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Bone marrow is pivotal for normal hematopoiesis and immune responses, yet it is often compromised by malignancies. The bone microenvironment (BME), composed of bone and immune cells, maintains skeletal integrity and blood production. The emergence of primary or metastatic tumors in the skeletal system results in severe complications and contributes significantly to cancer-related mortality. These tumors set off a series of interactions among cancer, bone, and immune cells, and disrupt the BME locally or distantly. However, the drivers, participants, and underlying molecules of these interactions are not fully understood. This review explores the crosstalk between bone metabolism and immune responses, synthesizing current knowledge on the intersection of cancer and osteoimmune biology. It outlines how bone marrow immune cells can either facilitate or hinder tumor progression by interacting with bone cells and pinpoints the molecules responsible for immunosuppression within bone tumors. Moreover, it discusses how primary tumors remotely alter the BME, leading to systemic immune suppression in cancer patients. This knowledge provides critical rationales for emerging immunotherapies in the treatment of bone-related tumors. Taken together, by summarizing the intricate relationship between tumor cells and the BME, this review aims to deepen the understanding of the diversity, complexity, and dynamics at play during bone tumor progression. Ultimately, it highlights the potential of targeting bone-tumor interactions to correct aberrant immune functions, thereby inhibiting tumor growth and metastasis.

Abstract Background Clinical nurses play a vital role in healthcare. Their innovative behavior is crucial for improving patient care, advancing the profession, and ensuring the healthcare industry’s continued success. Many studies have highlighted the importance of nurse innovative behavior, but the link between their innovative behavior, structural empowerment, and decent work perception remains unclear. Objectives This study aimed to investigate the relationship between innovative behavior, structural empowerment, and decent work perception among the Chinese clinical nurses and identify the mediating role of decent work perception. Methods A cross-sectional correlational design was employed, and from July 2023 to April 2024, 1,513 clinical nurses were recruited from 8 tertiary grade-A hospitals across three cities in China. Data from the Demographic Characteristics Questionnaire, the Nurse Innovation Behavior Scale, the Conditions of Work Effectiveness Questionnaire-II, and the Decent Work Perception Scale were collected through convenience sampling and analyzed using descriptive statistics, univariate correlation, and process plug-in mediation effect analyses. Results The total scores of innovative behavior, structural empowerment, and decent work perception were 28.36 ± 6.25, 51.15 ± 12.63, and 42.97 ± 9.25, respectively. Innovative behavior was significantly, moderately and positively correlated with structural empowerment (r = 0.657, p

Abstract Background Excessive oxidative stress is known to cause endothelial dysfunction and drive cardiovascular diseases (CVD). While telomerase reverse transcriptase (TERT) shows protective effects against oxidative stress in rodents and is associated to human flow-mediated dilation in CVD, its regulatory mechanisms in human vascular systems under pathological oxidative stress require further investigation. Methods Human induced pluripotent stem cells (hiPSCs) were used to create vascular organoids (VOs). These VOs and human umbilical vein endothelial cells (HUVECs) were subjected to oxidative stress through both hydrogen peroxide (H2O2) and oxidized low-density lipoprotein (oxLDL) models. The effects of TERT overexpression by inhibition of the ubiquitin protein ligase E3 component N-recognin 5 (UBR5) on reactive oxygen species (ROS)-induced vascular injury and cellular senescence were assessed using neovascular sprouting assays, senescence-associated β-galactosidase (SA-β-Gal) staining, and senescence-associated secretory phenotype (SASP) assays. Results ROS significantly impaired VO development and endothelial progenitor cell (EPC) angiogenesis, evidenced by reduced neovascular sprouting and increased senescence markers, including elevated SA-β-Gal activity and SASP-related cytokine levels. Overexpression of TERT counteracted these effects, restoring VO development and EPC function. Immunoprecipitation-mass spectrometry identified UBR5 as a critical TERT regulator, facilitating its degradation. Inhibition of UBR5 stabilized TERT, improving VO angiogenic capacity, and reducing SA-β-Gal activity and SASP cytokine levels. Conclusions Inhibiting UBR5 stabilizes TERT, which preserves EPC angiogenic capacity, reduces VO impairment, and delays endothelial cell senescence under oxidative stress. These findings highlight the potential of targeting UBR5 to enhance vascular health in oxidative stress-related conditions. Graphical Abstract

Abstract Globally, over 80% of wastewater is discharged into water bodies without adequate treatment (UNESCO 2017:10–15), making accurate water quality prediction essential for safeguarding aquatic ecosystems and public health. This study presents a novel QPSO-CNN-LSTM model that significantly advances water quality prediction by combining Quantum Particle Swarm Optimization (QPSO) with a CNN-LSTM architecture. Unlike traditional models, the QPSO-CNN-LSTM leverages CNN to capture complex spatial features from water quality data and LSTM to model long-term temporal dependencies. The QPSO algorithm optimizes key hyperparameters, mitigating the need for manual tuning and improving the model’s adaptability to dynamic environmental data. The model outperforms traditional methods with a 15–50% improvement in RMSE, MSE, MAE, and MAPE for dissolved oxygen and pH predictions. These enhancements demonstrate the model’s superior accuracy and robustness, making it an invaluable tool for real-time water quality monitoring, pollution prevention, and cost-effective water management strategies. The practical implications of this model offer a step forward in preserving aquatic ecosystems through data-driven environmental stewardship.

BackgroundDi(2-ethylhexyl) phthalate (DEHP) is the highest consumed and the most widely used phthalic acid ester, their effects on lipid metabolism have attracted the attention of many scholars. However, the associated mechanism is still unclear.ObjectiveTo observe the effect of DEHP on lipid metabolism in rats, probe its possible mechanism, and provide a research basis for the effect of DEHP on human lipid metabolism.MethodsForty healthy male SD rats were randomly divided into 4 groups: solvent control (0 mg·kg−1 DEHP), low DEHP (187 mg·kg−1), medium DEHP (375 mg·kg−1), and high DEHP (750 mg·kg−1) groups. DEHP was administered by oral gavage for 6 d per week, consecutively 8 weeks. The rats were weighed once a week during the exposure period. At 24 h after the last exposure, the rats were anesthetized with 20% urethane and sacrificed by apical puncture. Rat livers were harvested and weighed before hematoxylin-eosin (HE) histopathological observation. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of lipid metabolism-related genes Janus kinase 3 (JAK3), signal transducer and activator of transcription 5b (STAT5b), and peroxisome proliferator-activated receptor γ (PPARγ) in liver, and Western blot was used to detect the expression levels of lipid metabolism-related proteins JAK3, STAT5b, and PPARγ in liver.ResultsCompared with the control group, there was no significant difference in the body weight gain of the rats in each group (P>0.05). The liver organ coefficients of the DEHP exposure groups were higher than that of the control group (P

Aims: This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Methods: Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes. Results: WGCNA revealed critical gene modules for OB and OP, identifying the Toll-like receptor (TLR) signalling pathway as a common factor. TLR2 was the most significant gene, with a pronounced expression in macrophages. Elevated TLR2 expression correlated with increased adipose accumulation, inflammation, and osteoclast differentiation, linking it to OP development. Conclusion: Our study underscores the pivotal role of TLR2 in connecting OP and OB. It highlights the influence of TLR2 in macrophages, driving both diseases through a pro-inflammatory mechanism. These insights propose TLR2 as a potential dual therapeutic target for treating OP and OB. Cite this article: Bone Joint Res 2024;13(10):573–587.

Primula medogensis W.B Ju, B. Xu & X.F. Gao 2023, a new species categorized under P. sect. Cordifoliae, was officially described in 2023. Given its recent classification, the genetic resources for this species are currently very limited. Here, we sequenced and assembled the first complete chloroplast genome of P. medogensis using Illumina sequencing technology. The complete chloroplast genome of P. medogensis is 151,486 bp in length, exhibiting a typical quadripartite structure. It consists of a large single-copy region (LSC; 83,407 bp) and a small single-copy region (SSC;17675 bp), separated by a pair of inverted repeat regions (IRs; 25202 bp). A total of 131 genes were annotated, including 86 protein-coding, 37 tRNA, and eight rRNA genes. The overall GC content was 37.1%. Phylogenetic analysis of 59 Primula species revealed a close relationship between P. medogensis and P. calliantha subsp. bryophila.

Abstract The purpose of this study was to explore the correlation between Hashimoto’s thyroiditis and Metabolic dysfunction-associated fatty liver disease (MAFLD), and at the same time to screen high-risk groups for liver fibrosis in MAFLD, find out the high-risk related indicators. The physical examination population was included as the study subjects and was grouped according to the diagnostic criteria for MAFLD. APRI > 1 or NFS > 0.676 or FIB-4 > 2.67were used to assess people at high risk of liver fibrosis, and logistic regression analysis was used to identify risk factors associated with high risk of liver fibrosis in MAFLD. ROC curves are used to look for indicators of diagnostic value. The proportion of people with Hashimoto’s thyroiditis was lower in the MAFLD group. The MAFLD high-risk group for liver fibrosis had higher TSH levels, lower FT3 and FT4 levels, higher TGAB levels, and differences in biochemical markers. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients. ROC curve analysis showed that the AUC of age was 0.741 (0.721–0.761), and the optimal stage value was 57.5 years, while the AUC of AST was 0.729 (0.707–0.751), and the optimal cut-off value was 39.5 U/L. Age, BMI, FBG, and AST are risk factors for the high risk of liver fibrosis in MAFLD patients.The age is greater than or equal to 57.5 years, or the AST is greater than or equal to 39.5 U/L, indicating that the MAFLD patients are at high risk of liver fibrosis.

Abstract Background Post-stroke cognitive impairment (PSCI) not only increases patient mortality and disability, but also adversely affects motor function and the ability to perform routine daily activities. Current therapeutic approaches for, PSCI lack specificity, primarily relying on and medication and traditional cognitive therapy supplemented by a limited array of tools. Both transcranial direct current stimulation (tDCS) and virtual reality (VR) training have demonstrated efficacy in improving cognitive performance among PSCI patients. Previous findings across various conditions suggest that implementing a therapeutic protocol combining tDCS and VR (tDCS - VR) may yield superior in isolation. Despite this, to our knowledge, no clinical investigation combining tDCS and VR for PSCI rehabilitation has been conducted. Thus, the purpose of this study is to explore the effects of tDCS - VR on PSCI rehabilitation. Methods This 4-week, single-center randomized clinical trial protocol will recruit 200 patients who were randomly assigned to one of four groups: Group A (tDCS + VR), Group B (tDCS + sham VR), Group C (sham tDCS + VR), Group D (sham tDCS + sham VR). All four groups will receive conventional cognitive rehabilitation training. The primary outcome measurement utilizes the Mini-Mental State Examination (MMSE). Secondary outcome measures include the Montreal Cognitive Assessment, Frontal Assessment Battery, Clock Drawing Test, Digital Span Test, Logic Memory Test, and Modified Barthel Index. Additionally, S-YYZ-01 apparatus for diagnosis and treating language disorders assesses subjects’ speech function. Pre- and post-four-week intervention assessments are conducted for all outcome measures. Functional near-infrared spectroscopy (fNIRS) is employed to observe changes in oxygenated hemoglobin (HbO), deoxy-hemoglobin (HbR), and total hemoglobin (HbT) in the cerebral cortex. Discussion Our hypothesis posits that the tDCS - VR therapy, in opposed to individual tDCS or VR interventions, could enhance cognitive function, speech ability and daily living skills in PSCI patients while concurrently augmenting frontal cortical activity. This randomized study aims to provide a robust theoretical foundation supported by scientific evidence for the practical implementation of the tDCS - VR combination as a secure and efficient PSCI rehabilitation approach. Trial registration Chictr.org.cn Identifier: ChiCTR2300070580. Registered on 17th April 2023.

Objective: To explore whether thrombopoietin can exert a protective effect against doxorubicin-induced cardiotoxicity by modulating the sirtuin 1 (SIRT1) signaling pathway. Methods: H9c2 cell viability was determined by CCK-8 and cardiomyocyte apoptosis was detected by TUNEL assay. The protein expressions of SIRT1 and p38 MAPK were measured by Western blot. RT-qPCR was also used to determine S1RT1 mRNA expression. In addition, intracellular reactive oxygen species levels and antioxidant enzyme activities were evaluated. Results: Thrombopoietin treatment reversed doxorubicin-induced decline in H9c2 cell viability. It also increased SIRT1 and decreased p-p38 MAPK protein expressions. In addition, thrombopoietin significantly attenuated doxorubicin-induced apoptosis and oxidative stress, and enhanced antioxidant enzyme activities. However, silencing S1RT1 abrogated the protective effects of thrombopoietin, as evidenced by reduced cell viability and increased oxidative stress and reactive oxygen species levels. Conclusions: Thrombopoietin alleviates doxorubicin-induced cardiomyocyte injury by reducing oxidative stress and apoptosis via the SIRT1/p38 MAPK pathway. However, its protective effects need to be further verified in animal tests.

Abstract The growing prevalence of mental health issues underscores the need for innovative screening methods. Large-scale, internet-based psychological screening has emerged as a vital tool to accurately determine morbidity rates and facilitate early diagnosis of mental disorders. However, conventional psychological screening methods often struggle with non-genuine responses and lack objective metrics. To bridge this gap, we have compiled a novel dataset derived from an expansive screening initiative at Xinxiang Medical University. The study, conducted from February 27 to March 17, 2021, yielded a dataset comprising responses from 24,292 students to four well-established psychological scales—PHQ-9, GAD-7, ISI, and PSS. A distinctive feature of this dataset is the inclusion of response time data, which captures the temporal dynamics of participants’ interactions with the scales, offering valuable insights into their response behaviour. The release of this dataset offers a substantial opportunity for researchers in the domains of psychology and public health to explore new insights into mental health, scale reliability, and the dynamics of psychological assessment.

Abstract The best available technology (BAT) for waste plastics relies on their components and the right technology employed, while the quality of waste plastics depends on the original plastics and the source separation processes simultaneously. In this study, the quality of waste plastics and the potential recycling processes, including recycling granulation, pyrolysis to oil, Green-RDF and incineration technology, were co-related from the economic and technical perspective. A database was established for waste plastic components, considering factors such as plastic fraction, waste composition, moisture content, and impurity rate. The corresponding environmental impacts for the typical resource processes were assessed by life cycle analysis (LCA) and cost–benefit analysis combined. It was found that around 23% ± 1% of waste plastics in residual waste had the resource potential if the stricter classification criteria of plastic wastes were adopted, such as the components, moisture content less than 5% or 8% and impurity rate less than 8%. Pyrolysis to oil had the best environmental benefits in GWP100, reaching -1,683.51 kg CO2 equivalent (CO2-eq), determined as the best method for high-value plastics, and incineration depicted poor environmental benefits for low-value plastics. The net income of recycling granulation for middle-value waste plastics would achieve 1383 ± 35 yuan/ton through cost–benefit analysis, which represented the optimal economic benefits. CO2 emissions for waste plastics could be mitigated around 29.74% by matching BATs compared to the current management system, which would provide policymakers with proper recommendations in terms of the adaptability of waste plastic sources and technologies.

Abstract Ginsenoside Rb1 exhibits a wide range of biological activities, and gut microbiota is considered the main metabolic site for Rb1. However, the impact of gut microbiota on the pharmacokinetics of Rb1 are still uncertain. In this study, we investigated the gut microbiome changes and the pharmacokinetics after a 30 d Rb1 intervention. Results reveal that the systemic exposure and metabolic clearance rate of Rb1 and Rd were substantially affected after orally supplementing Rb1 (60 mg/kg) to rats. Significant increase in the relative abundance of Bacteroides cellulosilyticus in gut microbiota and specific glycoside hydrolase (GH) families, such as GH2, GH92, and GH20 were observed based on microbiome and metagenomic analysis. Moreover, a robust association was identified between the pharmacokinetic parameters of Rb1 and the relative abundance of specific Bacteroides species, and glycoside hydrolase families. Our study demonstrates that Rb1 administration significantly affects the gut microbiome, revealing a complex relationship between B. cellulosilyticus, key GH families, and Rb1 pharmacokinetics.

Non-alcoholic fatty liver disease (NAFLD), a type of liver disease for which no treatment is currently approved, remains a major concern worldwide. It is manifested as simple hepatocyte steatosis and can develop into inflammation, fibrosis, cirrhosis and liver cancer in severe cases. However, due to the lack of appropriate in vitro drug testing platforms, an in-depth understanding of the therapeutic activity of ginsenoside Rb1 in NAFLD remains challenging. Here, we proposed a NAFLD model on a liver organoids (LOs)-on-a-chip platform to evaluate the therapeutic effect of ginsenoside Rb1 in a dynamic, multi-condition and high-throughput manner. This platform allowed us to reshape certain features such as multicellular types and liver-specific functions of the physiology of the human-relative liver. Free fatty acids (FFAs)-induced LOs displayed typical pathological characteristics of NAFLD progression, including steatosis, oxidative stress, lipid peroxidation, inflammation and fibrosis. With ginsenoside Rb1 intervention, these pathological features can be significantly improved, which may provide new insights into the potential mechanisms of NAFLD progression and treatment and suggest the clinical implications for humans. The proposed system enables the formation, differentiation, and function of LOs to serve as a scalable, high-throughput and sensitive drug testing model, to potentially expedite the NAFLD drug discovery.

The permeability of coal reservoirs is affected by its inherent properties, temperature, stress state, etc. Taking the 13-1 coal seam of Huainan Liuzhuang Coal Mine as the research object, the variation of CH4 permeability under the coupling of volume stress, temperature and gas pressure, and under cyclic confining pressure were studied based on the CH4 permeability test. The results show that the CH4 permeability of coal affected by the coupling of volume stress and gas pressure mainly controlled by the effective stress, and the greater the effective stress is, the lower the permeability is. The effect of gas pressure on CH4 permeability is limited by volume stress, but gas pressure has a greater effect on CH4 permeability than volume stress. The influence of temperature and gas pressure coupling on CH4 permeability is dominated by gas pressure. Permeability decreases with the increase of gas pressure showing a type of “U slide”, and the “slide” change is more obvious than the “U” change. The influence of gas pressure on CH4 permeability is greater than that of temperature, and the increasing gas pressure will reduce the influence of temperature on permeability. The cyclic confining pressure will cause irreversible plastic deformation of the pore fractures, which reduces effective seepage channels in the coal and decreases CH4 permeability. The plastic deformation produced by the first cyclic confining pressure is the largest, and the amount of plastic deformation gradually decreases with the increase of the number of cycles.

Abstract Objective This study aimed to develop a novel scoring system utilizing circulating interleukin (IL) levels to predict resistance to intravenous immunoglobulin (IVIG) in Chinese patients with Kawasaki disease (KD). We further compared this scoring system against six previously established scoring methods to evaluate its predictive performance. Methods A retrospective analysis was conducted on KD patients who were treated at the cardiovascular medical ward of our institution from January 2020 to December 2022. Six scoring systems (Egami, Formosa, Harada, Kobayashi, Lan and Yang) were analyzed, and a new scoring system was developed based on our data. Results In our study, 521 KD patients were recruited, 42 of whom (8.06%) were identified as resistant to IVIG. Our study indicated that IVIG-resistant KD patients were at an increased risk for the development of coronary arterial lesions (CALs) (P = 0.001). The evaluation of IVIG resistance using various scoring systems revealed differing levels of sensitivity and specificity, as follows: Egami (38.10% and 88.52%), Formosa (95.24% and 41.13%), Harada (78.57% and 43.22%), Kobayashi (66.67% and 74.95%), Lan (66.67% and 73.49%), and Yang (69.05% and 77.24%). Our novel scoring system utilizing sIL-2R demonstrated the highest sensitivity and specificity of 69.29% and 83.91%, respectively, and calibration curves indicated a favorable predictive accuracy of the model. Conclusion Our newly developed scoring system utilizing sIL-2R demonstrated superior predictive performance in identifying IVIG resistance among Chinese patients with KD.

Abstract Background The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC.

The STK11 gene mutation is a common genetic alteration in non-small cell lung cancer (NSCLC) and is significantly associated with poor responses to current immunotherapy regimens. Despite its prevalence, there is currently no established standard for front-line treatment in this subtype of NSCLC, underscoring the increasing need for personalized therapeutic strategies. In this report, we present a case of a patient with STK11-mutant NSCLC who was treated with first-line cadonilimab (10mg/kg) in combination with pemetrexed (500mg/m^2) plus carboplatin (AUC=5), resulting in a notable extension of progression-free survival (PFS). This case highlights the potential efficacy and feasibility of combining immunotherapy with chemotherapy in patients with STK11-mutant NSCLC. Additionally, we provide a review of recent advancements in research related to STK11 mutations in lung cancer as reported in the literature.

In the context of chronic hepatitis B virus (HBV) infection, the continuous replication of HBV within host hepatocytes is a characteristic feature. Rather than directly causing hepatocyte destruction, this replication leads to immune dysfunction and establishes a state of T-B immune tolerance. Successful clearance of the HBV virus is dependent on the close collaboration between humoral and cellular immunity. Humoral immunity, mediated by B-cell subpopulations, and cellular immunity, dominated by T-cell subpopulations show varying degrees of dysfunction during chronic hepatitis B (CHB). Notably, not all T- and B-cells produce positive immune responses. This review examine the most recent developments in the mutual regulation of T-B cells during chronic HBV infection. Our focus is on the prevailing immunotherapeutic strategies, such as T cell engineering, HBV-related vaccines, PD-1 inhibitors, and Toll-like receptor agonists. While nucleos(t)ide analogues (NUCs) and interferons have notable limitations, including inadequate viral suppression, drug resistance, and adverse reactions, several HBV entry inhibitors have shown promising clinical efficacy. To overcome the challenges posed by NUCs or monotherapy, the combination of immunotherapy and novel antiviral agents presents a promising avenue for future CHB treatment and potential cure.

Recent advances in deep learning have brought new opportunities for analyzing land dynamics, and Recurrent Neural Networks (RNNs) presented great potential in predicting land-use and land-cover (LULC) changes by learning the transition rules from time series data. However, implementing RNNs for LULC prediction can be challenging due to the relatively short sequence length of multi-temporal LULC data, as well as a general lack of interpretability of deep learning models. To address these issues, we introduce a novel deep learning-based framework tailored for forecasting LULC changes. The proposed framework uniquely implements a cycle-consistent learning scheme on RNNs to enhance their capability of representation learning based on time-series LULC data. Moreover, a local surrogate approach is adopted to interpret the results of predicted instances. We tested the method in a LULC prediction task based on time-series Landsat data of Shenzhen, China. The experiment results indicate that the cycle-consistent learning scheme can bring substantial performance gains to RNN methods in terms of processing short-length sequence data. Also, the tests of interpretation methods confirmed the feasibility and effectiveness of adopting local surrogate models for identifying the influence of predictor variables on predicted urban expansion instances.

Pouteria caimito is a commercially valuable tropical fruit tree and has medicinal effects in Brazilian folklore. In this thesis, thirteen compounds were isolated for the first time from the fruit of P. caimito by ethanol extraction and various chromatographic column chromatography methods. The thirteen compounds were identified by NMR, HR-ESI-MS and various physicochemical data to contain nine triterpenoids. The results of activity screening experiments showed that compounds 2, 3 and 5 exhibited anti-inflammatory activity, while most of the triterpenoids exhibited anti-RSV, and anti-HSV activity to varying degrees. Based on these results, the content of compound 5 was determined due to its good pharmacological activity to be 13.3250 mg/kg in the fresh fruit. This study scientifically demonstrated the health benefits of consuming P. caimito fruits and also provided new ideas for further development and utilization of P. caimito. It not only has good potential as an anti-inflammatory or antiviral functional food but also can be considered a natural source of triterpenoids.

Based on the construction of digital technology evaluation index system, this paper builds a dynamic threshold regression model to explore the complex impact of digital technology on Chinese-style industrial modernization under the threshold of R&D human resources, taking 30 provinces as research objects. It has been found that China's digital technology index is continuously improving, but there is a digital gap among regions. The beneficial impact of digital technology on Chinese-style industrial modernization has been thoroughly validated. Considering the threshold effect of R&D human resources, the influence of digital technology on Chinese-style industrial modernization exhibits nonlinear characteristics. With R&D human resources crossing the first threshold, it has shown a significant positive effect on Chinese-style industrial modernization, and the middle range of R&D human resources presents the optimal interval of the relationship between the two. The research findings offer a theoretical framework for advancing the construction of Chinese-style modernization.

IntroductionThe impact of ocean acidification (OA) and nanoplastics (NPs) on harmful algal blooms (HAB) has emerged as a major global concern. However, the combined effects of OA and NPs on the HAB species are poorly understood.MethodsIn this study, dinoflagellate Prorocentrum donghaiense, a typical HAB species, was exposed to varying concentrations of NPs (108.15 ± 8.52 nm) (0, 5, 10, and 15 mg L−1) and CO2 (low CO2: 417 ppm, pH: 8.00 and high CO2: 1045 ppm, pH: 7.73) for seven days to investigate the combined effects of OA and NPs.Results and discussionThe findings revealed that NPs inhibited the growth of P. donghaiense by inducing oxidative stress, as indicated by elevated malondialdehyde (MDA) content and decreased carotenoid/chlorophyll-a ratio, even though photochemical efficiency (φP0, ψ0, and φE0), rETRmax and α were enhanced in response to NPs stress. However, OA promoted the growth and alleviated the adverse effects of NPs on P. donghaiense by increasing photochemical efficiency (φP0, ψ0, and φE0) and energy flux (RC/CS0, TR0/CS0, ET0/CS0) and enhancing the antioxidant ability (increased superoxide dismutase, and decreased MDA). P. donghaiense showed enhanced tolerance to NPs under simulated OA conditions. These findings enhance our knowledge of the HAB species response to NPs pollution under future OA scenarios.

IntroductionTuberculosis (TB) is a serious infectious disease that endangers human health, and TB becomes more difficult in eradiation due to its multidrug resistance (MDR). The objective of this research was to identify novel targets for treating TB.MethodsA 2-fold serial dilution method was used to determine minimal inhibitory concentrations (MIC) of compound M6 against Mycobacterium smegmatis (M. smegmatis). Compound M6 was subjected to reverse molecular docking with seven Mycobacterium tuberculosis proteins, and the best binding protein with the highest LibDock score was evaluated. The target protein with the highest score was purified through prokaryotic expression. Isolated target proteins were investigated for the enzyme activities and for the kinetic effect of compound M6 by absorbance detection. Subsequently, the CRISPR/Cas9 technology was employed to inhibit target gene expression for detecting MIC changes. Finally, potential targets were evaluated for the effect of the compound M6 in bacteria.ResultsThe MIC values of compound M6 against M. smegmatis were 32 μg/mL. The results from reverse molecular docking show that IspD has the highest LibDock score of 142.50, followed by Rv0674, IspF, and Dxr, with docking scores of 110.762, 71.6955, and 57.7446, respectively. IspD is a key enzyme in the 2-C-methyl-D-erythritol 4-phosphate pathway of MTB. The aKi and Ki values of M6 for the substrate MEP are 609.58 μM and 81.33 μM. For CTP, the aKi and Ki values are 657.89 μM and 40.07 μM. With tetracycline inducing CRISPR/Cas9 to suppress the expression of IspD, the MIC value of M6 against IspD went down significantly from 32 μg/mL to 4 μg/mL.ConclusionIspD is a novel target of the compound M6 for treating TB.

BackgroundRecently, a growing number of studies have specifically examined the impact of dietary variables on the development and progression of amyotrophic lateral sclerosis (ALS). The purpose of this study was to investigate the correlation between different dietary patterns and Chinese ALS patients’ prognosis.MethodsA retrospective study was conducted by recruiting 590 patients with ALS who attended and were regularly followed at hospitals in Nanjing from 2016 to 2023. Nutrient intake was calculated using dietary information collected through the food frequency questionnaire (FFQ), and patients were divided into a control group and special diet groups, including a high-calorie group (HC), a high-protein group (HP), and a ketogenic diet group (KD), based on their specific intake. And used the Kaplan-Meier product limiting distribution to compare the time required to transition between phases of different dietary patterns and to estimate cumulative survival probabilities.ResultsPatients in the HP had a better nutritional status. And the disease progression rate (ΔFS) was significantly associated with dietary patterns, with the KD group having the lowest ΔFS. Meanwhile, special diets extended the survival time of stage 4 patients but had no effect on the overall survival of the disease.ConclusionA special diet can be one of effective options for patients with advanced ALS. Patients with poor nutritional status may choose the HP diet, whereas those with underlying conditions should consider the ketogenic diet with caution.

Abstract Background and Aims Hepatocellular carcinoma (HCC) is a malignant tumour associated with high morbidity and mortality rates worldwide. Recently, TRPM8 was reported to play an important role in tumour progression. However, the precise role of TRPM8 in HCC remains unclear. In this study, we explored the expression levels, molecular functions and underlying mechanisms of TRPM8 in HCC. Methods Tissue samples were used to analyse the expression of TRPM8 to assess its diagnostic value for prognosis. Cell Counting Kit‐8, EdU and colony formation assays were performed to evaluate the effects of TRPM8 on cell proliferation, whereas the Transwell assay was used to assess cell migration and invasion. The role of TRPM8 in vivo was evaluated using a mouse subcutaneous xenograft tumour model. We performed PPI network analyses to understand the possible mechanisms of TRPM8 action. Results TRPM8 expression was decreased in HCC tissues and was correlated with histological grade and poor patient prognosis. Functionally, TRPM8 repressed the proliferation and metastasis of HCC cells both in vitro and in vivo by modulating the RTP3/STAT3 signalling pathway. Conclusion Our findings underscore the critical role of the TRPM8‐RTP3‐STAT3 axis in maintaining the malignant progression of HCC. Moreover, our study demonstrates that AD80 is involved in anti‐tumour processes by upregulating the expression of TRPM8.

Background Acute coronary syndrome and atrial fibrillation are common cardiovascular diseases in elderly individuals. Patients with comorbidities face increased risks of bleeding and ischemia; however, there is a lack of prognostic models for quantifying these risks in this special population. Methods and Results In this retrospective cohort study, 1851 patients (≥65 years old) with acute coronary syndrome and atrial fibrillation from 2 hospitals in China were included in the development cohort (1252 individuals) and 2 external validation cohorts (284 and 315 individuals). During 1‐year follow‐up, 96 Bleeding Academic Research Consortium type 3 or 5 bleeding events and 245 thromboembolic events were observed. In the development cohort, the concordance indexes for bleeding at 3, 6, and 12 mo ranged from 0.737 to 0.845 and for ischemia ranged from 0.723 to 0.777. The calibration curve and decision curve analysis indicated adequate calibration and clinical practicability. The concordance indexes varied from 0.679 to 0.809 in the validation cohorts. Subgroup analyses focusing on anticoagulant drugs and antithrombotic therapy were conducted, revealing similar discrimination and calibration. Kaplan–Meier curves demonstrated significant differences (log‐rank P

Understory plantation of cardamom (genus Amomum) is an ancient and widespread agroforestry practice in the eastern Himalayas and Southeast Asia, an area that supports high regional biodiversity. Cardamom provides an important cash income to rural people, and governments encourage cardamom cultivation as a replacement for slash-and-burn agriculture to alleviate poverty, aligning with the principles of the Globally Important Agricultural Heritage Systems (GIAHS) program initiated by the FAO. This program recognizes and supports traditional agricultural practices that contributes to biodiversity conservation and sustainable development. In this context, cardamom agroforestry not only supports local economies but also provides crucial habitat for animals, including the newly described skywalker hoolock gibbon (Hoolock tianxing). Nearly half of the remnant population of the skywalker hoolock gibbon lives in cardamom agroforest. In order to evaluate if gibbons could survive in cardamom agroforest for a relatively long term, we compared foraging behavior of gibbons over a year living in cardamom agroforests (group NA) and well-preserved forests (group BB) in Mt. Gaoligong, Yunnan, China. In response to habitat degradation caused by cardamom plantation, group NA increased feeding time and spent more time feeding on leaves. Notably, they consumed nuts of Castanopsis hystrix which is an unusual food type for gibbons. On the contrary, members of group BB rarely ate nuts though Castanopsis hystrix is abundant within its home range. However, group NA did not occupy a large home range, or travel longer in time or distance than group BB. We also monitored female reproduction of five groups for 5–13 years. Two adult females living in agroforests successfully reared two or three offspring with an inter-birth interval of five years. In addition, we surveyed group size of 16 groups (9 in agroforest vs. 7 in well preserved forests) from 2017 to 2023, and we found no significant difference in group size between habitats. Our results suggested that cardamom agroforest can sustain skywalker hoolock gibbons provided it is not too fragmented and hunting is prohibited.

Abstract Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated promising efficacy in early trials for relapsed/refractory diffuse large B cell lymphoma (DLBCL). However, its efficacy in treating primary refractory DLBCL has not been comprehensively investigated, and the underlying resistance mechanisms remain unclear. Here, we report the outcomes of a phase I, open-label, single-arm clinical trial of relmacabtagene autoleucel (relma-cel), a CD19-targeted CAR-T cell product, with safety and efficacy as primary endpoints. Among the 12 enrolled patients, 8 experienced grade 4 hematologic toxicity of treatment-emergent adverse event. No grade ≥3 cytokine release syndrome or neurotoxicity occurred. Single-cell RNA sequencing revealed an increase proportion of C1QB-expressing macrophages in patients with progressive disease before CAR-T cell therapy. Cholesterol efflux from M2 macrophages was found to inhibit CAR-T cells cytotoxicity by inducing an immunosuppressive state in CD8+ T cells, leading to their exhaustion. Possible interactions between macrophages and CD8+ T cells, mediating lipid metabolism (AFR1-FAS), immune checkpoint activation, and T cell exhaustion (LGALS9-HAVCR2, CD86-CTLA4, and NECTIN2-TIGIT) were enhanced during disease progression. These findings suggest that cholesterol efflux from macrophages may trigger CD8+ T cell exhaustion, providing a rationale for metabolic reprogramming to counteract CAR-T treatment failure. Chinadrugtrials.org.cn identifier: CTR20200376.

Objective In geothermal exploration, a clay cap is a typical hydrothermal geothermal system, and its depth and distribution range can provide crucial information for delineating the scope of geothermal resources and determining the location of geothermal drilling. Clay caps are usually composed of a clay layer formed through hydrothermal reactions and are characterized by low resistance. The low-resistivity cap can be effectively imaged using the audio-frequency magnetotelluric method. To obtain uncertainty information about the distribution of clay cap layers and imaging results, this paper employs the 1D trans-dimensional Bayesian inversion method to investigate the detection capabilities of low-resistance cap layers in geothermal areas through audio electromagnetic data. Methods In this paper, a model test is first carried out to establish a geoelectric model of a typical geothermal system.Subsequently, a 1D trans-dimensional Bayesian algorithm is used to invert the synthetic data to obtain the uncertainty information of the subsurface electrical structure and interface position. Then, the method was applied to the processing of measured audio frequency magnetotelluric data in the Yanggao geothermal area of Shanxi Province. Results This method has relatively accurate identification ability for low-resistivity clay caps, and the obtained uncertainty analysis results of the upper and lower interfaces of low-resistivity caps are also relatively reliable according to numerical tests. It was found that this method has a good ability to identify shallow low-resistivity caps and can provide an uncertainty evaluation of the clay cap interface position via field data tests. The 2D inversion results of this survey line verify the reliability of the 1D inversion. Conclusion This method has relatively accurate imaging capabilities and uncertainty analysis capabilities for shallow geothermal clay caprocks and has strong application prospects in geothermal detection.

Abstract MicroRNAs play an important role in the proliferation, invasion, and metastasis of malignancy. In previous studies (detailed in our previous paper), the expression of miR-6839-5p was significantly increased in SW1353 cells after 125I seed 6 Gy irradiation, which indicated miR-6839-5p may play a tumor suppression function in chondrosarcoma cells. This study aimed to identify the effects of miR-6839-5p on the human chondrosarcoma cells, and investigate the potential target genes of miR-6839-5p. Firstly, chondrosarcoma cells (SW1353 and CAL78) were transfected with hsa-miR-6839-5p specific mimic. Secondly, Cell viability assay (MTT assay), Colony formation assay, Wound healing assay, Transwell assay, TUNEL staining and Western blotting experiments were performed, and the results proved miR-6839-5p can inhibit chondrosarcoma cells proliferation, migration and invasion. Meanwhile, miR-6839-5p significantly down-regulated apoptosis facilitator Bcl-2 expression, and promoted apoptosis of chondrosarcoma cells. It is reasonable to speculate miR-6839-5p might downregulate Bcl-2 expression to induce apoptosis in SW1353 human chondrosarcoma cells. Lastly, RNA extraction and bioinformatic analysis was performed on SW1353 cells transfected with hsa-miR-6839-5p specific mimic to investigate the potential target genes of miR-6839-5p. A total of 253 differentially expressed mRNA genes (105 up-regulated genes and 148 down-regulated genes) were found, and 23 differentially expressed downregulated genes were identified. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the results, which demonstrated the expression of BST2, VEGFA, FPR3 and PPARA was significantly downregulated by miR-6839-5p mimic. Furthermore, miR-6839-5p inhibitor can restore or partially restore the expression value of the above four genes. The analysis results of miRNA target gene prediction database indicated VEGFA was the most likely direct target gene of miR-6839-5p.

Abstract Lithium‐ion batteries with fast-charging/discharging properties are urgently needed for the mass adoption of electric vehicles. Here, we show that fast charging/discharging, long-term stable and high energy charge-storage properties can be realized in an artificial electrode made from a mixed electronic/ionic conductor material (Fe/LixM, where M = O, F, S, N) enabled by a space charge principle. Particularly, the Fe/Li2O electrode is able to be charged/discharged to 126 mAh g−1 in 6 s at a high current density of up to 50 A g−1, and it also shows stable cycling performance for 30,000 cycles at a current density of 10 A g−1, with a mass-loading of ~2.5 mg cm−2 of the electrode materials. This study demonstrates the critical role of the space charge storage mechanism in advancing electrochemical energy storage and provides an unconventional perspective for designing high-performance anode materials for lithium-ion batteries.

Abstract Purpose Helicobacter pylori (H. pylori) infection has been reported to be associated with multiple metabolic diseases. However, the connection between H. pylori infection and gout has not been explored previously. Our study aimed to investigate the association of gout and H. pylori infection in hyperuricemia population in China. Patients and methods This cross-sectional study was performed among the subjects who underwent health checkup in our health promotion center from January 1, 2020 to December 31, 2021. A total of 53,629 subjects with a mean age of 44.2 years were included in this study. H. pylori infection was defined as a positive [13]C-urea breath test. The effect of H. pylori infection on gout was assessed by multiple logistic regression analysis. Results 720 subjects with gout and 15,077 subjects with asymptomatic hyperuricemia (> 420 µmol/L in male and > 360 µmol/L in female) were enrolled. The prevalence rates of H. pylori infection, hyperuricemia and gout were 26.3%, 29.5%, 1.3%, respectively. The prevalence rate of H. pylori infection was significantly higher in subjects with gout than in those with asymptomatic hyperuricemia (35.0% vs. 27.2%; P

Introduction Major depressive disorder (MDD), the second leading cause of disability globally, is considered to be associated with a consequent deterioration in the quality of life and can lead to a major economic burden on medical service and suicide-related costs. Previous research has shown that acupuncture may be beneficial for treating MDD. However, there is a lack of rigorous evidence from previous studies comparing acupuncture with antidepressant medications. This study aims to assess the therapeutic potential of acupuncture in the management of depressive disorders.Methods and analysis A multicentre, randomised, participant-blind, sham-controlled, 2×2 factorial clinical trial, Acupuncture and Escitalopram for Treating Major Depression Clinical Study, aims to compare the efficacy of acupuncture versus escitalopram in treating depression. This study will be conducted at three hospitals in China, enrolling 260 patients with moderate-to-severe major depression, as defined by DSM-5 criteria and Hamilton Depression Rating Scale (HDRS-17) Scores above 17. Participants will be randomly assigned in equal proportions to one of four groups (acupuncture/escitalopram, sham acupuncture/escitalopram, acupuncture/placebo and sham acupuncture/placebo) and undergo 30 sessions across 10 weeks. The primary outcome is change in HDRS-17 Score and secondary outcomes include BDI, Clinical Global Impression, Generalised Anxiety Disorder-7 and Mini-Mental State Examination Scores, alongside potential biological markers.Ethics and dissemination Ethical approval for the study was granted by the Ethics Committees of the Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine (2023-7th-HIRB-020), Shanghai Mental Health Centre (2022–86) and Shanghai Pudong New Area Hospital of Traditional Chinese Medicine (2023–003). Informed consent will be obtained from all participants. The study’s findings are intended for publication in a scholarly journal.Trial registration NCT05901571.

Summary: Tightly controlled neurogenesis is crucial for generating the precise number of neurons and establishing the intricate architecture of the cortex, with deficiencies often leading to neurodevelopmental disorders. Neuroepithelial progenitors (NPs) transit into radial glial progenitors (RGPs) to initiate neural differentiation, yet the governing mechanisms remain elusive. Here, we found that histone deacetylases 1 and 2 (HDAC1/2) mediated suppression of Wnt signaling is essential for the NP-to-RGP transition. Conditional depletion of HDAC1/2 from NPs upregulated Wnt signaling genes, impairing the transition to RGPs and resulting in rosette structures within the neocortex. Multi-omics analysis revealed that HDAC1/2 are critical for downregulating Wnt signaling, identifying Wnt9a as a key target. Overexpression of Wnt9a led to an increased population of NPs and the disruption of cortical organization. Notably, Wnt inhibitor administration partially rescued the disrupted cortical architecture. Our findings reveal the significance of tightly controlled Wnt signaling through epigenetic mechanisms in neocortical development.

Summary: The network approach to characterizing psychopathology departs from traditional latent categorical and dimensional approaches. Causal interplay among symptoms contributed to dynamic psychopathology system. Therefore, analyzing the symptom clusters is critical for understanding mental disorders. Furthermore, despite extensive research studying the topological features of symptom networks, the control relationships between symptoms remain largely unclear. Here, we present a novel systematizing concept, module control, to analyze the control principle of the symptom network at a module level. We introduce Module Control Network (MCN) to identify key modules that regulate the network’s behavior. By applying our approach to a multivariate psychological dataset, we discover that non-emotional modules, such as sleep-related and stress-related modules, are the primary controlling modules in the symptom network. Our findings indicate that module control can expose central symptom cluster governing psychopathology network, offering novel insights into the underlying mechanisms of mental disorders and individualized approach to psychological interventions.

Accurate wheat ear counting is one of the key indicators for wheat phenotyping. Convolutional neural network (CNN) algorithms for counting wheat have evolved into sophisticated tools, however because of the limitations of sensory fields, CNN is unable to simulate global context information, which has an impact on counting performance. In this study, we present a hybrid attention network (CTHNet) for wheat ear counting from RGB images that combines local features and global context information. On the one hand, to extract multi-scale local features, a convolutional neural network is built using the Cross Stage Partial framework. On the other hand, to acquire better global context information, tokenized image patches from convolutional neural network feature maps are encoded as input sequences using Pyramid Pooling Transformer. Then, the feature fusion module merges the local features with the global context information to significantly enhance the feature representation. The Global Wheat Head Detection Dataset and Wheat Ear Detection Dataset are used to assess the proposed model. There were 3.40 and 5.21 average absolute errors, respectively. The performance of the proposed model was significantly better than previous studies.

Objectives: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds. Methods: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. Results: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine). Conclusions: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

In order to accurately and quickly predict the coal seam gas occurrence and determine its control factors, the gas occurrence law of No.10 coal seam in Luling Coal Mine was analyzed by using the sub-source forecast method and fuzzy matter-element evaluation method. The evaluation of control factors of gas occurrence was carried out. The results show that the gas emission of No.10 coal seam is generally high, with the distribution characteristics of high in the central and western regions and low in the southeast. Its gas emission increases with the increase of depth, and the emission range is 9.23-16.11 m3/t. Applying control factor analysis, the study area is classified into three types of regions: the shallow area in southwest is considered as type I, and the deep area in northeast is predominantly considered as class II and III.

Abstract Background Ovarian cancer (OC) has the highest mortality rate among all gynecological malignancies. A hypoxic microenvironment is a common feature of solid tumors, including ovarian cancer, and an important driving factor of tumor cell survival and chemo- and radiotherapy resistance. Previous research identified the hypoxia-associated gene angiopoietin-like 4 (ANGPTL4) as both a pro-angiogenic and pro-metastatic factor in tumors. Hence, this work aimed to further elucidate the contribution of ANGPTL4 to OC progression. Methods The expression of hypoxia-associated ANGPTL4 in human ovarian cancer was examined by bioinformatics analysis of TCGA and GEO datasets. The CIBERSORT tool was used to analyze the distribution of tumor-infiltrating immune cells in ovarian cancer cases in TCGA. The effect of ANGPTL4 silencing and overexpression on the proliferation and migration of OVCAR3 and A2780 OC cells was studied in vitro, using CCK-8, colony formation, and Transwell assays, and in vivo, through subcutaneous tumorigenesis assays in nude mice. GO enrichment analysis and WGCNA were performed to explore biological processes and genetic networks associated with ANGPTL4. The results obtained were corroborated in OC cells in vitro by western blotting. Results Screening of hypoxia-associated genes in OC-related TCGA and GEO datasets revealed a significant negative association between ANGPTL4 expression and patient survival. Based on CIBERSORT analysis, differential representation of 14 distinct tumor-infiltrating immune cell types was detected between low- and high-risk patient groups. Silencing of ANGPTL4 inhibited OVCAR3 and A2780 cell proliferation and migration in vitro and reduced the growth rate of xenografted OVCAR3 cells in vivo. Based on results from WGCNA and previous studies, western blot assays in cultured OC cells demonstrated that ANGPTL4 activates the Extracellular signal-related kinases 1 and 2 (ERK1/2) pathway and this results in upregulation of c-Myc, Cyclin D1, and MMP2 expression. Suggesting that the above mechanism mediates the pro-oncogenic actions of ANGPTL4T in OC, the pro-survival effects of ANGPTL4 were largely abolished upon inhibition of ERK1/2 signaling with PD98059. Conclusions Our work suggests that the hypoxia-associated gene ANGPTL4 stimulates OC progression through activation of the ERK1/2 pathway. These findings may offer a new prospect for targeted therapies for the treatment of OC.