Assessing causality between obstructive sleep apnea with the dyslipidemia and osteoporosis: a Mendelian randomization study.

Purpose: This study aims to assess the causal relationship between Obstructive Sleep Apnea (OSA), dyslipidemia, and osteoporosis using Mendelian Randomization (MR) techniques. Methods: Utilizing a two-sample MR approach, the study examines the causal relationship between dyslipidemia and osteoporosis. Multivariable MR analyses were used to test the independence of the causal association of dyslipidemia with OSA. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on genome-wide significance, independence, and linkage disequilibrium criteria. The data were sourced from publicly available Genome-Wide Association Studies (GWAS) of OSA (n = 375,657) from the FinnGen Consortium, the Global Lipids Genetics Consortium of dyslipidemia (n = 188,577) and the UK Biobank for osteoporosis (n = 456,348). Results: The MR analysis identified a significant positive association between genetically predicted OSA and triglyceride levels (OR: 1.15, 95% CI: 1.04-1.26, p = 0.006) and a negative correlation with high-density lipoprotein cholesterol (HDL-C) (OR: 0.84, 95% CI: 0.77-0.93, p = 0.0003). Conversely, no causal relationship was found between dyslipidemia (total cholesterol, triglycerides, HDL-C, and low-density lipoprotein cholesterol) and OSA or the relationship between OSA and osteoporosis. Conclusion: The study provides evidence of a causal relationship between OSA and dyslipidemia, highlighting the need for targeted prevention and management strategies for OSA to address lipid abnormalities. The absence of a causal link with osteoporosis and in the reverse direction emphasizes the need for further research in this area.

The influencing factors of stigma towards people with mental illness among nursing students: a mixed-method systematic review.

The stigma of nursing students towards people with mental illness (PMI) creates significant barriers to diagnosis, treatment, and recovery for those with PMI. It can also have a significant impact on the future career choices of nursing students in the field of psychiatry. Current research has found various influencing factors, including personal characteristics and educational influences. However, a comprehensive analysis that encompasses all aspects is lacking. The aim of the study was to conduct a convergent mixed-method systematic review to synthesize the influencing factors of the stigma of nursing students towards PMI according to Framework Integrating Normative Influences on Stigma (FINIS) at micro, meso, and macro levels. PubMed, Web of Science, Cochrane Library, EMBASE, CINAHL and PsycINFO were searched from 1990 to 31 December 2023. The reference lists of the included literature were further checked to identify potentially relevant articles. Two authors independently screened all titles, abstracts, and full-text articles and extracted data. Study quality was assessed by two authors using the Mixed Method Appraisal Tool (MMAT). A total of 4865 articles were initially retrieved, and 73 of these articles were included. The results suggested that the stigma towards PMI by nursing students was influenced by micro, meso and macro levels. At each FINIS level, the most frequent influencing factors are personal characteristics, the treatment system and media images. Numerous interconnected factors exert an influence on the stigma towards PMI among nursing students. Our research can be used to identify barriers and facilitators to nursing students' stigma towards PMI and to provide supporting information for interventions designed to reduce this stigma.

Practical synthesis of chenodeoxycholic acid from phocaecholic acid.

In this study, we developed an effective method for the large-scale synthesis of chenodeoxycholic acid (CDCA) from phocaecholic acid (PhCA). A high total yield of up to 72 % was obtained via five steps including methyl esterification, Ts-protection, bromination, reduction, and hydrolysis. The structures of the intermediates were confirmed by 1H NMR (Nuclear Magnetic Resonance), 13C NMR, HRMS (High Resolution Mass Spectrometry), and IR (Infrared Spectroscopy) spectroscopies. This method offers a new and practical approach to the synthesizing of CDCA.

Directly training temporal Spiking Neural Network with sparse surrogate gradient.

Brain-inspired Spiking Neural Networks (SNNs) have attracted much attention due to their event-based computing and energy-efficient features. However, the spiking all-or-none nature has prevented direct training of SNNs for various applications. The surrogate gradient (SG) algorithm has recently enabled spiking neural networks to shine in neuromorphic hardware. However, introducing surrogate gradients has caused SNNs to lose their original sparsity, thus leading to the potential performance loss. In this paper, we first analyze the current problem of direct training using SGs and then propose Masked Surrogate Gradients (MSGs) to balance the effectiveness of training and the sparseness of the gradient, thereby improving the generalization ability of SNNs. Moreover, we introduce a temporally weighted output (TWO) method to decode the network output, reinforcing the importance of correct timesteps. Extensive experiments on diverse network structures and datasets show that training with MSG and TWO surpasses the SOTA technique.

KLF4 Suppresses the Progression of Hepatocellular Carcinoma by Reducing Tumor ATP Synthesis through Targeting the Mir-206/RICTOR Axis.

To address the increased energy demand, tumor cells undergo metabolic reprogramming, including oxidative phosphorylation (OXPHOS) and aerobic glycolysis. This study investigates the role of Kruppel-like factor 4 (KLF4), a transcription factor, as a tumor suppressor in hepatocellular carcinoma (HCC) by regulating ATP synthesis. Immunohistochemistry was performed to assess KLF4 expression in HCC tissues. Functional assays, such as CCK-8, EdU, and colony formation, as well as in vivo assays, including subcutaneous tumor formation and liver orthotopic xenograft mouse models, were conducted to determine the impact of KLF4 on HCC proliferation. Luciferase reporter assay and chromatin immunoprecipitation assay were utilized to evaluate the interaction between KLF4, miR-206, and RICTOR. The findings reveal low KLF4 expression in HCC, which is associated with poor prognosis. Both in vitro and in vivo functional assays demonstrate that KLF4 inhibits HCC cell proliferation. Mechanistically, it was demonstrated that KLF4 reduces ATP synthesis in HCC by suppressing the expression of RICTOR, a core component of mTORC2. This suppression promotes glutaminolysis to replenish the TCA cycle and increase ATP levels, facilitated by the promotion of miR-206 transcription. In conclusion, this study enhances the understanding of KLF4's role in HCC ATP synthesis and suggests that targeting the KLF4/miR-206/RICTOR axis could be a promising therapeutic approach for anti-HCC therapeutics.

Nalbuphine in Pediatric Emergence Agitation Following Cochlear Implantation: A Randomized Trial.

Background: To investigate the effects of nalbuphine on emergency agitation (EA), which affects up to 80% of the children following otolaryngology procedures, in children undergoing cochlear implantation. Methods: A prospective double-blinded randomized controlled clinical trial was conducted between November 2020 and October 2022. Eligible children, aged 6 months to 3 years old, were randomly assigned to either 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg nalbuphine or 0.9% saline groups. EA was defined by the Pediatric Anesthesia Emergence Delirium (PAED) score ≥10. Extubation time, post-anesthesia care unit (PACU) length of stay, severe EA (PAED ≥ 15), peak PAED score, the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale, Ramsay sedation score, and adverse events were also recorded. Results: A total of 104 children were enrolled, with 26 children in each group. Nalbuphine significantly reduced the EA occurrence from 73.1% in the saline group to 38.5%, 30.8%, and 26.9% in the 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg nalbuphine groups, respectively (P < 0.001), without affecting the extubation time and PACU length of stay. More children (34.6%) in the 0.9% saline group experienced severe EA. Higher dose nalbuphine (0.15 mg/kg, 0.2 mg/kg) showed lower peak PAED score, better analgesia and sedation effect compared with 0.1 mg/kg nalbuphine and saline groups. However, 0.2mg/kg nalbuphine caused undesired over-sedation in two (7.7%) children. No other adverse events were reported. Conclusion: Young children undergoing cochlear implantation surgery were at a high risk of EA and postoperative pain, while 0.2 mg/kg nalbuphine might be an ideal candidate for EA and pain prevention when used under close monitoring. Trial Registration: ChiCTR2000040407.

Machine learning enables pan-cancer identification of mutational hotspots at persistent CTCF binding sites.

CCCTC-binding factor (CTCF) is an insulator protein that binds to a highly conserved DNA motif and facilitates regulation of three-dimensional (3D) nuclear architecture and transcription. CTCF binding sites (CTCF-BSs) reside in non-coding DNA and are frequently mutated in cancer. Our previous study identified a small subclass of CTCF-BSs that are resistant to CTCF knock down, termed persistent CTCF binding sites (P-CTCF-BSs). P-CTCF-BSs show high binding conservation and potentially regulate cell-type constitutive 3D chromatin architecture. Here, using ICGC sequencing data we made the striking observation that P-CTCF-BSs display a highly elevated mutation rate in breast and prostate cancer when compared to all CTCF-BSs. To address whether P-CTCF-BS mutations are also enriched in other cell-types, we developed CTCF-INSITE-a tool utilising machine learning to predict persistence based on genetic and epigenetic features of experimentally-determined P-CTCF-BSs. Notably, predicted P-CTCF-BSs also show a significantly elevated mutational burden in all 12 cancer-types tested. Enrichment was even stronger for P-CTCF-BS mutations with predicted functional impact to CTCF binding and chromatin looping. Using in vitro binding assays we validated that P-CTCF-BS cancer mutations, predicted to be disruptive, indeed reduced CTCF binding. Together this study reveals a new subclass of cancer specific CTCF-BS DNA mutations and provides insights into their importance in genome organization in a pan-cancer setting.

Nano-enabled strategies to promote safe crop production in heavy metal(loid)-contaminated soil.

Nanobiotechnology is a potentially safe and sustainable strategy for both agricultural production and soil remediation, yet the potential of nanomaterials (NMs) application to remediate heavy metal(loid)-contaminated soils is still unclear. A meta-analysis with approximately 6000 observations was conducted to quantify the effects of NMs on safe crop production in soils contaminated with heavy metal(loid) (HM), and a machine learning approach was used to identify the major contributing features. Applying NMs can elevate the crop shoot (18.2 %, 15.4-21.2 %) and grain biomass (30.7 %, 26.9-34.9 %), and decrease the shoot and grain HM concentration by 31.8 % (28.9-34.5 %) and 46.8 % (43.7-49.8 %), respectively. Iron-NMs showed a greater potential to inhibit crop HM uptake compared to other types of NMs. Our result further demonstrates that NMs application substantially reduces the potential health risk of HM in crop grains by human health risk assessment. The NMs-induced reduction in HM accumulation was associated with decreasing HM bioavailability, as well as increased soil pH and organic matter. A random forest model demonstrates that soil pH and total HM concentration are the two significant features affecting shoot HM accumulation. This analysis of the literature highlights the significant potential of NMs application in promoting safe agricultural production in HM-contaminated agricultural lands.

Urban health advantage and penalty in aging populations: a comparative study across major megacities in China.

Background: Urban living is linked to better health outcomes due to a combination of enhanced access to healthcare, transportation, and human development opportunities. However, spatial inequalities lead to disparities, resulting in urban health advantages and penalties. Understanding the relationship between health and urban development is needed to generate empirical evidence in promoting healthy aging populations. This study provides a comparative analysis using epidemiological evidence across diverse major Chinese cities, examining how their unique urban development trajectories over time have impacted the health of their aging residents. Methods: We tracked changes in air pollution (NO2, PM2.5, O3), green space (measured by NDVI), road infrastructure (ring road areas), and nighttime lighting over 20 years in six major cities in China. We followed a longitudinal cohort of 4992 elderly participants (average age 87.8 years) over 16,824 person-years. We employed Cox proportional hazard regression to assess longevity, assessing 14 variables, including age, sex, ethnicity, marital status, residence, household income, occupation, education, smoking, alcohol consumption, exercise, and points of interest (POI) count of medicine-related facilities, sports, and leisure service-related places, and scenic spots within a 5 km-radius buffer. Findings: Geographic proximity to points of interest significantly improves survival. Elderly living in proximity of the POI-rich areas had a 34.6%-35.6% lower mortality risk compared to those in POI-poor areas, for the highest compared to the lowest quartile. However, POI-rich areas had higher air pollution levels, including PM2.5 and NO2, which was associated with a 21% and 10% increase in mortality risk for increase of 10 µg/m3, respectively. The benefits of urban living had higher effect estimates in monocentric cities, with clearly defined central areas, compared to polycentric layouts, with multiple satellite city centers. Interpretation: Spatial inequalities create urban health advantages for some and penalties for others. Proximity to public facilities and economic activities is associated with health benefits, and may counterbalance the negative health impacts of lower green space and higher air pollution. Our empirical evidence show optimal health gains for age-friendly urban environments come from a balance of infrastructure, points of interest, green spaces, and low air pollution. Funding: Natural Science Foundation of Beijing (IS23105), National Natural Science Foundation of China (82250610230, 72061137004), World Health Organization (2024/1463606-0), Research Fund Vanke School of Public Health Tsinghua University (2024JC002), Beijing TaiKang YiCai Public Welfare Foundation, National Key R&D Program of China (2018YFC2000400).

Effects of walking on epigenetic age acceleration: a Mendelian randomization study.

INTRODUCTION: Walking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA). METHODS: We conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy. RESULTS: The IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = - 1.84, 95% CI (- 2.94, - 0.75)), PhenoAge (BETA = - 1.57, 95% CI (- 3.05, - 0.08)), Horvath (BETA = - 1.09 (- 2.14, - 0.04)), and Hannum (BETA = - 1.63, 95% CI (- 2.70, - 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05). CONCLUSION: Our evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.

Nanopore-based targeted next-generation sequencing of tissue samples for tuberculosis diagnosis.

Objective: Diagnosing tuberculosis (TB) can be particularly challenging in the absence of sputum for pulmonary tuberculosis cases and extrapulmonary TB (EPTB). This study evaluated the utility of nanopore-based targeted next-generation sequencing (tNGS) for diagnosing TB in tissue samples, and compared its efficacy with other established diagnostic methods. Methods: A total of 110 tissue samples from clinical cases were examined. The sensitivity and specificity of tNGS were benchmarked against a range of existing diagnostic approaches including hematoxylin and eosin (HE) staining in conjunction with acid-fast bacilli (AFB) detection, HE staining combined with PCR, HE staining paired with immunohistochemistry (IHC) using anti-MPT64, and the Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) assay. Results: The sensitivity and specificity of tNGS were 88.2 and 94.1%, respectively. The respective sensitivities for HE staining combined with AFB, HE staining combined with PCR, HE staining combined with IHC using anti-MPT64, and Xpert MTB/RIF were 30.1, 49.5, 47.3, and 59.1%. The specificities for these methods were 82.4, 88.2, 94.1, and 94.1%, respectively. Analysis of drug resistance based on tNGS results indicated that 10 of 93 TB patients (10.75%) had potential drug resistance. Conclusion: Targeted next-generation sequencing achieved higher accuracy than other established diagnostic methods, and can play a crucial role in the rapid and accurate diagnosis of TB, including drug-resistant TB.

Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds.

One question in lymphocyte homing is how integrins are rapidly activated to enable immediate arrest of fast rolling lymphocytes upon encountering chemokines at target vascular beds given the slow chemokine-induced integrin inside-out activation. Herein we demonstrate that chemokine CCL25-triggered Ca2+ influx induces T cell membrane-proximal external Ca2+ concentration ([Ca2+]ex) drop in 6 s from physiological concentration 1.2 mM to 0.3 mM, a critical extracellular Ca2+ threshold for inducing αLß2 activation, triggering rapid αLß2 activation and T cell arrest before occurrence of αLß2 inside-out activation. Talin knockdown inhibits the slow inside-out activation of αLß2 but not [Ca2+]ex drop-triggered αLß2 quick activation. Blocking Ca2+ influx significantly suppresses T cell rolling-to-arrest transition and homing to skin lesions in a mouse psoriasis model, thus alleviating skin inflammation. [Ca2+]ex decrease-triggered rapid integrin activation bridges the gap between initial chemokine stimulation and slow integrin inside-out activation, ensuring immediate lymphocyte arrest and subsequent diapedesis on the right location.

Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes.

In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes.

The significance of CD8+ tumor-infiltrating lymphocytes exhaustion heterogeneity and its underlying mechanism in diffuse large B-cell lymphoma.

CD8+ tumor-infiltrating lymphocytes (TILs) exhaustion is a major barrier to effective tumor control in diffuse large B-cell lymphoma (DLBCL) and may consist of heterogeneous populations with different functional states. We profiled the CD8+TILs exhaustion heterogeneity and explored its clinical significance as well as the underlying mechanism through single-cell RNA sequencing (n = 7), bulk RNA sequencing (n = 3300), immunohistochemistry (n = 116), and reverse transcription-quantitative polymerase chain reaction (n = 95), and somatic mutation data (n = 48). Our results demonstrated that exhausted CD8+TILs in DLBCL were composed of progenitor and terminal states characterized by CCL5 and TUBA1B, respectively. High terminally exhausted CD8+TILs indicated an immunosuppressive tumor microenvironment, activated B-cell-like subtype, inferior prognosis, and poor response to immune checkpoint blockade therapy in DLBCL. Our study further demonstrated that the CD39/A2AR-related signaling may be the potential pathway that promoted the transition of progenitor toward terminally exhausted CD8+TILs in DLBCL. Furthermore, the CD39/A2AR-related pathway in DLBCL may be regulated by BATF and STAT3 in exhausted CD8+TILs, and MYD88 mutation in tumor cells. Our study highlights CD8+TILs exhaustion heterogeneity and its possible regulatory mechanism provides a novel prognostic indicator and can facilitate the optimization of individualized immunotherapy.

Itaconate and dimethyl itaconate upregulate IL-6 production in the LPS-induced inflammation in mice.

Itaconate is one of the most studied immunometabolites produced by myeloid cells during inflammatory response. It mediates a wide range of anti-inflammatory and immunoregulatory effects and plays a role in a number of pathological states, including autoimmunity and cancer. Itaconate and its derivatives are considered as potential therapeutic agents for treatment of inflammatory diseases. While immunoregulatory effects of itaconate have been extensively studied in vitro and using knock-out mouse models, less is known about how therapeutic administration of this metabolite regulates inflammatory response in vivo. Here, we investigate the immunoregulatory properties of exogenous administration of itaconate (ITA) and its derivative dimethyl itaconate (DI) in a mouse model of LPS-induced inflammation. The data show that administration of ITA or DI controls systemic production of multiple cytokines, including increased IL-10 production. However, only DI was able to suppress systemic production of IFNγ and IL-1ß. In contrast to in vitro data, administration of ITA or DI in vivo resulted in systemic upregulation of IL-6 in the blood. Electrophilic stress due to ITA or DI was not responsible for IL-6 upregulation. However, inhibition of SDH with dimethyl malonate (DM) also resulted in elevated systemic levels of IL-6 and IL-10. Taken together, our study reports a novel effect of exogenous itaconate and its derivative DI on the production of IL-6 in vivo, with important implications for the development of itaconate-based anti-inflammatory therapies.

Exogenous selenium promotes cadmium reduction and selenium enrichment in rice: Evidence, mechanisms, and perspectives.

Cadmium (Cd) accumulation in rice, a global environmental issue, poses a significant threat to human health due to its widespread presence and potential transfer through the food chain. Selenium (Se), an essential micronutrient for humans and plants, can reduce Cd uptake in rice and alleviate Cd-induced toxicity. However, the effects and mechanisms of Se supplementation on rice performance in Cd-contaminated soil remain largely unknown. Here, a global meta-analysis was conducted to evaluate the existing knowledge on the effects and mechanisms by which Se supplementation impacts rice growth and Cd accumulation. The result showed that Se supplementation has a significant positive impact on rice growth in Cd-contaminated soil. Specifically, Se supplementation decreased Cd accumulation in rice roots by 16.3 % (11.8-20.6 %), shoots by 24.6 % (19.9-29.1 %), and grain by 37.3 % (33.4-40.9 %), respectively. The grain Cd reduction was associated with Se dose and soil Cd contamination level but not Se type or application method. Se influences Cd accumulation in rice by regulating the expression of Cd transporter genes (OSLCT1, OSHMA2, and OSHMA3), enhancing Cd sequestration in the cell walls, and reducing Cd bioavailability in the soil. Importantly, Se treatment promoted Se enrichment in rice and alleviated oxidative damage associated with Cd exposure by stimulating photosynthesis and activating antioxidant enzymes. Overall, Se treatment mitigated the health hazard associated with Cd in rice grains, particularly in lightly contaminated soil. These findings reveal that Se supplementation is a promising strategy for simultaneous Cd reduction and Se enrichment in rice.

Excess deaths and loss of life expectancy attributed to long-term NO2 exposure in the Chinese elderly.

BACKGROUND: Evidence linking nitrogen dioxide (NO2) air pollution to life span of high-vulnerability older adults is extensively scarce in low- and middle-income countries. This study seeks to quantify mortality risk, excess deaths, and loss of life expectancy (LLE) associated with long-term exposure to NO2 among elderly individuals in China. METHODS: A nationwide dynamic cohort of 20352 respondents ≥65 years old were enrolled from the China Longitudinal Health and Longevity Survey during 2005-2018. Residential exposures to NO2 and co-pollutants were assessed by well-validated spatiotemporal prediction models. A Cox regression model with time-dependent covariates was utilized to quantify the association of all-cause mortality with NO2 exposure, controlling for confounders such as demographics, lifestyle, health status, and ambient temperature. NO2-attributable deaths and LLE were evaluated for the years 2010 and 2020 based on the pooled NO2-mortality relation derived from multi-national cohort investigations. Decomposition analyses were conducted to dissociate net shift in NO2-related deaths between 2010 and 2020 into four primary contributing factors. RESULTS: A total of 14313 deaths were recorded during follow-up of approximately 100 hundred person-years (median 3.6 years). We observed an approximately linear relationship (nonlinear P = 0.882) of NO2 exposure with all-cause death across a broad range from 6.6 to 95.7 µg/m3. Every 10-µg/m3 rise in yearly average NO2 concentration was linked to a hazard ratio (HR) of 1.045 (95% confidence interval [CI]: 1.031-1.059). In the updated meta-analysis of this study and 9 existing cohorts, we estimated a pooled HR of 1.043 (95% CI: 1.023-1.063) for each 10-µg/m3 growth in NO2. Reaching a 10-µg/m3 counterfactual target of NO2 concentration in China could avoid 0.33 (95% empirical CI: 0.19-0.49) million premature deaths and an LLE of 0.40 (95% empirical CI: 0.23-0.59) years in 2010, which greatly dropped to 0.24 (95% empirical CI: 0.14-0.36) million deaths and 0.21 (95% empirical CI: 0.12-0.31) years of LLE in 2020. The net fall in NO2-attributable deaths (-26.8%) between 2010 and 2020 was primarily driven by the declines in both NO2 concentration (-41.6%) and mortality rate (-27.1%) under population growth (+41.0%) and age structure transition (+0.9%). CONCLUSIONS: Our findings provide national evidence for increased risk of premature death and loss of life expectancy attributed to later-life NO2 exposure among the elderly in China. In an accelerated aging society, strengthened clean air actions should be formulated to minimize the health burden and regional inequality in NO2-attributable mortality.

The Etiology of Rapidly Progressive Dementia: A 3-Year Retrospective Study in a Tertiary Hospital in China.

Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation.

Wavelength-Dependent Activity of Oxygen Species in Propane Conversion on Rutile TiO2(110).

Photocatalytic oxidative dehydrogenation of propane (C3H8) into propene (C3H6) under mild conditions holds great potential in the chemical industry, but understanding how active species participate in C3H8 conversion remains a significant challenge. Here, the wavelength-dependent activities of bridging oxygen (Ob2-) and the Ti5c-bound oxygen adatom (OTi2-) of model rutile (R) TiO2(110) in C3H8 conversion have been investigated. Under 257 and 343 nm irradiation, hole-trapped OTi- and Ob- can abstract the hydrogen atom of C3H8, forming the CH3CH•CH3 radical and C3H6. However, the rate of C3H8 conversion with hole-trapped Ob- is strongly dependent on the wavelength, primarily producing the C3H7• radical. In the case of hole-trapped OTi-, C3H6 is the main product, which is nearly independent of wavelength. The differences in the wavelength-dependent activity and product selectivity are likely due to dynamic control rather than thermodynamic control. The result provides a deeper understanding of the dynamic processes involved in the conversion of light alkanes in TiO2 photocatalysis.