搜索结果：Molecular biology research communications

Recent molecular phylogenetic analyses within the tribe Arabideae (Brassicaceae) have uncovered unresolved lineages that challenge current generic boundaries. In this study, we incorporate molecular data with morphological evidence to resolve a long-standing taxonomic ambiguity, resulting in the description of a new monophyletic genus, Hafezia gen. nov., together with two new combinations, H. aucheri (Boiss.) A.R. Khosravi & A. Eslami-Farouji and H. parvula (Dufour ex DC.) A.R. Khosravi & A. Eslami-Farouji. Integrative taxonomy and phylogenetic insights, such as indels and substitution nucleotide variants, confirm the distinct assignment of these taxa, previously misassigned to Arabis L. Morphological reassessment, including traits such as simple, long setaceous hairs, notched petals, winged stamens, not compressed, not subtorulose or torulose fruits, supports their separation. The new genus naturally grows in the Mediterranean and west of the Irano-Turanian floristic regions. Our findings highlight the significance of integration of taxonomic investigations with the molecular investigations in clarifying evolutionary relationships and provide a revised key for accurate identification within Arabideae.

Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses along a continuum from simple steatosis to steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. However, current clinical and research frameworks rely primarily on static, histology-defined stages that fail to capture the continuous nature of disease progression. Here, we present a data-driven framework that reconstructs MASLD progression as a continuous molecular trajectory from cross-sectional liver transcriptomic profiles. By positioning patients along this trajectory, we move beyond conventional stage-based classifications and resolve the ordered activation of regulatory programmes, signalling pathways and cellular remodelling processes underlying disease progression. To enable non-invasive patient stratification, we integrate the inferred molecular trajectory with paired liver-plasma proteomics data and identify a 57-gene plasma-accessible biomarker panel that accurately predicts advanced fibrosis and continuously positions patients along the disease trajectory across independent cohorts, outperforming established non-invasive clinical scores. Together, this work establishes a generalizable trajectory-based framework for understanding MASLD pathophysiology and provides a foundation for mechanistically informed biomarker discovery, precision staging and stage-aware therapeutic prioritization.

Ectodomain shedding, a post-translational process mediated primarily by A Disintegrin And Metalloprotease (ADAM) family members, represents a fundamental mechanism regulating intercellular communications. By cleaving the extracellular domains of membrane-anchored cytokines, receptors, growth factors, and adhesion molecules, ADAM proteases dynamically shape cytokine signaling networks that underpin immune regulation, inflammation, and tissue homeostasis. Among these enzymes, ADAM10 and ADAM17 are key effectors whose tightly controlled activity ensures the fine-tuning of pro- and anti-inflammatory pathways. Dysregulated ADAM function perturbs cytokine gradients and receptor availability, contributing to the pathogenesis of cancer, autoimmune disorders, and chronic inflammatory diseases. In this review, we provide updated perspectives on the mechanisms governing ADAM activation and substrate selectivity, including prodomain processing, trafficking, interaction with protein partners, and modulation by inflammatory stimuli. We further highlight species-specific differences and genetic polymorphisms that influence ADAM expression and catalytic efficiency, emphasizing their translational relevance in precision medicine. Collectively, delineating the ADAM/cytokine signaling axis offers crucial insights into immune homeostasis and unveils novel opportunities for therapeutic intervention in cancer and immune-mediated diseases.

Clear cell renal cell carcinoma (ccRCC) is largely driven by the transcription factor hypoxia-inducible factor 2α (HIF-2α)1. Here we show that monotherapy with casdatifan-an orally bioavailable, potent and selective HIF-2α inhibitor2-produces meaningful, durable antitumour activity with manageable safety in individuals with refractory metastatic ccRCC. Dose-expansion data from the ARC-20 study ( NCT05536141 ) are presented, including for the 100 mg once daily (QD) cohort (n = 32) and the total cohort (n = 127). Treatment discontinuation from casdatifan-related adverse events was infrequent (3%), and class-effect toxicities included anaemia and hypoxia. The confirmed objective response rates (ORRs) were 35% (95% confidence intervals (CI) = 19-55%; 100 mg QD) and 31% (95% CI = 23-40%; total); median progression-free survival (PFS) was not estimable (95% CI = 5.7-not estimable; 100 mg QD) and 12.2 months (9.4-20.6; total). Greater maximal reductions in serum erythropoietin were associated with improved clinical outcomes, including a higher ORR (P = 0.001), lower rates of progressive disease (P = 0.003) and longer PFS (P = 0.006). Erythropoietin expression was restricted to cancer cells and was significantly higher at the mRNA level in patients with clinical benefit. Concordantly, HIF-2α protein expression and HIF-2α expression signature were associated with prolonged PFS. Overall, our findings show that casdatifan achieves meaningful, durable responses with manageable safety. These data establish a link between on-target HIF-2α pathway modulation, tumour biology and clinical efficacy.

Low Ki67 after short preoperative endocrine therapy (ET) indicates a favorable prognosis in hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC). We investigated predictors of ET response in the West German Study Group (WSG) ADAPT-HR+/HER2- and ADAPTcycle trials. ET response (Ki67 &#x2264;10%) after 2- to 4-week standard ET, recurrence score (RS), and nodal status were used for treatment allocation. In ADAPT-HR+/HER2-, patients at high clinical risk received ET alone if N0-1 and RS 0-11 or RS 12-25 and ET response. In ADAPTcycle, N0-1 patients with RS > 25 and ET response and those with RS < 25 and e.g. ET nonresponse, N2-3 patients with RS &#x2264; 25 and ET response, were randomly assigned to receive (neo)adjuvant chemotherapy or aromatase inhibitor (AI)+ribociclib. Predictors of ET response were identified through multivariable logistic regression models. Three thousand six hundred seventy-five patients from the ADAPT-HR+/HER2- cohort (&#x2264;50 years and premenopausal, &#x2264;50 years: N = 1250; >50 years or postmenopausal, >50 years: N = 2425) and 4239 from the ADAPTcycle screening cohort (&#x2264;50 years: N = 1336; >50 years: N = 2903) were analyzed. ET response rates were higher after AI (ADAPT-HR+/HER2-/ADAPTcycle: 81.4%/76.7%) versus tamoxifen (ADAPT-HR+/HER2-/ADAPTcycle: 40.1%/34.7%) in both age groups, with further improvement by ovarian function suppression (OFS) in premenopausal patients. Premenopausal patients with GnRH plus AI had similar ET response rates as postmenopausal patients. ET response predictors included AI use (plus OFS in premenopausal), age >50 years, lower RS and baseline Ki67 levels, and higher expression of estrogen receptor (by immunohistochemistry) and HER2 (by Oncotype DX&#x2122;). In ADAPT-HR+/HER2-, 5-year distant disease-free survival in ET responders was markedly higher than in nonresponders and also in chemotherapy-treated N0-1 patients with RS > 25 (87.0 versus 80.7%), and it was only slightly lower than that in the RS 12-25 group. We observed similar ET response rates in two large phase III trials. Postmenopausal patients (mostly receiving AI) had higher ET response rates than younger patients. However, young patients with GnRH+AI had ET response rates comparable with those of postmenopausal patients, suggesting that therapy rather than biology accounts for the difference. Combining ET response and gene expression assessment could help more patients with luminal eBC avoid chemotherapy.

Climate change amplifies many threats to human health. Despite advances in understanding climate change dynamics and impacts, there remains a critical gap in translating scientific knowledge into equitable, and community-driven health interventions. The inaugural One Earth, One Health workshop sought to explore this gap through human-centered design exercises involving interdisciplinary researchers from climate and Earth sciences, engineering, epidemiology, microbiology, and environmental health. Although participants did not co-develop solutions with affected communities, they used stakeholder role-playing to guide ideation and lay groundwork for actionable plans. Through these methods, participants identified community needs and proposed prototype solutions to alleviate health threats exacerbated by global environmental change. Prototypes were organized around infectious diseases, extreme weather, and air quality, as illustrative themes rather than an exhaustive set of risks. Key solutions included strategies for anticipatory systems and early warning (e.g.,&#xa0;integrating environmental signals with health data), inclusive communication and infrastructure needs for responding to extreme weather events, and integrated platforms visualizing air quality trends to support tailored, context-aware guidance beyond one-size-fits-all alerts. The workshop highlighted opportunities such as leveraging machine learning, Earth observation, and real-time surveillance to protect communities, but also noted barriers including data quality, technological redundancy, privacy, and governance challenges. Additionally, participants emphasized the need for interdisciplinary teams capable of collaborating across sectors, breaking down silos and addressing gaps in training and education. Overall, the workshop illustrates how process-driven, human-centered approaches can help surface user needs and generate testable prototype concepts, while underscoring the importance of direct community partnership for implementation. Climate and other environmental changes amplify threats to human health, such as extreme weather events, infectious diseases, and poor air quality. When trying to understand which hazards and exposures pose the risk to human health, which populations are most vulnerable, and what interventions might be most protective, scientists rely on hypothesis&#x2010;driven approaches. Such approaches may not directly reflect the lived experiences or priorities of affected communities. The One Earth, One Health workshop congregated researchers across disciplines to test a method called human&#x2010;centered design. Although this workshop did not include direct participation from every key stakeholder groups, participants role&#x2010;played as community members, such as healthcare workers, city planners, parents, and concerned citizens, to simulate more inclusive solution development. Participants discussed and co&#x2010;developed early&#x2010;stage, user&#x2010;centered solutions, such as better disease prediction tools, clearer emergency communications, and unified platforms for air quality monitoring and alerts. Although promising, the solutions face multiple challenges, including limitations in data availability, timeliness, and interoperability and technological complexity. The workshop underscored the importance of collaboration and co&#x2010;creation as guiding principles for future climate&#x2010;health research and intervention design, including the need to engage researchers, policymakers, healthcare workers, and communities in subsequent phases to support practical, equitable, and beneficial outcomes.

The effect of 4-OH-Coumarin, a warfarin derivate, on the cellular characteristics and metastasis of SH-SY5Y neuroblastoma cells and HUVEC cells was aimed to determine. After IC50 concentrations were detected wound healing and hematoxylin-eosin assays were performed on both cell lines. Ki-67, hTERT, PI3K, AKT, mTOR, HIF-1&#x3b1;, PINK1, Parkin, Cyt C, p53 gene expressions and piR-651, piR-823, miR-126 expressions were determined by RT-PCR. The proliferation, wound closure and survival decreased after 4-OH-Coumarin treatment (p<0.001). Ki-67, hTERT, PI3K, mTOR, HIF-1&#x3b1;, PINK1, Parkin, Cyt C and piR-823 expressions were decreased, while AKT, p53, piR-651, and miR-126 increased on SH-SY5Y (p<0.001). AKT (p<0.05), Parkin, and piR-651 expressions increased on only HUVEC cells (p<0.001). We believe that the study of various molecules that are secondary metabolites such as 4-OH-Coumarin may provide valuable data to observe the effects and mechanisms of new therapeutics that have the potential to be used for cancer treatment.

Active learning has emerged as an effective strategy for accelerating molecular discovery under limited labeling budgets. However, existing methods primarily focus on global information, often overlooking activity cliff-sharp changes in bioactivity caused by small structural perturbations-leading to suboptimal sample selection. In this work, we propose a model-agnostic, activity cliff-aware active learning framework designed to improve hit discovery efficiency without imposing constraints on the underlying molecular representations. Our framework introduces an auxiliary activity cliff scoring module trained on pairwise molecular relationships to explicitly capture local structure-activity sensitivity. The outputs of this module are integrated into a cliff-aware acquisition function that prioritizes structurally informative molecules whose labels are expected to be most beneficial for model improvement. Notably, the proposed strategy is agnostic to backbone architectures and molecular feature, enabling seamless integration with a wide range of existing active learning pipelines. We evaluate our approach on multiple benchmark datasets under a fixed labeling budget. Across all targets, the proposed method consistently identifies more active compounds than baseline acquisition strategies, demonstrating improved robustness in early-stage, data-scarce learning scenarios. Ablation studies further confirm the contribution of activity cliff awareness to the observed performance gains. Overall, our results underscore the importance of explicitly modeling activity cliffs within active learning frameworks and highlight the effectiveness of a model-agnostic design for accelerating hit discovery in data-limited drug discovery settings. The source code is accessible online at https://github.com/wnsgk/AC-Active.

The 9th National Congress of the Italian Society for Virology (SIV-ISV), entitled "One Virology-One Health", took place in Turin at the Centro Congressi Lingotto from 22 to 24 June 2025. The meeting highlighted recent multidisciplinary and translational developments in virology, with a strong focus on the integration of the One Health perspective. Major themes included viral emergence and surveillance, genomic sequencing and bioinformatics, virus-host interactions, viral immunology and vaccines, structural and physical virology, environmental and food virology, zoonoses and animal infections, diagnostics and antiviral therapy, virus-based biotechnology and plant virology. The Congress aimed to: (i) bring together clinicians, basic researchers, veterinarians, environmental microbiologists, bioinformaticians, public-health professionals and industry to share methodologies and best practices; (ii) provide an interactive scientific environment promoting discussion and collaboration between senior investigators and trainees through plenaries, joint society sessions, invited talks, oral communications selected from abstracts, poster sessions, and mentoring panels; and (iii) identify priorities and inspire new research directions at the interface of human, animal and environmental health. More than 400 participants from national and international institutions attended the meeting, featuring distinguished plenary speakers, joint sessions with global networks, and numerous presentations of original unpublished data. This report summarizes the meeting's scientific highlights, cross-disciplinary discussions, and proposed actions to strengthen One Health surveillance, computational infrastructures, and translational applications of viral biology.

The International Union of Biochemistry and Molecular Biology Trainee Initiative supports early-career researchers globally. This overview covers what researchers gain from the initiative, such as funding pathways, science communication training, and strategies for building a professional network, thereby illustrating how the Trainee Initiative empowers trainees' career development.

Hepatocellular carcinoma frequently exhibits evasion of apoptosis, rendering the anti-apoptotic Bcl-2 protein a pertinent therapeutic target. Steroids from Talaromyces stipitatus were evaluated as Bcl-2 inhibitors using molecular docking, molecular dynamics simulation, MMGBSA free-energy estimation, ADMET prediction, and DFT descriptors. Docking prioritized CPD2 over Paclitaxel. It also indicated accommodation within a conserved pocket supported by hydrogen-bond and hydrophobic interactions. Molecular dynamics suggested sustained stability and compactness for the CPD2-Bcl-2 complex. In contrast, the reference complex exhibited comparatively larger conformational excursions. MMGBSA favored CPD2, with improved net association attributable primarily to a reduced solvation penalty. ADMET profiling indicated limited aqueous solubility and a shared hERG II liability, while predicting no hepatotoxicity alert for CPD2. DFT descriptors were consistent with higher electronic responsiveness for CPD2 relative to the reference. These findings suggest that CPD2 may serve as a promising scaffold for developing Bcl-2-targeted therapeutic strategies against HCC. Future in vitro and in vivo studies are required to validate these computational predictions and guide lead optimization.

One ubiquitous pattern of organismal form that has long fascinated biologists is the covariation of seemingly unrelated traits across the body. This has led many to study phenotypic integration-the tendency of a biological or developmental system to give rise to such correlations. While integration has been observed across broad phylogenetic and broad temporal scales, our understanding of the underlying mechanisms is limited to broad categories of causation, such as development and selection. However, we believe that developing a more granular understanding of these mechanisms will be critical to more fully elucidate the evolutionary consequences of integration and to resolve past discrepancies in empirical data. To this end, we offer a list of intrinsic and molecular mechanisms that we hypothesize could drive integration of organismal form. We also present a list of biological processes, the set of intra- and inter-individual interactions affecting an organism, which may shape the deployment of these intrinsic mechanisms. Finally, we discuss how understanding these mechanisms could lead to different predictions about the temporal patterns of integration and even the evolvability of a system. Neither our list of mechanisms, nor our proposed consequences, are comprehensive; rather we hope that this discussion will encourage evolutionary and molecular biologists alike to build a deeper mechanistic understanding of organismal covariation, from cell-cell communications to macroevolutionary trends.

Supratentorial ependymomas frequently harbor ZFTA-RELA (ZRfus) gene fusions that initiate oncogenic transcriptional programs; however, the downstream post-transcriptional regulatory mechanisms remain poorly understood. This study aimed to elucidate the contribution of microRNAs (miRNAs) to the aggressive phenotype characteristic of ZRfus&#x202f;+&#x202f;tumors. Small RNA sequencing was performed on fusion-positive (ZRfus+) and fusion-negative (ZRfus-) supratentorial ependymomas, followed by integrative bioinformatic analyses. Differentially expressed miRNAs and their predicted mRNA targets were validated using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Associations with clinical outcomes were evaluated through progression-free survival (PFS) analysis. Distinct miRNA expression profiles discriminated ZRfus+ from ZRfus- tumors. ZRfus&#x202f;+&#x202f;tumors demonstrated significant upregulation of hsa-miR-138-5p and downregulation of hsa-miR-135b-5p and hsa-miR-216a-3p. Target prediction and pathway enrichment analyses identified TERT, YAP1, RELA, and TP53 as key dysregulated network nodes. Functionally, ZRfus+ tumors exhibited enhanced epithelial-mesenchymal transition (EMT) and stemness signatures, marked by upregulation of SNAIL, SLUG, Nestin, and N-Cadherin. Clinically, ZRfus&#x202f;+&#x202f;status correlated with significantly shorter progression-free survival, underscoring its adverse prognostic significance. This study delineates a distinct ZR fus-associated miRNA landscape in supratentorial ependymomas, implicates hsa-miR-138-5p as a potential biomarker of oncogenic signaling and EMT activation, and reveals mechanistic links between fusion-driven transcriptional dysregulation and tumor aggressiveness. These findings lay the groundwork for miRNA-based therapeutic strategies in high-risk pediatric ependymoma subtypes. Supratentorial ependymomas with ZFTA-RELA fusions represent a highly aggressive pediatric brain tumor subtype, yet the post-transcriptional mechanisms driving their malignancy remain unclear. This study fills a critical gap by systematically profiling miRNA expression in fusion-positive and fusion-negative supratentorial ependymomas, revealing a distinct fusion-associated miRNA signature. The identification of hsa-miR-138-5p upregulation and hsa-miR-135b-5p/hsa-miR-216a-3p downregulation, converging on key oncogenic nodes such as TERT, YAP1, RELA, and TP53, provides novel mechanistic insight into how fusion-driven miRNA dysregulation enhances epithelial-mesenchymal transition and stemness. The findings suggest that miRNA-fusion interactions play an important role in tumor aggressiveness and highlight hsa-miR-138-5p as a potential biomarker for disease progression. Clinically, the work advances understanding of fusion-driven ependymoma biology and lays the foundation for developing miRNA-based diagnostic and therapeutic strategies targeting molecular mechanisms of tumor progression.

Sirtuin 1 (SIRT1), an NAD&#x207a;-dependent deacetylase, is involved in glucose homeostasis, insulin signaling, and inflammatory regulation, making it a potential molecular target in type 2 diabetes mellitus (T2DM). This case-control study investigated the association between serum SIRT1 levels, the SIRT1 promoter polymorphism rs7895833, and metabolic parameters in 150 patients with T2DM and 150 age- and sex-matched healthy controls. Serum SIRT1 concentrations were measured by ELISA, and rs7895833 genotyping was performed using allele-specific PCR. Clinical and biochemical variables were also assessed. Serum SIRT1 levels were significantly lower in patients with T2DM than in controls (p < 0.001) and showed significant inverse correlations with fasting plasma glucose (p = 0.001) and HbA1c (p < 0.001). Genotypic analysis revealed a significant difference in the distribution of the rs7895833 AG genotype between the two groups (p = 0.03), and under the overdominant model (AG vs. AA + GG), the heterozygous AG genotype was significantly associated with T2DM risk (OR = 1.81, p = 0.011), whereas no significant association was found between SIRT1 genotypes and circulating SIRT1 levels. These findings suggest that reduced SIRT1 is associated with hyperglycemia and poor glycemic control in T2DM. Overall, SIRT1 may serve as a potential biomarker and molecular mediator in T2DM pathogenesis. This study provides original data from a Middle Eastern population and may help inform future mechanistic and comparative studies.

Organisms rely on coordinated stress responses to maintain cellular homeostasis. Perhaps the best-known example of multiple stress inputs converging onto a single response is the integrated stress response, which reduces global translation under various stressed conditions to reduce the protein folding burden of the cell. Similarly, most stress responses generally involve coordination of additional protein homeostasis (proteostasis) pathways, including increased expression of chaperones to refold proteins, as well as activation of clearance mechanisms, such as autophagy and the ubiquitin proteasome system. Our study investigates how heat stress can influence coordinated activation of both cytosolic and endoplasmic reticulum (ER) chaperones, exploring bidirectional cross talk between canonical activators of the cytosolic heat-shock response (HSR) and the unfolded protein response of the ER (UPRER). Using robust transcriptional reporters in the Caenorhabditis elegans model system, we explore a noncanonical activation of the UPRER under heat stress by the coordinated effects of XBP-1 and HSF-1. We further investigate inter-tissue communications of stress whereby neuronal or glial activation of the UPRER can result in heterotypic enhancement of the HSR in peripheral cells and can increase thermotolerance. This work highlights the complex convergence of cellular stress responses, a phenomenon that may reflect a general strategy wherein localized stress can activate numerous proteostasis pathways to prevent whole-cell and whole-organism damage.

Background/Objectives: Pediatric asthma remains a pressing public health issue, especially among low-income, minority children living in subsidized housing. Methods: This study employed a community-based participatory research approach to explore barriers and potential solutions for improving asthma management in this vulnerable population. Semi-structured interviews were conducted with 22 caregivers of children with asthma and 8 community health workers in Washington, DC-a city marked by high childhood asthma rates and concentrated subsidized housing. Results: Thematic analysis identified six core findings: (1) families frequently encountered multiple home environmental asthma triggers, including pests, mold, secondhand smoke, leaks, poor ventilation, and aging infrastructure; (2) healthy housing services were under implemented, often due to unresponsive landlords, inadequate inspections, and poor maintenance; (3) existing services such as pest control, mold remediation, and smoke-free policies were ineffectively implemented; (4) challenges to service delivery included difficulties faced by landlords and structural barriers tied to geography, race, and socioeconomic status; (5) substandard housing conditions contributed to residents' feelings of powerlessness, frustration, and distrust, with some taking legal action to address persistent hazards; and (6) participants recommended stronger housing code enforcement, sustained funding for home-based environmental interventions, housing-health liaisons, strengthened landlord accountability, support for landlords to facilitate repairs, centering families' voices, and advocacy. Conclusions: This study underscores the persistent challenges caregivers face in managing asthma triggers in subsidized housing. The findings highlight the critical need for improved housing conditions, greater landlord and housing authority accountability, and policy reforms to ensure consistent, equitable, and sustainable healthy housing services that reduce pediatric asthma disparities.

Psoriasis patients were 4- 5 times more likely to have S. aureus colonize their skin. Psoriasis is caused by staphylococcal infection-induced keratinocyte death, which is maintained by elevated cytokine production of TNF-&#x3b1; and IFN-&#x3b3;. The study sought to determine the association between the influence of gene expression of certain genes in psoriasis infections in the presence of S. aureus and their effect in Skin Cutaneous Melanoma infections. GEO with accession number (GSE207390) was used to acquire the data. The microarray test was used to perform this investigation. Six sets of keratinocytes, IL-17A, and TNF-&#x3b1; were cultivated together. Several kinds of bioinformatics tools were employed to fulfill the study's objective. Gene hub analysis of 34284 genes was scanned. Six genes demonstrated high expression rates were expressed during the metastatic stage: CCL27, IL19, PAPPA2, UHRF1, IFNAR2, and GLS2. IFNAR2 and UHRF1 had the highest levels of expression. The expression of the COL4A4 gene rose in response to sun exposure, but the expression of the other genes remained same. The existence of cytokine groups with S. aureus in keratinocytes influences the expression difference compared to the other groups. This work adds to our understanding of the molecular alterations that occur in the epidermis of psoriasis patients, as well as their relationship to comorbidities.

Chronic respiratory diseases are an important global issue, particularly in Asia, where burden patterns vary widely across countries. With more than half the world's population living in Asia, understanding the national and regional burden of chronic respiratory diseases is essential; however, research on this area remains inadequate. We aimed to investigate the burden of chronic respiratory diseases in Asia at national and regional levels, and to identify key risk factors. The Global Burden of Diseases, Injuries, and Risk Factors Study 2023 provides estimates for assessing the burden of chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease (ILD), and pulmonary sarcoidosis. We focused on 34 countries in Asia, encompassing the high-income Asia Pacific region and central, east, south, and southeast Asia. Estimates for age-standardised prevalence and disability-adjusted life-year (DALY) rates per 100&#x2009;000 population, including 95% uncertainty intervals (UIs), were extracted by location, sex, year, and Socio-demographic Index (SDI). The average annual percentage change was calculated and presented as a percentage with 95% CIs. Estimates of modifiable attributable risk factors for DALYs and mortality were also included. In Asia, the age-standardised prevalence and DALY rates for chronic respiratory diseases generally declined from 1990 to 2023; however, the trend varied substantially by disease and country. In 2023, the age-standardised prevalence rate of COPD was highest in south Asia (3044&#xb7;18 [95% UI 2748&#xb7;67-3303&#xb7;04] per 100&#x2009;000 population), while the age-standardised asthma prevalence rate was highest in the high-income Asia Pacific region (4870&#xb7;24 [4046&#xb7;70-5962&#xb7;78] per 100&#x2009;000 population) and southeast Asia (4778&#xb7;18 [3970&#xb7;25-5735&#xb7;61] per 100&#x2009;000 population). Despite southeast Asia and the high-income Asia Pacific region having a similar age-standardised asthma prevalence rate, southeast Asia had a higher age-standardised DALY rate (508&#xb7;67 [95% UI 394&#xb7;89-669&#xb7;92] per 100&#x2009;000 population) compared with the high-income Asia Pacific region (204&#xb7;40 [129&#xb7;23-290&#xb7;41] per 100&#x2009;000 population). A decrease in the age-standardised DALY rate for chronic respiratory diseases was observed with increasing SDI, contrasting with its prevalence patterns. Age-standardised DALY rates of COPD decreased in all Asian countries except for Georgia (average annual percentage change 1&#xb7;37 [95% CI 1&#xb7;26-1&#xb7;48]) and Kazakhstan (0&#xb7;73 [0&#xb7;55-0&#xb7;93]), and age-standardised DALY rates of asthma decreased in all countries. Smoking and ambient particulate matter pollution were identified as leading attributable risk factors for chronic respiratory diseases across Asia. Household air pollution from solid fuels was a regionally pronounced risk factor for chronic respiratory diseases, particularly in south Asia (age-standardised DALY rate 657&#xb7;58 [95% UI 485&#xb7;04-880&#xb7;45] per 100&#x2009;000 population). Although smoking was a major risk factor in males, ambient particulate matter pollution and secondhand smoke emerged as important attributable risk factors for chronic respiratory diseases in females. Countries with lower SDI had markedly higher DALY rates, highlighting the need to address socioeconomic and health-care inequities. Household air pollution from solid fuels continues to impose a substantial but preventable burden in south Asia, calling for clean energy adoption and improved ventilation. Gates Foundation.

The regulatory mechanism of calcification mediated by osteoblasts is ambiguous. Previously, we had found a unique cell-surface A7 antigen recognized by an osteoblast-specific monoclonal antibody, which is specifically expressed in osteoblasts in bone tissues and is involved in the regulation of calcification. This study aimed to identify the molecular entity of the A7 antigen, which is a possible regulator of calcification, expressed on the surface of osteoblasts. Immunoprecipitated A7 antigen was analyzed using SDS-PAGE and mass spectrometry followed by Mascot analysis. Gene expression of the candidate molecule was confirmed by quantitative RT-PCR analysis. Calcification was estimated by using Alizarin Red staining of primary osteoblasts obtained from the calvariae of newborn rats. Immunofluorescence detection of osteoblast-specific antigens was performed using cryosections of the ankle joints obtained from rats with adjuvant-induced arthritis. Proteomics analysis of the A7 antigen strongly suggested it as the insulin receptor-related receptor (IRR), which is an alkali-sensor. IRR mRNA expression was confirmed in rat calvaria-derived primary osteoblasts. Immunoprecipitation and immunoblotting analyses further confirmed the A7 antigen as IRR. Calvaria-derived primary osteoblasts briefly exposed to an alkaline environment showed remarkable stimulation of calcification, involving the IRR-mediated activation of extracellular signal-regulated kinases. Furthermore, immunohistochemical analysis of A7 antigen localization at pathological bone destruction sites showed a possible direct contact between active osteoclasts and osteoblasts expressing the A7 antigen, IRR, the alkali-sensor. A unique osteoblasts surface antigen regulating calcification was identified to be an IRR, the alkali-sensor expressed on the surface of osteoblasts. IRR- expressing osteoblasts were localized in contact with active osteoclasts at pathological bone destruction sites. The current study provides basic evidence that could pave the way for the development of novel medicines targeting the IRR to cure pathological bone diseases.