The association between lower extremity function and cardiovascular diseases risk in older Chinese adults: Longitudinal evidence from a nationwide cohort.

BACKGROUND: Older adults in China are at a high risk of cardiovascular diseases (CVD), and impaired lower extremity function (LEF) is commonly observed in this demographic. This study aimed at assessing the association between LEF and CVD, thus providing valuable insights for clinical practice and public health policies. METHODS: A sample of 4,636 individuals was included from the China Health and Retirement Longitudinal Study (CHARLS) dataset. Logistic regression and cox proportional hazard regression model was utilized to study the association between LEF and CVD incidence. Cross-lagged panel models were utilized to investigate the potential causal association between LEF and CVD over time. RESULTS: Poor LEF was significantly associated with a higher risk of CVD in the total population [OR (95 % CI): 1.62 (1.27-2.05), P < 0.001]. Individuals with poor LEF demonstrated an increased risk of developing CVD [HR (95 % CI): 1.11 (1.02-1.23), P < 0.05], particularly stroke, compared to those with good LEF. And those with poor LEF had higher risks for heart disease [1.21 (1.00-1.45), P < 0.05] and stroke [1.98 (1.47-2.67), P < 0.001]. CONCLUSION: The results suggest the potential usefulness of the Short Physical Performance Battery (SPPB) for classifying stroke risk in older Chinese adults, which also suggested that preventing and/or improving LEF may be beneficial for reducing stroke incidence and promoting healthy aging for older adults.

Analysis on the location of scalp acupuncture lines based on the 2021 version of Standardized Manipulations of Acupuncture and Moxibustion--Part 2： Scalp Acupuncture. / 2021版《针灸技术操作规范（第2部分）：头针》头穴线定位疑析.

In order to better promote the popularization and application of the national standard of Standardized Manipulations of Acupuncture and Moxibustion--Part 2： Scalp Acupuncture (GB/T 21709.2-2021), and to provide reference for the improvement and formulation of the next version, in the present paper, the differences about the position descriptions of two scalp acupuncture lines Dingnie Qianxiexian (anterior oblique line of vertex-temporal, MS6) and Dingpangxian 1 (lateral line 1 of vertex, MS8) between the new (GB/T 21709.2-2021) and old (GB/T 21709.2-2008) versions of the national standards as well as the International Standard Proposal of Scalp Acupuncture Point were compared, and the disputes still existing in the 2021 version were discussed. Although the 2021 version has made relevant amendments in some controversial or non-standard contents in the 2008 version, there are still some inappropriate contents. Firstly, only the relevant revision in the attached figure 3 was mentioned in the preface, without mention of the word revision about MS6 in both English and Chinese, but actually "Chengguang" (BL6) has been changed to "Tongtian" (BL7). Secondly, The attached figure does not match the word description. There is a revision in the attached figure and text at the same time, in which the text description of Qianding (GV21) of the MS6 has not been revised, but the front Shencong (EX-HN1) in the attached figure has been changed to GV21, which is obviously inconsistent with the positioning of the MS6 according to the WHO international standard, and the basis for the revision is not known. These revisions of the 2021 version of national standard on the position of the two scalp acupoint lines in the 2008 version are inconsistent, which may make many colleagues in the acupuncture field confused. Thus, further revision is necessary.

Sub-Nanogram Resolution Measurement of Inertial Mass and Density Using Magnetic-Field-Guided Bubble Microthruster.

Artificial micro/nanomotors using active particles hold vast potential in applications such as drug delivery and microfabrication. However, upgrading them to micro/nanorobots capable of performing precise tasks with sophisticated functions remains challenging. Bubble microthruster (BMT) is introduced, a variation of the bubble-driven microrobot, which focuses the energy from a collapsing microbubble to create an inertial impact on nearby target microparticles. Utilizing ultra-high-speed imaging, the microparticle mass and density is determined with sub-nanogram resolution based on the relaxation time characterizing the microparticle's transient response. Master curves of the BMT method are shown to be dependent on the viscosity of the solution. The BMT, controlled by a gamepad with magnetic-field guidance, precisely manipulates target microparticles, including bioparticles. Validation involves measuring the polystyrene microparticle mass and hollow glass microsphere density, and assessing the mouse embryo mass densities. The BMT technique presents a promising chip-free, real-time, highly maneuverable strategy that integrates bubble microrobot-based manipulation with precise bioparticle mass and density detection, which can facilitate microscale bioparticle characterizations such as embryo growth monitoring.

Revisiting the advances and challenges in the clinical applications of extracellular vesicles in cancer.

Extracellular vesicles (EVs) have been the subject of an exponentially growing number of studies covering their biogenesis mechanisms, isolation and analysis techniques, physiological and pathological roles, and clinical applications, such as biomarker and therapeutic uses. Nevertheless, the heterogeneity of EVs both challenges our understanding of them and presents new opportunities for their potential application. Recently, the EV field experienced a wide range of advances. However, the challenges also remain huge. This review focuses on the recent progress and difficulties encountered in the practical use of EVs in clinical settings. In addition, we also explored the concept of EV heterogeneity to acquire a more thorough understanding of EVs and their involvement in cancer, specifically focusing on the fundamental nature of EVs.

Precipitation variation: a key factor regulating plant diversity in semi-arid livestock grazing lands.

Livestock presence impacts plant biodiversity (species richness) in grassland ecosystems, yet extent and direction of grazing impacts on biodiversity vary greatly across inter-annual periods. In this study, an 8-year (2014-2021) grazing gradient experiment with sheep was conducted in a semi-arid grassland to investigate the impact of grazing under different precipitation variability on biodiversity. The results suggest no direct impact of grazing on species richness in semi-arid Stipa grassland. However, increased grazing indirectly enhanced species richness by elevating community dominance (increasing the sheltering effect of Stipa grass). Importantly, intensified grazing also regulates excessive community biomass resulting from increased inter-annual wetness (SPEI), amplifying the positive influence of annual humidity index on species richness. Lastly, we emphasize that, in water-constrained grassland ecosystems, intra-annual precipitation variability (PCI) was the most crucial factor driving species richness. Therefore, the water-heat synchrony during the growing season may alleviate physiological constraints on plants, significantly enhancing species richness as a result of multifactorial interactions. Our study provides strong evidence for how to regulate grazing intensity to increase biodiversity under future variable climate patterns. We suggest adapting grazing intensity according to local climate variability to achieve grassland biodiversity conservation.

IGFBP1a is a nutrient deficient response factor that can inhibit fish reproduction through the hypothalamus-pituitary-ovary axis†.

Reproduction is a high energy consuming process, so long-term malnutrition can significantly inhibit gonadal development. However, little is known about the molecular mechanism by which fasting inhibits reproduction. Our present study found that fasting could dramatically induce insulin-like growth factor binding protein 1 (IGFBP1) expression in the liver, hypothalamus, pituitary and ovaries of grass carp. In addition, IGFBP1a in the hypothalamus-pituitary-gonad axis could inhibit the development of gonads. These results indicated that fasting may participate in the regulation of fish gonadal development through the mediation of IGFBP1a. Further studies found that IGFBP1a could markedly inhibit gonadotropin-releasing hormone 3 expressions in hypothalamus cells. At the pituitary level, IGFBP1a could significantly reduce the gonadotropin hormones (LH and FSH) expression by blocking the action of pituitary insulin-like growth factor 1. Interestingly, IGFBP1a could also directly inhibit the expression of lhr, fshr, and sex steroid hormone synthase genes (cyp11a, cyp17a, and cyp19a1) in the ovary. These results indicated that IGFBP1a should be a nutrient deficient response factor that could inhibit fish reproduction through the hypothalamus-pituitary-ovary axis.

Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.

After undergoing metabolic reprogramming, tumor cells consume additional glutamine to produce amino acids, nucleotides, fatty acids, and other substances to facilitate their unlimited proliferation. As such, the metabolism of glutamine is intricately linked to the survival and progression of cancer cells. Consequently, targeting the glutamine metabolism presents a promising strategy to inhibit growth of tumor cell and cancer development. This review describes glutamine uptake, metabolism, and transport in tumor cells and its pivotal role in biosynthesis of amino acids, fatty acids, nucleotides, and more. Furthermore, we have also summarized the impact of oncogenes like C-MYC, KRAS, HIF, and p53 on the regulation of glutamine metabolism and the mechanisms through which glutamine triggers mTORC1 activation. In addition, role of different anti-cancer agents in targeting glutamine metabolism has been described and their prospective applications are assessed.

ACnerf: enhancement of neural radiance field by alignment and correction of pose to reconstruct new views from a single x-ray.

Objective.Computed tomography (CT) is widely used in medical research and clinical diagnosis. However, acquiring CT data requires patients to be exposed to considerable ionizing radiance, leading to physical harm. Recent studies have considered using neural radiance field (NERF) techniques to infer the full-view CT projections from single-view x-ray projection, thus aiding physician judgment and reducing Radiance hazards. This paper enhances this technique in two directions: (1) accurate generalization capabilities for control models. (2) Consider different ranges of viewpoints.Approach.Building upon generative radiance fields (GRAF), we propose a method called ACnerf to enhance the generalization of the NERF through alignment and pose correction. ACnerf aligns with a reference single x-ray by utilizing a combination of positional encoding with Gaussian random noise (latent code) obtained from GRAF training. This approach avoids compromising the 3D structure caused by altering the generator. During inference, a pose judgment network is employed to correct the pose and optimize the rendered viewpoint. Additionally, when generating a narrow range of views, ACnerf employs frequency-domain regularization to fine-tune the generator and achieve precise projections.Main results.The proposed ACnerf method surpasses the state-of-the-art NERF technique in terms of rendering quality for knee and chest data with varying contrasts. It achieved an average improvement of 2.496 dB in PSNR and 41% in LPIPS for 0°-360° projections. Additionally, for -15° to 15° projections, ACnerf achieved an average improvement of 0.691 dB in PSNR and 25.8% in LPIPS.Significance.With adjustments in alignment, inference, and rendering range, our experiments and evaluations on knee and chest data of different contrasts show that ACnerf effectively reduces artifacts and aberrations in the new view. ACnerf's ability to recover more accurate 3D structures from single x-rays has excellent potential for reducing damage from ionising radiation in clinical diagnostics.

Solution-processed bilayer InGaZnO/In2O3thin film transistors at low temperature by lightwave annealing.

At low temperatures about 230 °C, bilayer InGaZnO/In2O3thin film transistors (TFTs) were prepared by a solution process with lightwave annealing. The InGaZnO/In2O3bilayer TFTs with SiO2as dielectric layer show high electrical performances, such as a mobility of 7.63 cm2V-1s-1, a threshold voltage (Vth) of 3.8 V, and an on/off ratio higher than 107, which are superior to single-layer InGaZnO TFTs or In2O3TFTs. Moreover, bilayer InGaZnO/In2O3TFTs demonstrated a great bias stability enhancement due to the introduction of top InGaZnO film act as a passivation layer, which could prevent the interaction of ambient air with the bottom In2O3layer. By using high dielectric constant AlOxfilm, the InGaZnO/In2O3TFTs exhibit an improved mobility of 47.7 cm2V-1s-1. The excellent electrical performance of the solution-based InGaZnO/In2O3TFTs shows great application potential for low-cost flexible printed electronics.

Molecular mechanism of Xiaohuoluo wan for rheumatoid arthritis by integrating in vitro and in vivo chemomics and network pharmacology.

The cause of rheumatoid arthritis (RA) is unclear. Xiaohuoluo wan (XHLW) is a classical Chinese medicine that is particularly effective in the treatment of RA. Given the chemical composition of XHLW at the overall level has been little studied and the molecular mechanism for the treatment of RA is not clear, we searched for the potential active compounds of XHLW and explored their anti-inflammatory mechanism in the treatment of RA by flexibly integrating the high-resolution ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based in vitro and in vivo chemomics, network pharmacology, and other means. The results of the study identified that the active compounds of XHLW, such as alkaloids, nucleosides, and fatty acids, may play an anti-inflammatory role by regulating key targets such as IL-2, STAT1, JAK3, and MAPK8, inducing immune response through IL-17 signaling pathway, T-cell receptor, FoxO, tumor necrosis factor (TNF), and so forth, inhibiting the release of inflammatory factors and resisting oxidative stress and other pathways to treat RA. The results of this study provide referable data for the screening of active compounds and the exploration of molecular mechanisms of XHLW in the treatment of RA.

MYCT1 attenuates renal fibrosis and tubular injury in diabetic kidney disease.

Tubulointerstitial abnormalities contribute to the progression of diabetic kidney disease (DKD). However, the underlying mechanism of the pathobiology of tubulointerstitial disease is largely unknown. Here, we showed that MYCT1 expression was downregulated in in vitro and in vivo DKD models. Adeno-associated virus (AAV)-Myct1 significantly attenuated renal dysfunction and tubulointerstitial fibrosis in diabetic db/db mice and downregulated Sp1 transcription and TGF-ß1/SMAD3 pathway activation. In human proximal tubular epithelial cells, high glucose-induced high expression of SP1 and TGF-ß1/SMAD3 pathway activation as well as overaccumulation of extracellular matrix (ECM) were abrogated by MYCT1 overexpression. Mechanistically, the binding of VDR to the MYCT1 promoter was predicted and confirmed using dual-luciferase reporter and ChIP analysis. VDR transcriptionally upregulates MYCT1. Our data reveal MYCT1 as a new and potential therapeutic target in treating DKD.

Extracellular vesicle-cell adhesion molecules in tumours: biofunctions and clinical applications.

Cell adhesion molecule (CAM) is an umbrella term for several families of molecules, including the cadherin family, integrin family, selectin family, immunoglobulin superfamily, and some currently unclassified adhesion molecules. Extracellular vesicles (EVs) are important information mediators in cell-to-cell communication. Recent evidence has confirmed that CAMs transported by EVs interact with recipient cells to influence EV distribution in vivo and regulate multiple cellular processes. This review focuses on the loading of CAMs onto EVs, the roles of CAMs in regulating EV distribution, and the known and possible mechanisms of these actions. Moreover, herein, we summarize the impacts of CAMs transported by EVs to the tumour microenvironment (TME) on the malignant behaviour of tumour cells (proliferation, metastasis, immune escape, and so on). In addition, from the standpoint of clinical applications, the significance and challenges of using of EV-CAMs in the diagnosis and therapy of tumours are discussed. Finally, considering recent advances in the understanding of EV-CAMs, we outline significant challenges in this field that require urgent attention to advance research and promote the clinical applications of EV-CAMs. Video Abstract.

Enhanced removal of cis-1,2-dichloroethene and vinyl chloride in groundwater using ball-milled sulfur- and biochar-modified zero-valent iron: From the laboratory to the field.

Sulfidated zero-valent iron (ZVI) and biochar-supported ZVI have received increasing attention for their potential to dechlorinate trichloroethylene. However, minimal data are available regarding the combined effect of sulfur and biochar ZVI on trichloroethylene byproducts. The primary aim of the current study is to determine whether sulfur- and biochar-modified ZVI (ZVI-BC-S) enhances the removal of cis-1,2-dichloroethene (cDCE) and vinyl chloride (VC) from groundwater. Results show that biochar and sulfur facilitated the milling of ZVI-BC-S into micro- and nanoscale particles and increased FeS formation. Moreover, the rates of cDCE and VC removal by ZVI-S increased by 30.1% and 30.2%, respectively, compared to those obtained with ZVI, owing to enhanced dechlorination via ß-elimination by sulfur. Meanwhile, treatment with ZVI-BC-S harnessed the benefits of biochar and sulfur to enhance the cDCE and VC removal rates by 62.0% and 67.7%, respectively. Mechanistically, biochar enhanced the corrosion of ZVI-S to increase FeS production and enhance the electron transfer, ß-elimination, and hydrogenolysis involved in cDCE and VC dechlorination. The effectiveness of ZVI-BC-S was confirmed in a field demonstration, during which cDCE and VC concentrations significantly decreased within 10 days following injection. The findings of this study can help inform the rational design of ZVI for in-situ remediation of chlorinated hydrocarbons in groundwater.

Crossover behavior in stress relaxations of poroelastic and viscoelastic dominant hydrogels.

The mechanical response and relaxation behavior of hydrogels are crucial to their diverse functions and applications. However, understanding how stress relaxation depends on the material properties of hydrogels and accurately modeling relaxation behavior at multiple time scales remains a challenge for soft matter mechanics and soft material design. While a crossover phenomenon in stress relaxation has been observed in hydrogels, living cells, and tissues, little is known about how the crossover behavior and characteristic crossover time depend on material properties. In this study, we conducted systematic atomic-force-microscopy (AFM) measurements of stress relaxation in agarose hydrogels with varying types, indentation depths, and concentrations. Our findings show that the stress relaxation of these hydrogels features a crossover from short-time poroelastic relaxation to long-time power-law viscoelastic relaxation at the micron scale. The crossover time for a poroelastic-dominant hydrogel is determined by the length scale of the contact and diffusion coefficient of the solvent inside the gel network. In contrast, for a viscoelastic-dominant hydrogel, the crossover time is closely related to the shortest relaxation time of the disordered network. We also compared the stress relaxation and crossover behavior of hydrogels with those of living cells and tissues. Our experimental results provide insights into the dependence of crossover time on poroelastic and viscoelastic properties and demonstrate that hydrogels can serve as model systems for studying a wide range of mechanical behaviors and emergent properties in biomaterials, living cells, and tissues.

Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications.

Cancer stem cells(CSCs) play a key role in regulating tumorigenesis, progression, as well as recurrence, and possess typical metabolic characteristics. Autophagy is a catabolic process that can aid cells to survive under stressful conditions such as nutrient deficiency and hypoxia. Although the role of autophagy in cancer cells has been extensively studied, CSCs possess unique stemness, and their potential relationship with autophagy has not been fully analyzed. This study summarizes the possible role of autophagy in the renewal, proliferation, differentiation, survival, metastasis, invasion, and treatment resistance of CSCs. It has been found that autophagy can contribute to the maintenance of CSC stemness, facilitate the tumor cells adapt to changes in the microenvironment, and promote tumor survival, whereas in some other cases autophagy acts as an important process involved in the deprivation of CSC stemness thus leading to tumor death. Mitophagy, which has emerged as another popular research area in recent years, has a great scope when explored together with stem cells. In this study, we have aimed to elaborate on the mechanism of action of autophagy in regulating the functions of CSCs to provide deeper insights for future cancer treatment.

Unveiling the role of biochar in simultaneous removal of hexavalent chromium and trichloroethylene by biochar supported nanoscale zero-valent iron.

The simultaneous removal of hexavalent chromium (Cr(VI)) and Trichloroethylene (TCE) is facing great challenges, and the influences of the biochar on their removal by nanoscale zero-valent iron (nZVI) are poorly understood and seldom addressed in the literature. The rice straw pyrolysis at 700 °C (RS700) and their supported nZVI composites were investigated on the removal of Cr(VI) and TCE by batch experiments. The surface area and chromium bonding state of biochar supported nZVI with and without Cr(VI)-TCE loading were analyzed by Brunauer-Emmett-Teller analysis and X-ray photoelectron spectroscopy. In single pollutants system, the highest removal amounts of Cr(VI) and TCE were observed in RS700-HF-nZVI (76.36 mg/g) and RS700-HF (32.32 mg/g), respectively. The Cr(VI) removal was attributed to the reduction by Fe(II) with the adsorption by biochar primarily controlling the TCE removal. The mutual inhibition was revealed in simultaneous removal of Cr(VI) and TCE, in which the reduction of Cr(VI) was decreased due to the adsorption of Fe(II) by biochar, while the TCE adsorption was primarily inhibited owing to the blockage of surface pores of biochar supported nZVI by chromium­iron oxides. Therefore, biochar supported nZVI could be potentially used for the combined contaminated groundwater remediation, but the mutual inhibition should be evaluated.

Enhancement of the immune response via the facilitation of dendritic cell maturation by CD-205 Receptor-mediated Long-circling liposomes acting as an antigen and astragalus polysaccharide delivery system.

CD-205 receptor-mediated dendritic cell (DC) targeting liposomes are commonly used as a delivery system for inducing a strong T-cell immune response or specific immune tolerance. This delivery system can carry both the antigen and adjuvant, thereby modulating DC maturation and also activating the T-cell response. In order to maximize the desired therapeutic effects of Astragalus polysaccharides (APS) and induce an efficient cellular and humoral immune response against the antigen, ovalbumin (OVA) and APS were encapsulated in long-circling liposomes conjugated with anti-CD-205 receptor antibodies to produce CD-205-targeted liposomes (iLPSM). We explored using a series of experiments evaluating the targeting efficiency of iLPSM. In vitro, iLPSM nanoparticles promoted the proliferation of macrophages, and the nanoparticles were rapidly phagocytized by macrophages. In vivo, iLPSM significantly improved the antibody titers of OVA-specific IgG and IgG, isotypes cytokine production, and T and B lymphocyte differentiation. Furthermore, iLPSM facilitated the maturation of DCs. In addition, iLPSM nanoparticles could prolong the retention time of nanoparticles at the injection site, leading to a strong, sustained immune response. These results show that the CD-205 antibody successfully binds to the corresponding cell receptor.

Impact of digital infrastructure inputs on industrial carbon emission intensity: evidence from China's manufacturing panel data.

Digital infrastructure inputs (DIIs) are vital in strengthening the framework for developing the digital economy and encouraging economic growth. Nonetheless, the risks of environmental contamination are pervasively caused by the rapid expansion and utilization of digital infrastructure. Assessing the carbon emission intensity (CEI) and level of the DIIs of 18 manufacturing in China as the research subject, this study discusses the heterogeneous behavior of various input sources and industries. Furthermore, a two-way fixed effects model, threshold effects model, mediating effects model and moderated mediation effects model have been adopted to examine the nexus between DIIs and CEI of manufacturing. The results show that (1) DIIs raise China's manufacturing CEI and exert a non-linear threshold effect. (2) From the perspective of national attributes, the foreign DIIs will put more pressure on reducing the CEI in China. From the perspective of industry characteristics, DIIs are the most unfavorable for low-carbon development in capital-intensive industries. (3) Due to the mediating effect of total factor productivity (TFP), the positive influence of DIIs on CEI has dramatically diminished. (4) Participation in the global value chain (PAR) and foreign direct investment (FDI) exert moderating effects in the process of the direct effect and mediating effects. In light of the aforementioned conclusions, specific recommendations for developing digital infrastructure and reducing carbon emissions are proposed.

Machine Learning to Dynamically Predict In-Hospital Venous Thromboembolism After Inguinal Hernia Surgery: Results From the CHAT-1 Study.

BACKGROUND: The accuracy of current prediction tools for venous thromboembolism (VTE) events following hernia surgery remains insufficient for individualized patient management strategies. To address this issue, we have developed a machine learning (ML)-based model to dynamically predict in-hospital VTE in Chinese patients after hernia surgery. METHODS: ML models for the prediction of postoperative VTE were trained on a cohort of 11 305 adult patients with hernia from the CHAT-1 trial, which included patients across 58 institutions in China. In data processing, data imputation was conducted using random forest (RF) algorithm, and balanced sampling was done by adaptive synthetic sampling algorithm. Data were split into a training cohort (80%) and internal validation cohort (20%) prior to oversampling. Clinical features available pre-operatively and postoperatively were separately selected using the Sequence Forward Selection algorithm. Nine-candidate ML models were applied to the pre-operative and combined datasets, and their performance was evaluated using various metrics, including area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using importance scores, which were calculated by transforming model features into scaled variables and representing them in radar plots. RESULTS: The modeling cohort included 2856 patients, divided into 2536 cases for derivation and 320 cases for validation. Eleven pre-operative variables and 15 combined variables were explored as predictors related to in-hospital VTE. Acceptable-performing models for pre-operative data had an AUROC ≥ 0.60, including logistic regression, support vector machine with linear kernel (SVM_Linear), attentive interpretable Tabular learning (TabNet), and RF. For combined data, logistic regression, SVM_Linear, and TabNet had better performance, with an AUROC ≥ 0.65 for each model. Based on these models, 7 pre-operative predictors and 10 combined predictors were depicted in radar plots. CONCLUSIONS: A ML-based approach for the identification of in-hospital VTE events after hernia surgery is feasible. TabNet showed acceptable performance, and might be useful to guide clinical decision making and VTE prevention. Further validated study will strengthen this finding.

Mapping rabies distribution in China: a geospatial analysis of national surveillance data.

OBJECTIVES: Dog-mediated human rabies remains an important public health problem in China. In this study, we aimed to understand the spatiotemporal variation of rabies and examine its nonmedical ecological factors. METHODS: In this study, we used the annual incidence data for rabies at the province level in China to describe the incidence trends for the period 2004-2019 and used a Bayesian hierarchical spatiotemporal model to determine the impacts of environmental, economic, and demographic factors. RESULTS: From 2004 to 2019, there were 26,593 cases reported in 31 provinces in Mainland China, and the annual incidence increased from 0.02 per 100,000 in 2004 to 0.14 in 2007, substantially decreased in 2008, and was gradually declining thereafter. Guizhou, Guangxi, Hunan, and Hainan were four high-risk provinces, and Yunnan and Anhui provinces showed an increased risk in 2018 and 2019. Temperature and per capita gross domestic product were significantly positively correlated with the disease risk. The standardized morbidity ratio of rabies is likely to increase by 28% (relative risk: 1.28, 95% credible interval: 1.13-1.36) for every 1°C rise in temperature, and 17% (relative risk: 1.17, 95% credible interval: 1.01-1.34) for every 10,000 yuan increase in per capita gross domestic product. CONCLUSION: In most provinces in China, the risk of rabies has been reduced to a persistently low level. However, the progress of rabies control in six provinces have been less than satisfactory. The study highlights interventions, such as enhancing animal vaccination need to be implemented in these priority areas.