Corrigendum: Characterizing the neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

[This corrects the article DOI: 10.3389/fcell.2021.793073.].

ZNF468-mediated epigenetic upregulation of VEGF-C facilitates lymphangiogenesis and lymphatic metastasis in ESCC via PI3K/Akt and ERK1/2 signaling pathways.

PURPOSE: Dysfunctional lymphangiogenesis is pivotal for various pathological processes including tumor lymph node metastasis which is a crucial cause of therapeutic failure for ESCC. In this study, we aim to elucidate the molecular mechanisms and clinical relevance of Zinc-finger protein ZNF468 in lymphangiogenesis and lymphatic metastasis in ESCC. METHODS: Immunohistochemistry, Western blot, Kaplan-Meier plotter analysis and Gene Set Enrichment Analysis were preformed to detect the association of ZNF468 with lymphangiogenesis and poor prognosis in ESCC patients. Foot-pads lymph node metastasis model, tube formation assay, 3D-culture assay and invasion assay were preformed to verify the effect of ZNF468 on lymphangiogenesis and lymph node metastasis. CUT&Tag analysis, immunoprecipitation and mass spectrometry analysis and ChIP-PCR assay were preformed to study the molecular mechanisms of ZNF468 in lymphangiogenesis. RESULTS: We found that ectopic expression of ZNF468 was correlated with higher microlymphatic vessel density in ESCC tissues, leading to poorer prognosis of ESCC patients. ZNF468 enhanced the capacity of lymphangiogenesis and promoted lymphatic metastasis in ESCC both in vitro and in vivo. However, silencing ZNF468 reversed these phenotypes in ESCC. Mechanically, we demonstrated that ZNF468 recruits the histone modification factors (PRMT1/HAT1) to increase the levels of H4R2me2a and H3K9ac, which then leads to the recruitment of the transcription initiation complex on the VEGF-C promoter, ultimately promoting the upregulation of VEGF-C transcription. Strikingly, the promoting effect of lymphatic metastasis induced by ZNF468 in ESCC was abrogated by targeting PRMT1 using Arginine methyltransferase inhibitor-1 or silencing VEGF-C. Furthermore, we found that the activation of PI3K/AKT and ERK1/2 signaling is required for ZNF468-medicated lymphatic metastasis in ESCC. Importantly, the clinical relevance between ZNF468 and VEGF-C were confirmed not only in ESCC samples and but also in multiple cancer types. CONCLUSION: Our results identified a precise mechanism underlying ZNF468-induced epigenetic upregulation of VEGF-C in facilitating lymphangiogenesis and lymph node metastasis of ESCC, which might provide a novel prognostic biomarker and potential therapeutic for ESCC patients.

Image/Video Coding and Processing Techniques for Intelligent Sensor Nodes.

There is an increasing interest in developing intelligent sensor nodes which enable intelligent processing for Internet of Things (IoT) surveillance, remote sensing, and smart city applications [...].

Ingenious Structure Engineering to Enhance Piezoelectricity in Poly(vinylidene fluoride) for Biomedical Applications.

The future development of wearable/implantable sensing and medical devices relies on substrates with excellent flexibility, stability, biocompatibility, and self-powered capabilities. Enhancing the energy efficiency and convenience is crucial, and converting external mechanical energy into electrical energy is a promising strategy for long-term advancement. Poly(vinylidene fluoride) (PVDF), known for its piezoelectricity, is an outstanding representative of an electroactive polymer. Ingeniously designed PVDF-based polymers have been fabricated as piezoelectric devices for various applications. Notably, the piezoelectric performance of PVDF-based platforms is determined by their structural characteristics at different scales. This Review highlights how researchers can strategically engineer structures on microscopic, mesoscopic, and macroscopic scales. We discuss advanced research on PVDF-based piezoelectric platforms with diverse structural designs in biomedical sensing, disease diagnosis, and treatment. Ultimately, we try to give perspectives for future development trends of PVDF-based piezoelectric platforms in biomedicine, providing valuable insights for further research.

Persistent glucose consumption under antibiotic treatment protects bacterial community.

Antibiotics typically induce major physiological changes in bacteria. However, their effect on nutrient consumption remains unclear. Here we found that Escherichia coli communities can sustain normal levels of glucose consumption under a broad range of antibiotics. The community-living resulted in a low membrane potential in the bacteria, allowing slow antibiotic accumulation on treatment and better adaptation. Through multi-omics analysis, we identified a prevalent adaptive response characterized by the upregulation of lipid synthesis, which substantially contributes to sustained glucose consumption. The consumption was maintained by the periphery region of the community, thereby restricting glucose penetration into the community interior. The resulting spatial heterogeneity in glucose availability protected the interior from antibiotic accumulation in a membrane potential-dependent manner, ensuring rapid recovery of the community postantibiotic treatment. Our findings unveiled a community-level antibiotic response through spatial regulation of metabolism and suggested new strategies for antibiotic therapies.

Infection and biogeographical characteristics of Paragonimus westermani and P. skrjabini in humans and animal hosts in China: A systematic review and meta-analysis.

BACKGROUND: Paragonimiasis, primarily caused by Paragonimus westermani and P. skrjabini in China, is a common food-borne parasitic zoonosis. However, the national distribution of Paragonimus spp. infection and its associated environmental determinants remain poorly understood. In this paper, we summarize the infection of P. westermani and P. skrjabini and describe key biogeographical characteristics of the endemic areas in China. METHODS: Data on Paragonimus infection in humans and animal hosts were extracted from eight electronic databases, including CNKI, CWFD, Chongqing VIP, SinoMed, Medline, Embase, PubMed, and Web of Science. A random-effects meta-analysis model was used to estimate the pooled prevalence. All survey locations were georeferenced and plotted on China map, and scatter plots were used to illustrate the biogeographical characteristics of regions reporting Paragonimus infection. RESULTS: A total of 28,948 cases of human paragonimiasis have been documented, with 2,401 cases reported after 2010. Among the 11,443 cases with reported ages, 88.05% were children or adolescents. The pooled prevalence of P. skrjabini is 0.45% (95% CI: 0.27-0.66%) in snails, 31.10% (95% CI: 24.77-37.80%) in the second intermediate host, and 20.31% (95% CI: 9.69-33.38%) in animal reservoirs. For P. westermani, the pooled prevalence is 0.06% (95% CI: 0.01-0.13%) in snails, 52.07% (95% CI: 43.56-60.52%) in the second intermediate host, and 21.40% (95% CI: 7.82-38.99%) in animal reservoirs. Paragonimus are primarily distributed in regions with low altitude, high temperature, and high precipitation. In northeastern China, only P. westermani infections have been documented, while in more southern areas, infections of both P. westermani and P. skrjabini have been reported. CONCLUSIONS: Paragonimiasis remains prevalent in China, particularly among children and adolescents. Variations exist in the intermediate hosts and geographical distribution of P. westermani and P. skrjabini. Additionally, altitude, temperature, and precipitation may influence the distribution of Paragonimus.

Bu-Shen-Ning-Xin decoction ameliorates premature ovarian insufficiency by suppressing oxidative stress through rno_circRNA_012284/rno_miR-760-3p/HBEGF pathway.

BACKGROUND: POI (premature ovarian insufficiency) refers to premature and rapid decline of ovarian reserve function in women before the age of 40, which can be manifested as menstrual disorders, endocrine abnormalities and low fertility. Bu-Shen-Ning-Xin decoction (BSNXD) has been found to have therapeutic effects on POI. Nevertheless, how it exerts therapeutic effects remains elusive. PURPOSE: This research aims to clarify the pharmacological mechanisms of BSNXD. METHODS: We applied Ultra Performance Liquid Chromatography (UPLC) to identify the main components of BSNXD.4-vinylcyclohexene diepoxide(VCD)was used to induce POI models. ELISA detected the serum level of hormones. H&E staining evaluated the morphology of ovarian tissues.CircRNA and mRNA expression profiles in the ovaries of both POI rats and those treated with BSNXD were detected. Then, dysregulated circRNAs and mRNAs that were potentially altered by BSNXD were screened. Network pharmacology analysis was performed to identify drug targets of BSNXD active ingredients. A circRNA-miRNA-mRNA network and an oxidative stress(OS)-related subnetwork were constructed. Expression of rno_circRNA_012284, rno_miR-760-3p, and HBEGF(Heparin-binding epidermal growth factor-like growth factor) was measured by RT-PCR and their binding were verified by dual-luciferase reporter assays. ROS was measured through DCFH-DA fluorescence probes. The HBEGF target was selected for molecular docking with key active ingredients.Surface plasmon resonance(SPR) was applied to verify the binding ability and affinity between components and HBEGF. RESULTS: UPLC analysis indicated that 6 chemical compounds including berberine, paeoniflorin, morroniside,gallic acid, loganin, baicalin were identified.Elevated FSH and LH levels, suppressed E2 and AMH levels in the serum, and inhibited follicles and corpus luteums in the ovarian tissues of VCD-induced rats were notably reversed by BSNXD.In total, 992 up- and 1135 down-regulated circRNAs, and 205 up- and 243 down-regulated mRNAs were found in POI rat ovaries following BSNXD administration. Furthermore, 198 drug targets of BSNXD were identified. An OS-related and BSNXD-targeted ceRNA subnetwork composed of rno_circRNA_012284/rno_miR-760-3p/HBEGF was established. rno_circRNA_012284 and HBEGF were up-regulated and rno_miR-760-3p was down-regulated in POI ovarian granulosa cells (OGCs) after BSNXD administration. rno_circRNA_012284 was a sponge of rno_miR-760-3p to elevate HBEGF expression. Moreover, rno_circRNA_012284 overexpression alleviated POI-induced excessive ROS generation in ovarian granulosa cells, while rno_circRNA_012284 inhibition exerted the opposite effect. Finally,molecular docking speculated active ingredients of each herb acted on HBEGF to reduce the OS. SPR tests showed that Berberine,Baicalein,Quercetin,Pachymic acid,Paeoniflorin exhibited satisfying affinity with HBEGF protein. CONCLUSION: This study demonstrates that BSNXD ameliorates POI partly by attenuating OS in ovarian granulosa cells via rno_circRNA_012284/rno_miR-760-3p/HBEGF axis, uncovering the pharmacological mechanisms of BSNXD in alleviating POI.

Macrocyclic-based strategy in drug design: From lab to the clinic.

Macrocyclic compounds have emerged as potent tools in the field of drug design, offering unique advantages for enhancing molecular recognition, improving pharmacokinetic properties, and expanding the chemical space accessible to medicinal chemists. This review delves into the evolutionary trajectory of macrocyclic-based strategies, tracing their journey from laboratory innovations to clinical applications. Beginning with an exploration of the defining structural features of macrocycles and their impact on drug-like characteristics, this discussion progresses to highlight key design principles that have facilitated the development of diverse macrocyclic drug candidates. Through a series of illustrative representative case studies from approved macrocyclic drugs and candidates spanning various therapeutic areas, particular emphasis is placed on their efficacy in targeting challenging protein-protein interactions, enzymes, and receptors. Additionally, this review thoroughly examines how macrocycles effectively address critical issues such as metabolic stability, oral bioavailability and selectivity. Valuable insights into optimization strategies employed during both approved and clinical phases underscore successful translation of promising leads into efficacious therapies while providing valuable perspectives on harnessing the full potential of macrocycles in drug discovery and development endeavors.

Polyphenol-mediated hyaluronic acid/tannic acid hydrogel with short gelation time and high adhesion strength for accelerating wound healing.

Wound healing is a complex process involving a complicated interplay between numerous cell types and vascular systems. Hyaluronic acid (HA)-based hydrogel facilitates wound healing, and is involved in all processes. However, slow gelation speed and weak adhesion strength limit its ability to form a stable physical barrier quickly. Herein, we propose a HA-based composite hydrogel as the wound dressing based on oxidative coupling reaction. Tannic acid and dopamine-coated carbon particles (DCPs) containing abundant phenolic hydroxyl groups are incorporated into the HA-based hydrogel for increasing the number of crosslinking sites of oxidative coupling of the hydrogel and enhancing adhesion through the formation of covalent bonds and hydrogen bonds between hydrogel and wound sites. The composite hydrogel exhibits short gelation time (<6 s) and high adhesion strength (>8.1 kPa), which are superior to the references and commercial products of its kind. The in vitro experiments demonstrate that the hydrogel has low hemolytic reaction, negligible cytotoxicity, and the ability to promote fibroblast proliferation and migration. The in vivo full-thickness skin defect model experiments demonstrate that the hydrogel can accelerate wound healing under mild photothermal stimulation of DCPs by reducing inflammation, relieving tissue hypoxia, and promoting angiogenesis and epithelialization.

Trend of albumin nanoparticles in oncology: a bibliometric analysis of research progress and prospects.

Background: Delivery systems based on albumin nanoparticles (NPs) have recently garnered substantial interest in anti-tumor drug development. However, systematic bibliometric analyses in this field remain lacking. This study aimed to analyze the current research status, hotspots, and frontiers in the application of albumin NPs in the field of oncology from a bibliometric perspective. Methods: Using the Web of Science Core Collection (WOSCC) as the data source, retrieved articles were analyzed using software, such as VOSviewer 1.6.18 and CiteSpace 6.1.6, and the relevant visualization maps were plotted. Results: From 1 January 2000, to 15 April 2024, 2,262 institutions from 67 countries/regions published 1,624 articles related to the application of albumin NPs in the field of oncology. The USA was a leader in this field and held a formidable academic reputation. The most productive institution was the Chinese Academy of Sciences. The most productive author was Youn YS, whereas Kratz F was the most frequently co-cited author. The most productive journal was the International Journal of Nanomedicine, whereas the Journal of Controlled Release was the most co-cited journal. Future research hotspots and frontiers included "rapid and convenient synthesis methods predominated by self-assembly," "surface modification," "construction of multifunctional NPs for theranostics," "research on natural active ingredients mainly based on phenolic compounds," "combination therapy," and "clinical applications." Conclusion: Based on our bibliometric analysis and summary, we obtained an overview of the research on albumin NPs in the field of oncology, identified the most influential countries, institutions, authors, journals, and citations, and discussed the current research hotspots and frontiers in this field. Our study may serve as an important reference for future research in this field.

Predicting the impact of climate change and land use change on the potential distribution of two economic forest trees in Northeastern China.

Young shoots of Aralia elata and young leaves of Eleutherococcus senticosus are two major non-timber forest products in northeastern China. However, human activities and climate change have resulted in serious threats to the habitats of two trees, which greatly limits resource conservation and exploitation of economic forest trees. We used the MaxEnt model to predict the suitable habitats of the two economic trees and analyzed the dominant factors affecting their distribution. The results showed that the suitable habitat areas of A. elata and E. senticosus in the current period were 159950 km2 and 123449 km2, respectively, and the suitable habitats of both economic forest trees were located in the eastern part of the northeast region. Climate factors (Annual precipitation, Precipitation Seasonality) and land use factors are important variables influencing changes in suitable habitat for both trees. With the change of climate and land use in the future, the overall trend of suitable habitat for both economic forest trees shows a northward and then a southward migration. These results may provide assistance in developing strategies for resource conservation and sustainable use of A. elata and E. senticosus, and we suggest that stable and suitable habitats should be selected as areas for in situ conservation and breeding of the two economic forest trees.

Synergistic integration of climate change and zoonotic diseases by artificial intelligence: a holistic approach for sustainable solutions.

Artificial intelligence (AI) is a rapidly evolving field that can impel research in communicable diseases with respect to climate projections, ecological indicators and environmental impact, at the same time revealing new, previously overlooked events. A number of zoonotic and vector-borne diseases already show signs of expanding their northern geographical ranges and appropriate risk assessment and decision support are urgently needed. The deployment of AI-enabled monitoring systems tracking animal populations and environmental changes is of immense potential in the study of transmission under different climate scenarios. In addition, AI's capability to identify new treatments should not only accelerate drug and vaccine discovery but also help predicting their effectiveness, while its contribution to genetic pathogen speciation would assist the evaluation of spillover risks with regard to viral infections from animals to human. Close collaboration between AI experts, epidemiologists and other stakeholders is not only crucial for responding to challenges interconnected with a variety of variables effectively, but also necessary to warrant responsible AI use. Despite its wider successful implementation in many fields, AI should be seen as a complement to, rather than a replacement of, traditional public health measures.

Counting hours or calories? Metabolic regulatory role of time-restricted eating in adults with overweight and obesity: a systematic review and meta-analysis.

Time-restricted eating (TRE) effectively improves healthspan, including controlling obesity and improving metabolic health. To date, few meta-analyses have been conducted to explore the effects of various protocols of TRE in participants with overweight/obesity. PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched up until October 15, 2022. Randomized and non-randomized clinical trials that investigated the effect of TRE on body weight, body composition and cardiometabolic parameters in participants with overweight/obesity were included. Mean differences of changes from the baseline were used for all analyses between the two groups. Prespecified subgroup analyses based on different protocols of TRE were performed. Twenty-three studies were included in the meta-analysis with 1867 participants. TRE interventions led to significant changes in body weight. When energy restriction strategies were conducted in both the TRE and control groups, the weight-loss effect of TRE remained significant. TRE with 4 ∼ 8h feeding window, morning or late eating strategies, led to reduction in body weight and fat mass for at least 8 wk. Hence TRE is a potential and effective approach for weight loss for participants with overweight/obesity. An 8h-TRE intervention with a morning eating strategy for at least eight weeks might be the optimum TRE intervention mode.

HDAC8 Enhances the Function of HIF-2α by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC.

Drug resistance after long-term use of Tyrosine kinase inhibitors (TKIs) has become an obstacle for prolonging the survival time of patients with clear cell renal cell carcinoma (ccRCC). Here, genome-wide CRISPR-based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied. Mechanically, HDAC8 deacetylated ETS1 at the K245 site to promote the interaction between ETS1 and HIF-2α and enhance the transcriptional activity of the ETS1/HIF-2α complex. However, the antitumor effect of inhibiting HDAC8 on sensitized TKI is not very satisfactory. Subsequently, inhibition of HDAC8 increased the expression of NEK1, and up-regulated NEK1 phosphorylated ETS1 at the T241 site to promote the interaction between ETS1 and HIF-2α by impeded acetylation at ETS1-K245 site is showed. Moreover, TKI treatment increased the expression of HDAC8 by inhibiting STAT3 phosphorylation in ccRCC cells is also found. These 2 findings highlight a potential mechanism of acquired resistance to TKIs and HDAC8 inhibitors in ccRCC. Finally, HDAC8-in-PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC-targeted therapies.

tRNA Modifications and Dysregulation: Implications for Brain Diseases.

Transfer RNAs (tRNAs) are well-known for their essential function in protein synthesis. Recent research has revealed a diverse range of chemical modifications that tRNAs undergo, which are crucial for various cellular processes. These modifications are necessary for the precise and efficient translation of proteins and also play important roles in gene expression regulation and cellular stress response. This review examines the role of tRNA modifications and dysregulation in the pathophysiology of various brain diseases, including epilepsy, stroke, neurodevelopmental disorders, brain tumors, Alzheimer's disease, and Parkinson's disease. Through a comprehensive analysis of existing research, our study aims to elucidate the intricate relationship between tRNA dysregulation and brain diseases. This underscores the critical need for ongoing exploration in this field and provides valuable insights that could facilitate the development of innovative diagnostic tools and therapeutic approaches, ultimately improving outcomes for individuals grappling with complex neurological conditions.

Unveiling a new oceanic anoxic event at the Norian/Rhaetian boundary (Late Triassic).

The latest Triassic was characterised by protracted biotic extinctions concluding in the End-Triassic Extinction (~ 200 Ma) and a global carbon cycle perturbation. The onset of declining diversity is closely related to reducing conditions that spread globally from upper Sevatian (uppermost Norian) to across the Norian-Rhaetian boundary, likely triggered by unusually high volcanic activity. We correlate significant organic carbon cycle perturbations to an increase of CO2 in the ocean-atmosphere system, likely outgassed by the Angayucham igneous province, the onset of which is indicated by the initiation of a rapid decline in 87Sr/86Sr and 188Os/187Os seawater values. A possible causal mechanism involves elevated CO2 levels causing global warming and accelerating chemical weathering, which increased nutrient discharge to the oceans and greatly increased biological productivity. Higher export production and oxidation of organic matter led to a global O2 decrease in marine water across the Norian/Rhaetian boundary (NRB). Biotic consequences of dysoxia/anoxia include worldwide extinctions in some fossil groups, such as bivalves, ammonoids, conodonts, radiolarians.

Cross-Linkable Binders for Si Anodes in High-Energy-Density Lithium-Ion Batteries.

Although silicon (Si) has a high theoretical capacity, the large volume expansion during lithiation has greatly hindered its application in high-energy-density lithium-ion batteries (LIBs). Among the strategies for improving the performance of Si anode, the role of binders should not be underestimated. Here, a novel strategy for designing a cross-linkable binder for Si anode has been proposed. The binder with hydroxyl and nitrile groups can be in situ covalently cross-linked through the amide group in the batteries. The cross-linked binder (c-POAH) shows high elasticity and strong adhesion to Si particles and the current collector. Si||Li half coin cells using the c-POAH binder have excellent cycle performance and the capacity retention ratio is 67.1% after 100 cycles at 0.2 C. Scanning electronic microscopy images show that the c-POAH binder can contribute to suppressing the pulverization of the Si anode. Moreover, the investigation with X-ray photoelectronic spectrum demonstrates that the decomposition of the liquid electrolyte on Si anode has been mitigated and the c-POAH binder can promote the formation of a more stable SEI film. Our strategy of endowing the binder with good elasticity through in situ cross-linking has opened up a new route for developing binders, which will definitely promote the application of Si anodes in high-energy-density LIBs.

Online Measurement of Melt-Pool Width in Direct Laser Deposition Process Based on Binocular Vision and Perspective Transformation.

Direct laser deposition (DLD) requires high-energy input and causes poor stability and portability. To improve the deposited layer quality, conducting online measurements and feedback control of the dimensions, temperature, and other melt-pool parameters during deposition is essential. Currently, melt-pool dimension measurement is mainly based on machine vision methods, which can mostly detect only the deposition direction of a single melt pool, limiting their measurement range and applicability. We propose a binocular-vision-based online measurement method to detect the melt-pool width during DLD. The method uses a perspective transformation algorithm to align multicamera measurements into a single-coordinate system and a fuzzy entropy threshold segmentation algorithm to extract the melt-pool true contour. This effectively captures melt-pool width information in various deposition directions. A DLD measurement system was constructed, establishing an online model that maps the melt-pool width to the offline deposited layer width, validating the accuracy of the binocular vision system in measuring melt-pool width at different deposition angles. The method achieved high accuracy for melt-pool measurements within certain deposition angle ranges. Within the 30°-60° measurement range, the average error is 0.056 mm, with <3% error. The proposed method enhances the detectable range of melt-pool widths, improving cladding layers and parts.

Lattice-Strained Bimetallic Nanocatalysts: Fundamentals of Synthesis and Structure.

Bimetallic nanostructured catalysts have shown great promise in the areas of energy, environment and magnetics. Tunable composition and electronic configurations due to lattice strain at bimetal interfaces have motivated researchers worldwide to explore them industrial applications. However, to date, the fundamentals of the synthesis of lattice-mismatched bimetallic nanocrystals are still largely uninvestigated for most supported catalyst materials. Therefore, in this work, we have conducted a detailed review of the synthesis and structural characterization of bimetallic nanocatalysts, particularly for renewable energies. In particular, the synthesis of Pt, Au and Pd bimetallic particles in a liquid phase has been critically discussed. The outcome of this review is to provide industrial insights of the rational design of cost-effective nanocatalysts for sustainable conversion technologies.

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.