [Display omitted] • Ultra-sensitive self-powered biosensor platform based on graphdiyne/graphene heterogeneous is designed for liver cancer markers detection. • Dual-mode signal intuitive displayed on a smartphone and fundamentally improve the detection accuracy. • Detection limit are as low as 0.33 fM and 32 fM (S/N = 3) in electrochemical and colorimetric analysis mode, respectively. [ABSTRACT FROM AUTHOR]

Conversing proteinaceous enzyme behavior into nanomaterials is intriguing academically, but the threshold from mimicry to accessing sophisticated biological entities has not yet been crossed. Herein, we disclosed the pan-glycoside hydrolases-like (p-GHs-like) activities of Cu 3 P and Cu 2 O nanoparticles and decently confirmed their consistent catalytic mechanism as natural glycoside hydrolase, that is, the precise bond breaking, anomeric carbon configuration and catalytic attack mode. We then introduced p-GHs-like NPs into Escherichia coli to establish a feedback regulatory model for the β- D -glucuronidase (expressed by uidA) that was initially expressed in trace amounts. An upregulation of uidA from 72 to 1000 counts was induced by the p-GHs-like activities via pre-released β-glucuronides derivatives, further contributing to 1–2 orders enhancement of the enzyme production. We unearthed the specific catalytic mechanism to unlock a black box of enzyme-like inorganic feedback on the natural enzyme synthesis process, pushing mimicry leaped to physiological behavior. [Display omitted] • Reaction types. Cu 3 P and Cu 2 O NPs possess pan-glycoside hydrolases-like activities (p-GHs-like). • Their catalytic attack mode, precise bond breaking and configuration changes are consistent with natural GHs. • Physiological behavior. The feedback regulation of p-GHs-like NPs on GUS expression in E. coli is given. • β- D -glucuronidase. GUS is critical enzyme for detection of gut bacterial contamination in water. [ABSTRACT FROM AUTHOR]

Obesity caused by endocrine disruptors (EDCs) has become a hot topic threatening human health. Recently, Nanoselenium Siraitia grosvenorii (NSG) has been shown to have potential health-modulating uses. Based on the results of 16S rRNA sequencing and metabolomics analysis, NSG has the unique function of improving gut microbiota and inhibiting obesity. Specifically, NSG can enhance gut microbiota diversity and change their composition. A significant positive correlation exists between the liver change in lysine and the high-importance dominant species ([ Ruminococcus]_gnavus , Alistipes_finegoldii , etc.). NSG metabolites analysis showed that the lysine level increased by 44.45% and showed a significantly negatively correlated with (TG, TC, Leptin, etc.). Significantly, NSG reduces the degradation of lysine metabolism in the liver and inhibits fatty acid β-oxidation. In addition, NSG decreased Acetyl-CoA levels by 24% and regulated the downregulation of TCA genes (CS , Ogdh , Fh1 , and Mdh2) and the upregulation of ketone body production genes (BDH1). NSG may have a positive effect on obesity by reducing the participation of Acetyl-CoA in the TCA cycle pathway and enhancing the ketogenic conversion of Acetyl-CoA. In conclusion, the results of this study may provide a new dietary intervention strategy for preventing endocrine disruptor-induced obesity. [Display omitted] • Nanoselenium Siraitia grosvenorii reshapes gut microbiota disrupted by imidacloprid. • Liver lysine metabolism is linked to obesity caused by endocrine disruptors. • Apigenin may regulate the contribution of acetyl coenzyme A to energy metabolism. • Nanoselenium Siraitia grosvenorii is a potential candidate for improving obesity. [ABSTRACT FROM AUTHOR]

Background: Inhibition of indolamine-2,3-dioxygenase 1 (IDO1) has been proposed as a promising strategy for cancer immunotherapy; however, it has failed in clinical trials. Macrophages in the tumor microenvironment (TME) contribute to immune escape and serve as potential therapeutic targets. This study investigated the expression pattern of IDO1 in TME and its impact on prognosis and therapeutic response of patients with esophageal squamous cell carcinoma (ESCC)., Methods: RNA sequencing data from 95 patients with ESCC from The Cancer Genome Atlas (TCGA) database were used to explore the prognostic value of IDO1. Bioinformatics tools were used to estimate scores for stromal and immune cells in tumour tissues, abundance of eight immune cell types in TME, and sensitivity of chemotherapeutic drugs and immune checkpoint (IC) blockage. The results were validated using digitalized immunohistochemistry and multiplexed immunofluorescence in ESCC tissue samples obtained from our clinical center., Results: TCGA and validation data suggested that high expression of IDO1 was associated with poor patient survival, and IDO1 was an independent prognostic factor. IDO1 expression positively correlated with macrophages in TME and PDCD1 within diverse IC genes. Single-cell RNA sequencing data analysis and multiplexed immunofluorescence verified the coexpression of IDO1 and PD-1 in tumor-associated macrophages (TAMs). Patients with high IDO1 expression showed increased sensitivity to various chemotherapeutic drugs, while were more likely to resist IC blockage., Conclusion: This study identifies IDO1 as an independent prognostic indicator of OS in patients with ESCC, reveals a compelling connection of IDO1, PD-1, and TAMs, and explores the sensitivity of patients with high IDO1 expression to chemotherapeutic drugs and their resistance to IC blockade. These findings open new avenues for potential targets in ESCC immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Peng, Wang, Yang, Wu, Sun, Zhang, Yu, Zhang, Gao, Zhou, Zhu and Yin.)

The unique flavors of fermented foods significantly influence consumer purchasing choices, prompting widespread scientific interest in the flavor development process. Fermented rice and wheat foods are known for their unique flavors and they occupy an important place in the global diet. Many of these are produced on an industrial scale using starter cultures, whereas others rely on spontaneous fermentation, homemade production, or traditional activities. Microorganisms are key in shaping the sensory properties of fermented products through different metabolic pathways, thus earning the title "the essence of fermentation." Therefore, this study systematically summarizes the key microbial communities and their interactions that contribute positively to iconic fermented rice and wheat foods, such as steamed bread, bread, Mifen, and rice wine. This study revealed the mechanism by which these core microbial communities affect flavor and revealed the strategies of core microorganisms and related enzymes to enhance flavor during fermentation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. We confirm that there are no financial, personal, or professional interests that could potentially bias our research findings or influence the interpretation of the results presented in the manuscript. Additionally, we have not received any financial support, grants, or other forms of compensation that could be perceived as influencing the objectivity of our research. Furthermore, we declare that there are no relationships or affiliations with any organizations, companies, or individuals that could pose a conflict of interest for the content of the manuscript. We affirm that this Declaration of Interest accurately reflects our commitment to transparency and integrity in research, and we stand by the authenticity and impartiality of the findings reported in the manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: The purpose of this study was to explore the relationships among perceptions of decent work, psychological empowerment, and work immersion among nurses, hypothesizing that psychological empowerment mediates the relationship between perceptions of decent work and work immersion., Background: At present, there are many studies on nurses' perceptions of decent labor and work immersion in China, but the relationship between them has not been discussed from a psychological perspective., Methods: The sample consisted of clinical nurses in Jiangxi, Zhejiang, Hubei, and Guangdong provinces, China, and the nurses' general information, decent labor perception, psychological empowerment, and work immersion scores were assessed using the General Information Scale, Decent Labor Perception Scale, Psychological Empowerment Scale, and Work Immersion Scale, respectively. Pearson correlation analysis and structural equation modeling were used to analyze the data., Results: The total scores of nurses' perceptions of decent work, psychological empowerment, and work immersion were at a moderate level. The total nurse work immersion score and each dimension score were positively correlated with the total nurse decent work perception score and the total psychological empowerment score. Decent work perception and psychological empowerment directly and positively predicted work immersion; decent work perception also indirectly acted on work immersion through psychological empowerment., Conclusions and Implications for Nursing and Health Policy: Nurses' work immersion was moderate, and this study explored the mechanisms by which perceptions of decent work affect nurses' work immersion from a psychological perspective, validating the mediating role of psychological empowerment. This study emphasizes that nursing managers should fully understand the importance of nurses' work immersion, continuously improve nurses' decent labor perceptions, enhance their psychological empowerment level, improve their work immersion, and enhance the quality of nursing services., (© 2023 International Council of Nurses.)

Group-based trajectory modeling (GBTM) allows the trajectory analyses of repeated N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements during follow-up visits of pulmonary artery hypertension associated with connective tissue disease (CTD-PAH) patients. This study aimed to (1) identify trajectories of NT-proBNP changing over time, (2) explore the association between NT-proBNP trajectories and prognosis, and (3) explore the effects of baseline clinical characteristics on NT-proBNP trajectories. A retrospective, single-centred, observational study was performed on 52 CTD-PAH patients who had undergone at least three follow-up visits within 1 year from baseline. Four NT-proBNP trajectories were identified using GBTM: low stability ( n = 15, 28.85%), early remission (remission within 3 months) ( n = 20, 38.46%), delayed remission (remission after 6 or 9 months) ( n = 11, 21.15%), and high stability ( n = 6, 11.54%). The low-stability and early-remission trajectories were related to a similar positive prognosis, while the delayed-remission and high-stability trajectories were associated with a gradually worsening prognosis ( p = 0.000). Intensive CTD immunotherapy (corticosteroids plus immunosuppressants) was the only factor that remained significant after least absolute shrinkage and selection operator regression and multivariate logistic regression, and was independently associated with a lower risk NT-proBNP trajectory ( p = 0.048, odds ratio = 0.027, 95% confidence interval: 0.001-0.963), which preliminarily indicated a benefit of CTD-PAH patients undergoing intensive CTD immunotherapy.

The extensive application of pesticides and antibiotics in agricultural production makes it possible for them to coexist in farmland, and the interaction of the two pollutants can lead to changes in environmental behavior and toxicity, creating uncertainty risks to soil and soil organisms. In this study, we explored the environmental behavior and the effects of earthworms under co-exposure to amoxicillin and boscalid and further explored the accumulation and toxic effects on earthworms. The results showed that amoxicillin increased the adsorption of boscalid in soil and inhibited its degradation. In addition, we noticed that the co-exposure of amoxicillin and boscalid caused intestinal barrier damage, which increased the bioaccumulation of earthworms for boscalid and led to more severe oxidative stress and metabolic disorders in earthworms. In summary, our findings indicate that amoxicillin can increase the ecological risk of boscalid in the environment and imply that the encounter between antibiotics and pesticides in the environment can amplify the toxic effects of pesticides, which provides new insights into the ecological risks of antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The N6-methyladenosine (m 6 A) modification of RNA and its regulators have important roles in the pathogenesis of pulmonary hypertension (PH). Ythdf2 (YTH N6-methyladenosine RNA binding protein 2) is best known for its role in degrading m 6 A-modified mRNAs such as Hmox1 mRNA, which leads to alternative activation of macrophages in PH. Recent studies have also linked Ythdf2 to the proliferation of pulmonary artery smooth muscle cells (PASMCs). However, its specific roles in PASMCs and downstream targets during the development of PH remain unclear., Methods: The expression and biological function of Ythdf2 in PASMCs were investigated in human and experimental models of PH. Smooth muscle cell-specific Ythdf2 -deficient mice were used to assess the roles of Ythdf2 in PASMCs in vivo. Proteomic analysis, m 6 A sequencing, and RNA immunoprecipitation analysis were used to screen for potential downstream targets., Results: Ythdf2 was significantly upregulated in human and rodent PH-PASMCs, and smooth muscle cell-specific Ythdf2 deficiency ameliorated PASMC proliferation, right ventricular hypertrophy, pulmonary vascular remodeling, and PH development. Higher expression of Ythdf2 promoted PASMC proliferation and PH by paradoxically stabilizing Myadm mRNA in an m 6 A-dependent manner. Loss of Ythdf2 decreased the expression of Myadm in PASMCs and pulmonary arteries, both in vitro and in vivo. Additionally, silencing Myadm inhibited the Ythdf2 -dependent hyperproliferation of PASMCs by upregulating the cell cycle kinase inhibitor p21., Conclusions: We have identified a novel mechanism where the increased expression of Ythdf2 stimulates PH-PASMC proliferation through an m 6 A/Myadm/p21 pathway. Strategies targeting Ythdf2 in PASMCs might be useful additions to the therapeutic approach to PH., Competing Interests: None.

Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis., (© 2024. The Author(s).)

Synaptic dysfunction is a core component of the pathophysiology of schizophrenia. However, the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood. The Stonin 2 (STON2) gene encodes a major adaptor for clathrin-mediated endocytosis (CME) of synaptic vesicles. In this study, we showed that the C-C (307Pro-851Ala) haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME. We found that schizophrenia-related STON2 variations led to protein dephosphorylation, which affected its interaction with synaptotagmin 1 (Syt1), a calcium sensor protein located in the presynaptic membrane that is critical for CME. STON2 307Pro851Ala knockin mice exhibited deficits in synaptic transmission, short-term plasticity, and schizophrenia-like behaviors. Moreover, among seven antipsychotic drugs, patients with the C-C (307Pro-851Ala) haplotype responded better to haloperidol than did the T-A (307Ser-851Ser) carriers. The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2 307Pro851Ala knockin mice. Our findings demonstrated the effect of schizophrenia-related STON2 variations on synaptic dysfunction through the regulation of CME, which might be attractive therapeutic targets for treating schizophrenia-like phenotypes., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

The widespread use of cyproconazole (CPZ) enhances food security but may pose potential risks to non-target organisms. Therefore, we applied Multi-omics techniques to reveal the response of the intestinal barrier to CPZ exposure and explore whether the Bifidobacterium intervention experiment can repair the damage. First, we found that exposure to CPZ at environmentally relevant concentrations led to intestinal injury phenotype, significantly down-regulated intestinal protein gene expression, and up-regulated pro-inflammatory gene expression, further causing intestinal dysbacteriosis and metabolic disorders. In particular, by combining analysis of gut microbiota and metabolites, we noticed acetate, a key metabolite, which decreased sharply after exposure to high concentration of CPZ. Expectedly, after supplementing with Bifidobacterium (a core bacterium that produces acetate), we noticed that the acetate content was quickly restored. Further, we also verified that the increase in acetate content after Bifidobacterium supplementation at least partially promoted IL-22 secretion, which in turn stimulated the secretion of β-defensins (zfbd-1, zfbd-2, zfbd-3), thereby repairing the intestinal damage. In conclusion, our work confirms the potential of Bifidobacterium to improve intestinal damage and metabolic dysbiosis caused by CPZ exposure. It provides directional recommendations for the application of probiotics to repair the toxicological risk of pesticide exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that they could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To investigate the prognostic impact and pathophysiological characteristics of fragmented QRS complex (fQRS) on patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH)., Methods: This was a multicentre retrospective study recruiting 141 patients with CTD-PAH diagnosed by right heart catheterization (114 cases in the discovery cohort and 27 cases in the validation cohort). fQRS and ST-T change were detected on conventional 12-lead electrocardiogram (ECG). Patients were followed up every 3 months to update their status and the primary end point was all-cause death. Clinical information and ECG characteristics were compared between survival and death groups and Kaplan-Meier curve was used for survival analysis., Results: There were significant differences in age, gender, 6-min walk distance, NT-proBNP, WHO class, presence of fQRS and presence of ST-T change in inferior leads between survival group and death group. Inferior fQRS and ST-T change were significantly associated with right ventricular (RV) dilatation and reduced RV ejection fraction (RVEF). Kaplan-Meier curve showed that all-cause mortality was higher in CTD-PAH with fQRS (p= 0.003) and inferior ST-T change (p= 0.012). Low- and intermediate-risk CTD-PAH with inferior ST-T change had higher all-cause mortality (p= 0.005). The prognostic value of fQRS and inferior ST-T change was validated in external validation cohort., Conclusion: The presence of inferior fQRS and ST-T change could predict poor prognosis in CTD-PAH., Clinical Trial Registration Number: NCT05980728, https://clinicaltrials.gov., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

F-box proteins participate in the regulation of many processes, including cell division, development, and plant hormone responses. Brassinosteroids (BRs) regulate plant growth and development by activating core transcriptional and other multiple factors. In rice, OVATE family proteins (OFPs) participate in BR signalling and regulate grain size. Here we identified an F-box E3 ubiquitin ligase, FBX206, that acts as a negative factor in BR signalling and regulates grain size and yield in rice. Suppressed expression of FBX206 by RNAi leads to promoted plant growth and increased grain yield. Molecular analyses showed that the expression levels of BR biosynthetic genes were up-regulated, whereas those of BR catabolic genes were down-regulated in FBX206-RNAi plants, resulting in the accumulation of 28-homoBL, one of the bioactive BRs. FBX206 interacted with OsOFP8, a positive regulator in BR signalling, and OsOFP19, a negative regulator in BR signalling. SCFFBX206 mediated the degradation of OsOFP8 but suppressed OsOFP19 degradation. OsOFP8 interacted with OsOFP19, and the reciprocal regulation between OsOFP8 and OsOFP19 required the presence of FBX206. FBX206 itself was ubiquitinated and degraded, but interactions of OsOFP8 and OsOFP19 synergistically suppressed the degradation of FBX206. Genetic interactions indicated an additive effect between FBX206 and OsOFP8 and epistatic effects of OsOFP19 on FBX206 and OsOFP8. Our study reveals the regulatory networks of FBX206, OsOFP8, and OsOFP19 in BR signalling that regulate grain size and yield in rice., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The extensive application of pesticides in agricultural production has raised significant concerns about its impact on human health. Different pesticides, including fungicides, insecticides, and herbicides, cause environmental pollution and health problems for non-target organisms. Infants and young children are so vulnerable to the harmful effects of pesticide exposure that early-life exposure to pesticides deserves focused attention. Recent research lays emphasis on understanding the mechanism between negative health impacts and early-life exposure to various pesticides. Studies have explored the impacts of exposure to these pesticides on model organisms (zebrafish, rats, and mice), as well as the mechanism of negative health effects, based on advanced methodologies like gut microbiota and multi-omics. These methodologies help comprehend the pathogenic mechanisms associated with early-life pesticide exposure. In addition to presenting health problems stemming from early-life exposure to pesticides and their pathogenic mechanisms, this review proposes expectations for future research. These proposals include focusing on identifying biomarkers that indicate early-life pesticide exposure, investigating transgenerational effects, and seeking effective treatments for diseases arising from such exposure. This review emphasizes how to understand the pathogenic mechanisms of early-life pesticide exposure through gut microbiota and multi-omics, as well as the adverse health effects of such exposure., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

In recent years, environmental DNA (eDNA) has received attention from biologists due to its sensitivity, convenience, labor and material efficiency, and lack of damage to organisms. The extensive application of eDNA has opened avenues for the monitoring and biodiversity assessment of amphibians, which are frequently small and difficult to observe in the field, in areas such as biodiversity survey assessment and detection of specific, rare and threatened, or alien invasive species. However, the accuracy of eDNA can be influenced by factors such as ambient temperature, pH, and false positives or false negatives, which makes eDNA an adjunctive tool rather than a replacement for traditional surveys. This review provides a concise overview of the eDNA method and its workflow, summarizes the differences between applying eDNA for detecting amphibians and other organisms, reviews the research progress in eDNA technology for amphibian monitoring, identifies factors influencing detection efficiency, and discusses the challenges and prospects of eDNA. It aims to serve as a reference for future research on the application of eDNA in amphibian detection., (© 2023 Wiley Periodicals LLC.)

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by core symptoms of impaired social interaction and communication. The pathological mechanism and treatment are not clear and need further study. Our previous study found that the deletion of high-risk gene Autism Susceptibility 2 (AUTS2) in mice led to dentate gyrus (DG) hypoplasia that highly associated with impaired social novelty recognition. Here we aim to improve the social deficit through increasing the neurogenesis in the subgranular zone (SGZ) and expanding the newborn granule neurons in DG., Methods: Three approaches including repeated oxytocin administration, feeding in enriched environment and overexpression of cyclin-dependent kinase 4 (Cdk4)-CyclinD1 complex in DG neural stem cells (NSCs) at the post-weaning stage were conducted., Results: We found that the number of EdU labeled proliferative NSCs or retrovirus labeled newborn neurons was significantly increased after manipulations. The social recognition deficit was also significantly improved., Discussion: Our findings suggested a possible strategy to restore the social deficit through expansion of newborn neurons in hippocampus, which might provide a new insight into the treatment of autism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Meng, Li, Wang, Yue, Zhang, Sun, Wang and Li.)

Pulmonary hypertension (PH) is a devastating disease characterized by irreversible pulmonary vascular remodeling (PVR) that causes right ventricular failure and death. The early alternative activation of macrophages is a critical event in the development of PVR and PH, but the underlying mechanisms remain elusive. Previously we have shown that N 6 -methyladenosine (m 6 A) modifications of RNA contribute to phenotypic switching of pulmonary artery smooth muscle cells and PH. In the current study, we identify Ythdf2, an m 6 A reader, as an important regulator of pulmonary inflammation and redox regulation in PH. In a mouse model of PH, the protein expression of Ythdf2 was increased in alveolar macrophages (AMs) during the early stages of hypoxia. Mice with a myeloid specific knockout of Ythdf2 (Ythdf2 Lyz2 Cre ) were protected from PH with attenuated right ventricular hypertrophy and PVR compared to control mice and this was accompanied by decreased macrophage polarization and oxidative stress. In the absence of Ythdf2, heme oxygenase 1 (Hmox1) mRNA and protein expression were significantly elevated in hypoxic AMs. Mechanistically, Ythdf2 promoted the degradation of Hmox1 mRNA in a m 6 A dependent manner. Furthermore, an inhibitor of Hmox1 promoted macrophage alternative activation, and reversed the protection from PH seen in Ythdf2 Lyz2 Cre mice under hypoxic exposure. Together, our data reveal a novel mechanism linking m 6 A RNA modification with changes in macrophage phenotype, inflammation and oxidative stress in PH, and identify Hmox1 as a downstream target of Ythdf2, suggesting that Ythdf2 may be a therapeutic target in PH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Dermatomyositis (DM) is an acquired autoimmune disease that can cause damage to various organs, including the heart muscle. However, the mechanisms underlying myocardial injury in DM are not yet fully understood., Methods: In this study, we utilized publicly available datasets from the Gene Expression Omnibus (GEO) database to identify hub-genes that are enriched in the immune system process in DM and myocarditis. Weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, protein-protein interaction (PPI), and gene ontology (GO) analysis were employed to identify these hub-genes. We then used the CIBERSORT method to analyze immune cell infiltration in skeletal muscle specimens of DM and myocardium specimens of myocarditis respectively. Correlation analysis was performed to investigate the relationship between key genes and infiltrating immune cells. Finally, we predicted regulatory miRNAs of hub-genes through miRNet and validated their expression in online datasets and clinical samples., Results: Using integrated bioinformatics analysis, we identified 10 and 5 hub-genes that were enriched in the immune system process in the database of DM and myocarditis respectively. The subsequent intersections between hub-genes were IFIT3, OAS3, ISG15, and RSAD2. We found M2 macrophages increased in DM and myocarditis compared to the healthy control, associating with the expression of IFIT3, OAS3, ISG15, and RSAD2 in DM and myocarditis positively. Gene function enrichment analysis (GSEA) showed that IFIT3, OAS3, ISG15, and RSAD2 were mainly enriched in type I interferon (IFN) signaling pathway, cellular response to type I interferon, and response to type I interferon. Finally, we verified that the expression of miR-146a-5p was significantly higher in the DM with myocardial injury than those without myocardial injury (p = 0.0009)., Conclusion: Our findings suggest that IFIT3, OAS3, ISG15, and RSAD2 may play crucial roles in the underlying mechanism of myocardial injury in DM. Serum miR-146a-5p could be a potential biomarker for myocardial injury in DM., (© 2023. The Author(s).)

Longan yield estimation is an important practice before longan harvests. Statistical longan yield data can provide an important reference for market pricing and improving harvest efficiency and can directly determine the economic benefits of longan orchards. At present, the statistical work concerning longan yields requires high labor costs. Aiming at the task of longan yield estimation, combined with deep learning and regression analysis technology, this study proposed a method to calculate longan yield in complex natural environment. First, a UAV was used to collect video images of a longan canopy at the mature stage. Second, the CF-YD model and SF-YD model were constructed to identify Cluster_Fruits and Single_Fruits, respectively, realizing the task of automatically identifying the number of targets directly from images. Finally, according to the sample data collected from real orchards, a regression analysis was carried out on the target quantity detected by the model and the real target quantity, and estimation models were constructed for determining the Cluster_Fruits on a single longan tree and the Single_Fruits on a single Cluster_Fruit. Then, an error analysis was conducted on the data obtained from the manual counting process and the estimation model, and the average error rate regarding the number of Cluster_Fruits was 2.66%, while the average error rate regarding the number of Single_Fruits was 2.99%. The results show that the method proposed in this paper is effective at estimating longan yields and can provide guidance for improving the efficiency of longan fruit harvests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Sun, Jia, Yao, Lin, Chen, Zhou, Zhou, Wu, Shi and Li.)

In this work, a colorimetric biosensor based on the rapid color change of Escherichia coli DH 5α (E. coli) and p-benzoquinone (BQ) was introduced to evaluate water toxicity. Here, dark brown quinhydroquinone (QHQ) was obtained from the reaction between E. coli and BQ. The inhibition ratios were calculated by RGB (red, green, blue) values of samples or oxidation current of hydroquinone (HQ). Here, RGB technology was used for biotoxicity assessment for the first time. The results suggested that the biosensor-based RGB has an obvious dose-dependent response. The IC 20 values of Hg 2+ and Cu 2+ obtained based on RGB values were 1.0 and 1.5 mg L -1 , respectively. This biosensor can be used to detect quickly toxicity of the Cu 2+ and Hg 2+ in water without complicated operation steps. Therefore, the biosensor has potential application value in the field of water toxicity detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Solar-to-fuel conversion followed by secondary utilization in fuel cells provides an appealing approach to alleviating global energy shortages but is largely restricted by the complex design of power systems and the development of functional catalysts. Herein, we presented a biohybrid photoelectrochemical cell (BPEC) to implement sustainable solar-to-fuel-to-electric power conversion in a single compartment, by ingeniously combining reliable photoelectrochemical H 2 O 2 generation with efficient bioelectrochemical H 2 O 2 consumption. Specifically, the BPEC is composed of a Mo-modified BiVO 4 (Mo:BiVO 4 ) photoanode and a horseradish peroxidase (HRP)/pyrene-modified 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (bis-Pyr-ABTS)/carbon nanotubes with an encapsulated Co nanoparticle (Co/CNTs) biocathode. Upon photoexcitation, two-electron H 2 O oxidation can be carried out at the Mo-BiVO 4 photoanode to produce H 2 O 2 , followed by electroenzymatic reduction of H 2 O 2 to H 2 O by HRP with the help of a bis-Pyr-ABTS redox mediator at the biocathode. Besides, in response to the insufficient Faradaic efficiency of H 2 O 2 generation at the photoanode, the functional Co/CNTs catalysts, possessing prominent electrocatalytic selectivity toward two-electron O 2 reduction (electron transfer number = 2.6), are modified on the biocathode, thus clearly defining effective H 2 O/H 2 O 2 /O 2 self-circulation in this device. This developed BPEC obtains an open-circuit potential of 1.03 ± 0.02 V and a maximum power density of 0.18 ± 0.02 mW cm -2 . Moreover, inspired by the particular advantage of enzymatic biofuel cells for easy miniaturization, an enclosed "sandwich-like" BPEC of approximately 1 cm 3 size is fabricated and delivers a power output of 0.13 ± 0.03 mW cm -2 . Our work represents a controllable approach for meaningful solar energy utilization, beyond traditional artificial photosynthesis, and can further provide a significant paradigm shift in building an energy-sustainable society.

The radial migration of cortical pyramidal neurons (PNs) during corticogenesis is necessary for establishing a multilayered cerebral cortex. Neuronal migration defects are considered a critical etiology of neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia, epilepsy, and intellectual disability (ID). TRIO is a high-risk candidate gene for ASDs and ID. However, its role in embryonic radial migration and the etiology of ASDs and ID are not fully understood. In this study, we found that the in vivo conditional knockout or in utero knockout of Trio in excitatory precursors in the neocortex caused aberrant polarity and halted the migration of late-born PNs. Further investigation of the underlying mechanism revealed that the interaction of the Trio N-terminal SH3 domain with Myosin X mediated the adherence of migrating neurons to radial glial fibers through regulating the membrane location of neuronal cadherin (N-cadherin). Also, independent or synergistic overexpression of RAC1 and RHOA showed different phenotypic recoveries of the abnormal neuronal migration by affecting the morphological transition and/or the glial fiber-dependent locomotion. Taken together, our findings clarify a novel mechanism of Trio in regulating N-cadherin cell surface expression via the interaction of Myosin X with its N-terminal SH3 domain. These results suggest the vital roles of the guanine nucleotide exchange factor 1 (GEF1) and GEF2 domains in regulating radial migration by activating their Rho GTPase effectors in both distinct and cooperative manners, which might be associated with the abnormal phenotypes in neurodevelopmental disorders., (© 2021. The Author(s).)

Autism spectrum disorders (ASDs) are a group of highly inheritable neurodevelopmental disorders. Functional mutations in TRIO, especially in the GEF1 domain, are strongly implicated in ASDs, whereas the underlying neurobiological pathogenesis and molecular mechanisms remain to be clarified. Here we characterize the abnormal morphology and behavior of embryonic migratory interneurons (INs) upon Trio deficiency or GEF1 mutation in mice, which are mediated by the Trio GEF1-Rac1 activation and involved in SDF1α/CXCR4 signaling. In addition, the migration deficits are specifically associated with altered neural microcircuit, decreased inhibitory neurotransmission, and autism-like behaviors, which are reminiscent of some features observed in patients with ASDs. Furthermore, restoring the excitatory/inhibitory (E/I) imbalance via activation of GABA signaling rescues autism-like deficits. Our findings demonstrate a critical role of Trio GEF1 mediated signaling in IN migration and E/I balance, which are related to autism-related behavioral phenotypes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells. This study was to investigate the correlation of peripheral granzyme B (GranzB)-expressing CD4+ T cells with disease severity and histological lesion in patients with pSS., Methods: We recruited 116 pSS and 46 health control (HC) using flow cytometry to examine the percentage of CD4+GranzB+CTLs in the peripheral blood, and immunofluorescence to test their expression in the labial gland., Results: The percentage of CD4+GranzB+CTLs was significantly upregulated in pSS than in HC (7.1 ± 4.9% vs 3.1 ± 1.9%, p < 0.0001) and positive correlation with ESSDAI. The frequency of them was markedly higher in pSS with extraglandular manifestations. After excluding the other risk factors associated with pSS, they were still related to ESSDIA and extraglandular manifestations independently (p < 0.05), and they are the risk factor of extraglandular involvement (odds ratio = 1.928). Moreover, they could be observed in the LSGs. ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS and 0.851 to presume extraglandular manifestations. The best diagnostic cutoff point was 4.865 for pSS patients., Conclusion: In this study, we provide new evidence indicating the involvement of CD4+GranzB+CTLs over activation in the pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS., (© 2021. The Author(s).)

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca 2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca 2+ , Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y 12 receptors. D76 and D127 in P2Y 12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y 12 (D76/D127) → Giβγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs., Competing Interests: The authors declare no competing interest.

Background: Previous studies have shown that serum uric acid (UA) levels are correlated with the severity of idiopathic pulmonary arterial hypertension (IPAH) and are predictors of disease prognosis. Still, few studies have explored the value of serum UA in pulmonary arterial hypertension secondary to connective tissue disease (CTD-PAH). This retrospective study aimed to investigate the clinical value of serum UA levels in patients with CTD-PAH., Methods: Fifty CTD-PAH patients were enrolled in our study, from which baseline UA levels, respective variations, and additional clinical data were collected. The potential association between baseline UA level and severity of CTD-PAH was investigated. Furthermore, the relationship between baseline UA and survival rate of CTD-PAH patients, as well as between UA variations and survival rate of pulmonary hypertension secondary to connective tissue disease (CTD-PH) patients was discussed., Results: Baseline serum UA levels were positively correlated with pulmonary vascular resistance (PVR). During the follow-up period, 3 CTD-PAH and 12 CTD-PH patients died. Kaplan-Meier survival curves showed lower survival rate in patients with hyperuricemia than in patients with normouricemia, in both groups (CTD-PAH group p = 0.041, CTD-PH group p = 0.013). Concerning serum UA variations, patients with persistent hyperuricemia showed the lowest survival rate when compared with patients with steady normouricemia (p = 0.01) or patients with decresing serum UA levels, i.e. undergoing from a status of hyperuricemia to a status of normouricemia (p = 0.023)., Conclusion: Baseline serum UA levels might predict severity of CTD-PAH. Together with baseline values, changes of uric acid level may predict the clinical prognosis of the disease.

Secondary cell wall not only provides rigidity and mechanical resistance to plants, but also has a large impact on plant growth and adaptation to environments. Biosynthesis of secondary cell wall is regulated by a complicated signaling transduction network; however, it is still unclear how the transcriptional regulation of secondary cell wall biosynthesis works at the molecular level. Here, we report in rice that OVATE family proteins 6 (OsOFP6) is a positive regulator in modulating expression of the genes related to biosynthesis of the secondary cell wall. Transgenic plants with knock-down of OsOFP6 by RNA interference showed increased leaf angle, which resulted from the thinner secondary cell wall with reduced amounts of cellulose and lignin, whilst overexpression of OsOFP6 in rice led to the thinker secondary cell wall with increased lignin content. Protein-protein interaction analysis revealed that OsOFP6 interacts with Oryza sativa homeobox 15 (OSH15), a class I KNOX protein. The interaction of OsOFP6 and OSH15 enhanced the transcriptional activity of OSH15 which binds to the promoter of OsIRX9 (Oryza sativa IRREGULAR XYLEM 9). Taken together, our study provides insights into the function of OsOFP6 in regulating leaf angle and the control of biosynthesis of secondary cell wall.

Objective: To explore the long-term prognostic value of a simplified risk assessment strategy based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension (PH) guidelines in Chinese patients with connective tissue disease (CTD) associated with pulmonary arterial hypertension (PAH)., Methods: We identified 50 CTD-PAH patients diagnosed by right heart catheterization. A retrospective chart review was completed to assess their clinical presentation and laboratory test results. A simplified version of the risk stratification model proposed by the 2015 ESC/ERS PH guidelines was applied, which included the WHO functional class, the 6-minute walking distance test, N-terminal pro-B-type natriuretic peptide plasma levels, pericardial effusion, right atrial pressure (RAP), cardiac index (CI), and mixed venous oxygen saturation (SvO 2 ). The risk grades were defined as follows: low risk = at least 3 low-risk variables and no high-risk variables; high risk = at least 2 high-risk variables, including SvO 2 or CI; and intermediate risk = when the above definitions of low or high risk were not fulfilled. The study endpoint was 3-year all-cause mortality., Results: Twenty patients were defined as a low-risk group, while 30 were classified into a combined intermediate-high-risk group at the baseline assessment. All 20 patients in the low-risk group remained in the low-risk group at follow-up, 20 patients in the intermediate-high-risk group were downgraded to the low-risk group, and eight patients remained in the intermediate-high-risk group at the follow-up assessment. Patients in the intermediate-high-risk group exhibited higher 3-year mortality than the low-risk group at baseline (26% vs 14%, P = 0.0384). Compared with patients who remained in the intermediate-high-risk group, patients who were downgraded to the low-risk group showed lower 3-year mortality (P = 0.0281)., Conclusion: A simplified risk stratification model based on the 2015 ESC/ERS PH guidelines helped to identify CTD-PAH patients with poor long-term  prognosis , which was useful in evaluating the severity and treatment response of patients with CTD-PAH.Key Point•This study showed that the simplified version of the 2015 ESC/ERS risk stratification model could help identify Chinese CTD-PAH patients with poor prognosis at diagnosis and after treatment initiation.

Background: Dexamethasone (DEX) is an effective therapeutic option commonly used in the treatment of many inflammatory diseases. However, DEX could impair proliferation or differentiation of osteoblasts, suggesting a pivotal role of DEX in bone destruction., Objective: To investigate whether intraarticular injection of DEX could exacerbate bone erosion during CIA development., Setting: Collagen-induced arthritis (CIA) mice were divided into PBS-treated and DEX-treated groups (n = 5/group). Negative control group: DBA/1 mice (n = 5) were used as age-matched, healthy, untreated controls., Method: CIA was induced in male DBA/1 mice. Intraarticular injected DEX (0.01 mg/Kg, 10 μl) into the knee joint of CIA on Day 28, Day 35, Day 42 and Day 49 post the 1st immunization., Results: The severity of the arthritic disease was ameliorated in DEX-treated mice, accompanied by the decreased expression of IL-6, IL-8 and TNF-α. However, DEX treatment accelerates bone erosion and osteoporosis during CIA development and triggers higher expression of RANKL, IL-17 in vitro and vivo., Main Outcome Measure: The effect of DEX on bone structure was analyzed using Haematoxylin & Eosin (H&E) staining and Micro-CT. The levels of receptor activator for nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) were investigated by real-time PCR, Western Blot and immunohistochemical analysis. RASFs were stimulated with Interleukin (IL)-1β and then treated with different concentrations of DEX for 72 h., Conclusion: Intraarticular injection of DEX could exacerbate bone erosion in CIA model via up-regulation of RANKL expression.