Pneumococcal vaccination reduces morbidity and mortality among older adults, yet coverage remains suboptimal in China. This study aimed to assess the effectiveness of a pay-it-forward intervention (covering two-thirds of the pneumococcal vaccination cost and offering the option to donate) in increasing pneumococcal vaccination among older adults (aged 60 years or older) in China, compared to standard-of-care self-paid vaccination. We used block randomization (block size = 4) to assign participants to a pay-it-forward arm and a standard-of-care arm in a 1:1 ratio. The primary outcome was pneumococcal vaccination. Secondary outcomes included influenza vaccine uptake, vaccine confidence, successful vaccine referral, and cost-effectiveness. Logistic regression analysis was used to compare PPSV-23 and influenza vaccination coverage and vaccine confidence between the two groups. The cost-effectiveness of the interventions was assessed using a micro-costing approach from the healthcare provider’s perspective. From January to September 2024, 221 older adults were randomized (110 in the pay-it-forward group and 111 in the standard-of-care group). Pneumococcal and influenza vaccine uptake were significantly higher in the pay-it-forward arm (70.9

BackgroundAs a high incidence group, the elderly face the burden of fungal skin diseases, which has remained poorly quantified. This study aims to analyse the spatiotemporal trends in the burden of fungal skin diseases in middle-aged and elderly people from 1990 to 2021.MethodsData were obtained from the Global Burden of Disease (GBD) Study 2021. This study analysed incident cases, prevalent cases, disability-adjusted life years (DALYs), and their corresponding rates for fungal skin diseases in middle-aged and elderly people stratified by sex, age, socio-demographic index (SDI), GBD regions, and countries. Average annual percent change (AAPC) was calculated to assess temporal trends in the burden of fungal skin diseases.ResultsFrom 1990 to 2021, the global incidence, prevalence, and DALYs rates of fungal skin diseases in middle-aged and elderly people were consistently higher than those in the entire population. Globally, incident cases, prevalent cases, and DALYs of fungal skin diseases in middle-aged and elderly people increased by 124.09%, 124.13%, and 123.26%, respectively. In 2021, the incidence, prevalence, and DALYs rates were 38255.44 (95% uncertainty interval [UI]: 32832.61-44492.76), 12186.46 (95% UI: 10721.21-14030.06), and 64.66 (95% UI: 26.34-133.26) per 100,000 population, respectively. From 1990 to 2021, the incidence, prevalence, and DALYs rates exhibited overall upward trends, with AAPCs of 4.12% (95% confidence interval [CI]: 3.04%-5.20%), 4.18% (95% CI: 3.11%-5.24%), and 2.89% (95% CI: 1.89%-3.89%), respectively. Geographically, the highest burden was concentrated in Andean Latin America, Australasia, and Western Europe.ConclusionsThe global burden of fungal skin diseases in middle-aged and elderly people has increased over the past three decades, with significant disparities across sexes, SDI levels, regions, and countries. Targeted public health interventions and resource allocation are required to reduce the burden of fungal skin diseases in this vulnerable population.

Background: Long non-coding RNA (lncRNA) TLR8-AS1 has been implicated in immune regulation, but its role in HIV-1 infection remains unexplored. Methods: TLR8-AS1 expression was assessed in PBMCs and primary monocyte-derived macrophages (MDMs) from HIV-1/AIDS patients and healthy controls. Its subcellular localization was determined via bioinformatics, FISH, and nucleocytoplasmic fractionation. In THP-1-derived macrophages, the functional impact of TLR8-AS1 was evaluated using TLR8-AS1 overexpression and NFAT1-knockdown models; viral replication, inflammatory cytokines, and arachidonic acid (AA) metabolism were analyzed by qPCR, ELISA, and Western blot. Results: TLR8-AS1 expression levels were positively correlated with CD4+ T cell counts (r=0.439, P < 0.05), suggesting a potential association with immune status. In THP-1-derived macrophages, TLR8-AS1 overexpression significantly inhibited HIV-1 p24 production, viral gene (Pol, Vif, Nef, LTR, and Gag) expression, and secretion of IL-1 beta, TNF-alpha, and AA. Mechanistically, cytoplasmic TLR8-AS1 downregulated NFAT1 and PTGS2 (COX-2) expression, selectively suppressing the prostaglandin pathway while leaving the lipoxygenase branch (ALOX5, ALOX15) unaffected. NFAT1 knockdown reproduced the antiviral and anti-inflammatory effects of TLR8-AS1, confirming NFAT1 as a key downstream mediator. In contrast, TLR8-AS1 did not alter TLR8 or its downstream signaling molecules (MyD88 and IRF7), suggesting a TLR8-independent mechanism. Conclusion: TLR8-AS1 restricts HIV-1-induced inflammation and viral replication through the NFAT1-AA axis. These findings identify TLR8-AS1 as a potential therapeutic target for mitigating chronic inflammation and viral persistence in HIV-1 infection.

Human Immunodeficiency Virus (HIV) infection remains a global health challenge, with the roles of N6-methyladenosine (m6A) RNA modification and Transformer 2 Alpha Homolog (TRA2A) in viral regulation yet to be fully elucidated; this study aimed to investigate how TRA2A-mediated m6A modification of Thioredoxin Interacting Protein (TXNIP) regulates macrophage pyroptosis during HIV-1 infection. Lentiviral-mediated knockdown and overexpression of TRA2A were employed to evaluate its effects on TXNIP expression, m6A modifications, and HIV-1 replication, while pyroptosis and inflammatory responses were assessed through LDH release assays, cytokine measurements, and analysis of the NLRP3/Caspase-1/GSDMD signaling pathway. Results showed significant downregulation of TRA2A in macrophages from HIV-1 patients, and TRA2A knockdown promoted viral replication while activating NLRP3/Caspase-1/GSDMD-mediated pyroptosis; mechanistically, TRA2A recognized m6A sites on TXNIP mRNA to reduce its stability, thereby inhibiting inflammasome activation, with these effects reversed by TRA2A overexpression or TXNIP/pyroptosis inhibitors, confirming TRA2A’s critical role in balancing antiviral defense and inflammation control. Collectively, TRA2A functions as an m6A regulator to balance antiviral defense and inflammation via the TXNIP-mediated NLRP3 pathway, establishing a novel regulatory axis and highlighting TRA2A as a potential dual-target therapeutic candidate.

People living with human immunodeficiency virus (HIV) are highly susceptible to opportunistic fungal infections, such as Talaromyces marneffei, Candida, and Pneumocystis jirovecii, primarily due to their immunocompromised status. These infections often manifest as invasive candidiasis, pneumonia, and other severe diseases. Consequently, diagnostic failures for these specific infections remain a leading cause of HIV-related mortality. This review systematically evaluated the currently available diagnostic tools for these pathogenic fungi. Traditionally, etiologic detection, particularly fungal cultivation, has been considered the gold standard for diagnosis. Simultaneously, methods such as microscopic examination, molecular biology tests, and immunological diagnostic technologies are rapidly advancing and becoming increasingly applicable. However, persistent limitations in efficiency, accuracy, reliability, and cost-effectiveness continue to impede clinical diagnosis. This dilemma significantly hampers the advancement of clinical diagnosis for opportunistic fungal infections in HIV-positive populations both in China and globally. Given this diagnostic challenge, there is an urgent need for the further development of novel tools and strategies. These efforts should focus on promoting the identification of molecular targets, innovating targeted probes, exploring detection platforms, and designing diagnostic techniques. Ultimately, improvements in the clinical diagnosis of opportunistic fungal infections will directly contribute to a reduction in the HIV-related mortality rate.

Objective:To compare next-generation sequencing(NGS)and third-generation sequencing(TGS)technologies in HIV-1 subtype determination,drug resistance mutation detection,and identification of high-and low-frequency variants.Methods:A total of 50 newly reported HIV-1-infected cases from Guangxi,China were enrolled.Near full-length genomes were sequenced using both NGS and TGS platforms.Subtype classification,resistance-associated mutations,and mutation frequency distributions were analyzed using appropriate online plat-forms and software.The inconsistent results of subtypes and drug resistance between NGS and TGS were verified by Sanger sequencing.Results:The two sequencing technologies showed good concordance in subtype determi-nation(Cohen's Kappa=0.900,P＜0.001).Among the samples,five were classified as indeterminate by both NGS and TGS,and two showed discordant subtype assignments,primarily involving low-prevalence or recombinant subtypes.TGS identified one additional NNRTI resistance-associated mutation(V179E and V106I)and showed superior performance in detecting complex drug-resistant mutation patterns.There was a difference in the distri-bution of cumulative variant sites across different mutation frequencies identified by the two technologies(χ2=3,771.87,P＜0.001).NGS cumulatively detected 18,367 variant sites(frequency≥5%),with ultra-high-frequency mutations(≥80%)predominating 84.1%.In contrast,TGS cumulatively identified 28,120 variant sites with a fre-quency≥5%,of which ultra-high-frequency mutations accounted for 58.1%.Within the mutation frequency range of 5%-60%,TGS detected a greater number of variant sites than NGS.The overall distributions of cumulative mu-tation site counts at different frequencies detected by the two sequencing technologies were significantly different in samples with concordant subtype classification and in samples with discordant or ambiguous subtype assign-ments(χ2=3,106.93,P＜0.001;χ2=717.26,P＜0.001).Conclusion:NGS and TGS yield consistent results in HIV-1 subtype classification.TGS offers higher sensitivity for complex and low-frequency mutations,while NGS is more stable for ultra-high-frequency variants.

Recombination events are a key driver of human immunodeficiency virus type 1 (HIV-1) genetic diversity. In this study, HIV-1 samples were collected from two male patients in Shenzhen, China. Two novel recombinant forms (Ls6449 and Ls16801) derived from CRF01_AE and CRF07_BC were identified, and their near full-length genomes were obtained. Analysis of these two forms suggested that the recombination between CRF01_AE and CRF07_BC continued to occur in Shenzhen, potentially contributing to the increasing genetic complexity of the local HIV-1 epidemic. These findings highlight the need for enhanced molecular surveillance and genotyping targeting key routes, specifically sexual transmission and mobility-associated spread. It is expected to generate precise epidemiological evidence and inform local HIV prevention and control strategies.

Hand, foot, and mouth disease (HFMD) is a significant infectious condition with no effective therapeutic agents currently available. Previous research has shown that inhibiting m6A can suppress the replication of Enterovirus 71 (EV71), the primary pathogen of HFMD. In this study, we identified a promising compound, AN465, superior to existing m6A inhibitor through a screening of 2.2 million compounds. We conducted a comprehensive validation of AN465 across molecular, cellular, and animal models, confirming its potent inhibitory effects on the replication of both Enterovirus 71 (EV71) and Coxsackievirus A6 (CVA6). Additionally, we elucidated the underlying molecular mechanisms in detail. Overall, this study not only identifies a novel EV71 inhibitor based on targeting the m6A methyltransferase METTL3, but also offers a promising candidate for the first specific therapeutic against EV71 and CA-V6, providing a new strategy for the treatment of HFMD. Hand, foot and mouth disease's main pathogen EV71 can be suppressed by m⁶A inhibition. Here authors identified AN465 as a promising HFMD therapeutic that targets METTL3.

Two novel Gram-stain-positive, non-spore-forming, strictly aerobic, regular rod-shaped bacteria (HY1910T and HY1908) were isolated from bat feces collected from Changshou District of Chongqing City (Altitude: 490 m; N: 30° 02′ 15″, E: 107° 07′ 4″, September 2011) and Chuxiong Yi Autonomous Prefecture, Yunnan province (Altitude: 1795 m; N: 25°09′10″, E: 102°04′39″, October 2013), respectively. Optimal growth is obtained at 28–30 °C (range, 10–37 °C) on BHI-5

This study aims to characterize the epidemiological and clinical features of pulmonary tuberculosis with diabetes mellitus (PTB-DM), identify risk factors for unsuccessful treatment outcomes, and develop predictive models to aid in outcome assessment for these patients. Clinical data from 3886 pulmonary tuberculosis (PTB) cases treated at Liuzhou People’s Hospital Affiliated to Guangxi Medical University between July 2017 and December 2023 were analyzed. A case–control study was conducted to investigate the epidemiological and clinical profiles of PTB-DM. A retrospective cohort study and the LASSO-Logistic regression model were employed to identify independent risk factors for unsuccessful treatment outcomes, and a risk nomogram prediction model was developed to assess the predictive performance of the model. From 2017 to 2023, the rates of diabetes mellitus among pulmonary tuberculosis patients were 7.14

Long-term non-progressors (LTNPs) provide key insights into HIV-1 pathogenesis and potential functional cure strategies. Whether viral evolution persists in LTNPs remains debated. Previous studies have mainly focused on partial HIV-1 genome fragments using single-gene amplification. In contrast, our study employs near full-length bulk next-generation sequencing (NGS) to investigate viral quasispecies evolution, diversity, and CTL-associated mutations at the nucleotide level, offering new perspectives on intra-host viral dynamics. Blood samples of two LTNPs were collected at four time points over a approximately 2 years. The HIV-1 near full-length genome of plasma RNA and proviral DNA were amplified, and bulk NGS was performed. Consensus sequences were used for phylogenetic analysis and divergence calculation. Intra-host single-nucleotide variants (iSNVs), amino acid variations, and mutations in CTL epitopes were also analyzed. Both LTNPs displayed limited evolution over time, as identified from the phylogenetic tree and genetic distance, with higher divergence observed in DNA sequences than in RNA sequences. Evolutionary divergence was observed between HIV-1 plasma RNA and proviral DNA sequences. Intra-host diversity indices, including the number of iSNVs and Shannon entropy, also indicated greater diversity in DNA sequences than in RNA sequences. A considerable number and high frequency of mutations in CTL were identified consistently both in DNA and in RNA sequences, which showed slight frequency changes over time. These findings support the limit HIV-1 evolution in LTNPs and greater intra-host diversity of proviral DNA than plasma RNA. Our findings also suggest substantial, high-frequency, and sustained mutations in CTL epitopes in LTNPs with a relatively high level of viral replication despite optimal immune control.IMPORTANCELong-term non-progressors (LTNPs) are a rare group of HIV-1-infected individuals who maintain stable CD4+ T cell counts and low viral loads in the absence of antiretroviral therapy. Understanding the virological and immunological mechanisms underpinning this phenotype could inform strategies for functional cure. Using bulk next-generation sequencing of near full-length genomes of both HIV plasma RNA and proviral DNA over multiple time points, our study provides high-resolution insights into intra-host viral evolution in LTNPs. We reveal limited viral evolution and divergence between plasma RNA and proviral DNA. Higher diversity was found in proviral DNA than in plasma RNA, contributed by a substantial number of low-frequency mutations. HLA-restricted CTL escape mutations were stable and maintained at high frequency across all time points. These results challenge the notion of viral stasis in LTNPs and underscore the complex interplay between viral persistence and immune control, offering critical clues for vaccine design and reservoir-targeting therapeutic approaches. These findings support the hypothesis that LTNPs maintain durable viral control and non-progressive disease by achieving a balance between viral evolution and immune containment.

The Guangxi Zhuang Autonomous Region (Guangxi), located at the junction of Southwestern and Southern China, is a region with a high prevalence of human immunodeficiency virus type 1 (HIV-1). Understanding the genomic features and transmission dynamics of circulating HIV-1 strains is crucial for effective epidemic control. This study aimed to analyze the near-full-length genomic (NFLG) characteristics, recombination patterns, and cross-provincial transmission relationships of the newly reported recombinants CRF120_0107 and CRF149_01B in Guangxi. We selected six near-full-length HIV-1 genomic sequences (8,483–8,732 bp) from the entire study containing 508 samples collected from 2019 to 2024 in Nanning and Baise, Guangxi. Phylogenetic analysis revealed that samples GX.NN55.HET.2024, GX.NN152.MSM.2019, and GX.NN130.HET.2024 clustered into the same branch as the CRF120_0107 strain reported in Guangdong Province in October 2022. Recombination breakpoint analysis showed that CRF120_0107 was formed by recombination between CRF07_BC and CRF01_AE. Samples GX.BS401.HET.2024, GX.NN59.HET.2024, and GX.NN118.HET.2024 were highly homologous to the CRF149_01B strain reported in Yunnan Province in April 2025, which was recombined from CRF55_01B and subtype B. Sub-region phylogenetic analysis further confirmed that each fragment clustered with the corresponding subtype reference strain (bootstrap values > 90%). The first identification of CRF120_0107 and CRF149_01B strains in the Guangxi region based on six sequences suggests cross-provincial transmission of HIV-1 recombinant strains, highlighting the importance of molecular surveillance and targeted interventions to control viral spread.

The maintenance of normal CD4+ T cell levels in human immunodeficiency virus (HIV) infected long-term non-progressors (LTNPs) remains elusive. N6-methyladenosine (m6A) regulates RNA metabolism and immune function, but its role in LTNP pathogenesis is unelucidated. This study integrated in vivo analyses of peripheral blood mononuclear cells (PBMCs) from LTNPs, typical progressors (TPs), ART-treated patients, and healthy controls with in vitro experiments using the MT2-HIV-1ⅢB model to explored the m6A regulatory role in LTNPs. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) identified uniquely elevated m6A modification abundance and METTL3 expression in LTNPs vs. TPs. Differential m6A and mRNA analysis bighlighted enrichment of innate immunity/inflammation pathways, particularly the SOCS/IL/JAK axis. Further experiments confirmed that METTL3 mediates m6A modification of SOCS3, which suppresses JAK2/STAT4 phosphorylation to modulate IL-12/IFN-γ/IL-4 expression. These findings uncover a novel m6A-METTL3-SOCS3 regulatory axis underlying HIV long-term non-progression, explaining preserved CD4+ T cell homeostasis in LTNPs. IMPOTANCE LTNPs represent a unique subset of HIV-infected individuals who naturally maintain normal CD4⁺ T cell levels and slow disease progression, offering a valuable model to dissect host protective mechanisms against HIV. m⁶A modification has emerged as a pivotal regulator roles in HIV replication and T cell activation, yet its contribution to LTNP biology has remained unclear. This novel mechanism provides a potential explanation for the maintenance of normal CD4+ T cell levels in LTNPs. Our findings shed light on the molecular basis of HIV-1 long-term non-progression and offered crucial insights for developing functional cure for AIDS and new host immune strategies.

HIV-1 infection leads to metabolic changes in macrophages, yet a comprehensive understanding of its pathogenesis remains limited. To address this, we integrated transcriptomic and metabolomic analyses to uncover intracellular metabolic alterations in HIV-1-infected macrophages. We identified differentially expressed genes (DEGs) using RNA-sequencing, while metabolomic profiling was performed with UHPLC-QE-MS. The integration of transcriptomics and metabolomics was achieved through “Joint Pathway Analysis,” and reverse transcription-quantitative PCR (RT-qPCR) was used to validate the identified pathways. Our transcriptomic analysis revealed a total of 890 DEGs, comprising 424 downregulated and 466 upregulated genes in macrophages infected with HIV-1. KEGG enrichment analysis highlighted the biosynthesis of amino acids and glycine, serine, and threonine metabolism as significantly enriched (P < 0.05). RT-qPCR results confirmed the expression of key genes, including PHGDH, PSAT1, PSPH, CBS, CTH, and AOC2, associated with these pathways. From the metabolomic analysis, we identified 60 differential metabolites, with glycerophospholipids representing the majority (51.67

ABSTRACT Long-term non-progressors (LTNPs) represent a valuable model to investigate immunological features associated with non-progression in chronic HIV infection. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells obtained from 12 individuals, including 4 LTNPs, 4 typical progressors (TPs), and 4 healthy donors (HDs). Compared with TPs, LTNPs exhibited a higher percentage of naive T cells, whereas TPs showed a higher percentage of CD8+ Effector-GNLY cells. LTNPs also exhibited lower gene-expression scores related to T-cell activation, cytotoxicity, inflammation, and interferon-alpha response across multiple effector-state T-cell subsets. GO enrichment analysis showed that compared with HDs and TPs, LTNPs exhibited downregulation of migration, translation, and antiviral response pathways in both CD4+ and CD8+ T cells, with upregulation of stress/inflammatory response and differentiation programs in CD4+ T cells and of immune differentiation/activation pathways in CD8+ T cells. High-dimensional weighted gene co-expression network analysis (hdWGCNA) further revealed higher module eigengene expression of innate and myeloid-related modules and lower expression of B-cell and cytotoxicity-related modules in LTNPs compared with TPs. Additionally, HIV-1 RNA+ cells were detected more frequently in TPs than in LTNPs and predominantly identified within CD4+ T cells. Together, these findings reveal a transcriptionally balanced and favorable immunological profile associated with non-progressive HIV infection and inform the design of immune-based strategies toward a functional HIV cure.IMPORTANCEUnderstanding molecular traits associated with natural control in LTNPs is critical for advancing HIV remission and cure strategies. Using single-cell RNA sequencing, we found that LTNPs had more naive T cells and fewer CD8+ effector-GNLY cells than typical progressors, along with lower activation, cytotoxicity, inflammation, and IFN-α scores across effector-state T-cell subsets. Differential expression and GO analyses showed predominant downregulation of migration, translation, and antiviral pathways, while preserving early activation markers. Co-expression network analysis revealed higher innate/immune-regulatory module activity and lower B-cell and cytotoxicity modules in LTNPs. HIV-1 RNA+ cells were detected less frequently in LTNPs and mainly detected in CD4+ T cells. These findings highlight balanced immune programs in LTNPs, which may inform strategies toward a functional HIV cure.

Post-translational modifications (PTMs) regulate protein structure, function, and interactions, playing pivotal roles in cellular processes and disease progression. Lactate, a byproduct of the Warburg effect, accumulates excessively during viral infections and functions as a signaling molecule, disrupting mitochondrial antiviral-signaling protein activity and facilitating viral immune evasion. Lactylation, a recently identified PTM derived from lactate metabolism, links cellular metabolism and immune regulation by modulating gene expression and metabolic reprogramming. It also serves as a mechanism for viruses to modulate host immunity. Despite its emerging importance, its role with respect to viruses infecting humans and animals remains poorly understood. Investigating its impact on metabolic, protein modifications, and immune signaling may reveal novel immune evasion strategies and therapeutic targets. This review aims to provide an overview of the fundamental features and regulatory functions of lactylation, explore its association with viral infections, and offer insights into how lactylation influences metabolic and immune responses during virus-host interactions.

Talaromyces marneffei (T. marneffei) is an opportunistic, dimorphic fungus that has been clinically reported to involve the central nervous system (CNS). However, its neuroinvasive capacity and the underlying pathogenic mechanisms remain poorly understood. In this study, T. marneffei infection was found to impair learning, memory, and motor balance in mice, as demonstrated by Morris water maze and accelerating rotarod assays. Viable T. marneffei was subsequently isolated from hippocampus and cortex through fungal cultures, confirming its ability to invade the CNS. Histopathological analysis revealed CNS damage following infection, characterized by neuronal pyknosis, neurofibrillary tangles, and an increased presence of glial cells in the cortex. To investigate the underlying mechanisms, transcriptomic profiling showed significant enrichment of neurodegeneration pathways, with elevated Tau and GSDMD expression in hippocampal and cortical regions as well as N2a cells. Additionally, neuronal damage was exacerbated by indirect neurotoxicity mediated by microglial M1 polarization, accompanied by increased levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). In conclusion, our findings uncover for the first time a dual-pathogenic mechanism by which T. marneffei induces CNS injury: direct neuronal damage via Tau pathology and GSDMD-dependent pyroptosis and indirect inflammation-mediated injury via M1-polarized microglia. These insights not only advance our understanding of fungal neuroinvasion but also provide a foundation for the development of targeted therapies.

BACKGROUND:Dengue remains a significant public health threat, yet the disease burden among the elderly has remained poorly quantified. This study aims to analyse the spatiotemporal trends in the dengue burden among the elderly at global, regional, and national levels from 1990 to 2021. METHODS:Data on the dengue burden were obtained from the Global Burden of Disease (GBD) 2021 study. This study described the incident cases, deaths, disability-adjusted life years (DALYs), and corresponding rates for dengue among adults aged 70 years and above in 1990 and 2021 by sex, age, socio-demographic index (SDI), GBD region, and country. Joinpoint regression analysis was employed to assess the temporal trends in dengue burden from 1990 to 2021. RESULTS:Between 1990 and 2021, the global incidence and DALYs rate of dengue among the elderly were lower than those in the entire population, whereas the mortality rate remained consistently higher. During this period, the incident cases, deaths, and DALYs for dengue worldwide increased by 372.69%, 439.15%, and 404.06%, respectively. In 2021, the global incidence, mortality, and DALYs rates of dengue among the elderly were 666.10, 1.28, and 23.92 per 100 000 population, respectively. From 1990 to 2021, the incidence, mortality, and DALYs rates of dengue showed an overall upward trend, with average annual percentage changes of 2.11 (95% confidence interval [CI]: 1.88-2.35), 2.58 (95% CI: 2.02-3.14), and 2.35 (95% CI: 2.20-2.69), respectively. Regionally, the highest incidence, mortality, and DALYs rates occurred in low-middle SDI regions. The highest dengue burden was primarily concentrated in Tropical Latin America, South Asia, and Southeast Asia. CONCLUSIONS:The dengue burden among adults aged 70 years and above has significantly increased over the past three decades, with substantial variations across SDI levels, regions, and countries. Targeted measures, including developing clinical management guidelines, enhancing vaccine research, and conducting community education, are urgently needed to reduce the burden in this vulnerable population.

One of the unknowns related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the mechanism underlying the inflammatory response induced by the virus. Poly(A) polymerase gamma (PAPOLG) was previously shown to be upregulated during SARS-CoV-2 infection. The present study explored how PAPOLG affects the inflammatory reaction triggered by SARS-CoV-2. PAPOLG was knocked down or overexpressed in THP-1 macrophages. Target pathways were identified using RNA sequencing and bioinformatics analysis. The levels of PAPOLG, transcriptional regulator nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and cytokines TNF-α and IL-6 were measured, along with an assessment of NF-κB mRNA stability. PAPOLG was significantly upregulated in SARS-CoV-2-infected THP-1 macrophages. Genes subjected to alternative polyadenylation were enriched in immune pathways, and NF-κB emerged as a key regulator. Knockdown of PAPOLG promoted NF-κB mRNA degradation, while decreasing the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL6). Conversely, overexpression of PAPOLG stabilized NF-κB mRNA and enhanced TNF-α and IL-6 expression. PAPOLG contributes to the inflammatory response in SARS-CoV-2-infected macrophages by stabilizing NF-κB mRNA. Thus, PAPOLG may be targeted to control COVID-19-related inflammation.