Hydrate Technologies for CO2 Capture and Sequestration: Status and Perspectives.

CO2 capture and sequestration based on hydrate technology are considered supplementary approaches for reducing carbon emissions and mitigating the greenhouse effect. Direct CO2 hydrate formation and CH4 gas substitution in natural gas hydrates are two of the main methods used for the sequestration of CO2 in hydrates. In this Review, we introduce the crystal structures of CO2 hydrates and CO2-mixed gas hydrates and summarize the interactions between the CO2 molecules and clathrate hydrate/H2O frames. In particular, we focus on the role of diffraction techniques in analyzing hydrate structures. The kinetic and thermodynamic properties then are introduced from micro/macro perspectives. Furthermore, the replacement of natural gas with CO2/CO2-mixed gas is discussed comprehensively in terms of intermolecular interactions, influencing factors, and displacement efficiency. Based on the analysis of related costs, risks, and policies, the economics of CO2 capture and sequestration based on hydrate technology are explained. Moreover, the difficulties and challenges at this stage and the directions for future research are described. Finally, we investigate the status of recent research related to CO2 capture and sequestration based on hydrate technology, revealing its importance in carbon emission reduction.

Monitoring protein conformational changes using fluorescent nanoantennas.

Understanding the relationship between protein structural dynamics and function is crucial for both basic research and biotechnology. However, methods for studying the fast dynamics of structural changes are limited. Here, we introduce fluorescent nanoantennas as a spectroscopic technique to sense and report protein conformational changes through noncovalent dye-protein interactions. Using experiments and molecular simulations, we detect and characterize five distinct conformational states of intestinal alkaline phosphatase, including the transient enzyme-substrate complex. We also explored the universality of the nanoantenna strategy with another model protein, Protein G and its interaction with antibodies, and demonstrated a rapid screening strategy to identify efficient nanoantennas. These versatile nanoantennas can be used with diverse dyes to monitor small and large conformational changes, suggesting that they could be used to characterize diverse protein movements or in high-throughput screening applications.

ALKBH5 regulates chicken adipogenesis by mediating LCAT mRNA stability depending on m6A modification.

BACKGROUND: Previous studies have demonstrated the role of N6-methyladenosine (m6A) RNA methylation in various biological processes, our research is the first to elucidate its specific impact on LCAT mRNA stability and adipogenesis in poultry. RESULTS: The 6 100-day-old female chickens were categorized into high (n = 3) and low-fat chickens (n = 3) based on their abdominal fat ratios, and their abdominal fat tissues were processed for MeRIP-seq and RNA-seq. An integrated analysis of MeRIP-seq and RNA-seq omics data revealed 16 differentially expressed genes associated with to differential m6A modifications. Among them, ELOVL fatty acid elongase 2 (ELOVL2), pyruvate dehydrogenase kinase 4 (PDK4), fatty acid binding protein 9 (PMP2), fatty acid binding protein 1 (FABP1), lysosomal associated membrane protein 3 (LAMP3), lecithin-cholesterol acyltransferase (LCAT) and solute carrier family 2 member 1 (SLC2A1) have ever been reported to be associated with adipogenesis. Interestingly, LCAT was down-regulated and expressed along with decreased levels of mRNA methylation methylation in the low-fat group. Mechanistically, the highly expressed ALKBH5 gene regulates LCAT RNA demethylation and affects LCAT mRNA stability. In addition, LCAT inhibits preadipocyte proliferation and promotes preadipocyte differentiation, and plays a key role in adipogenesis. CONCLUSIONS: In conclusion, ALKBH5 mediates RNA stability of LCAT through demethylation and affects chicken adipogenesis. This study provides a theoretical basis for further understanding of RNA methylation regulation in chicken adipogenesis.

Genetic landscape of human mitochondrial genome using whole-genome sequencing.

Increasing evidences suggest that mitochondrial dysfunction is implicated in diseases and aging, and whole-genome sequencing (WGS) is the most unbiased method in analyzing the mitochondrial genome (mtDNA). However, the genetic landscape of mtDNA in the Chinese population has not been fully examined. Here, we described the genetic landscape of mtDNA using WGS data from Chinese individuals (n = 3241). We identified 3892 mtDNA variants, of which 3349 (86%) were rare variants. Interestingly, we observed a trend toward extreme heterogeneity of mtDNA variants. Our study observed a distinct purifying selection on mtDNA, which inhibits the accumulation of harmful heteroplasmies at the individual level: (1) mitochondrial dN/dS ratios were much <1; (2) the dN/dS ratio of heteroplasmies was higher than homoplasmies; (3) heteroplasmies had more indels and predicted deleterious variants than homoplasmies. Furthermore, we found that haplogroup M (20.27%) and D (20.15%) had the highest frequencies in the Chinese population, followed by B (18.51%) and F (16.45%). The number of variants per individual differed across haplogroup groups, with a higher number of homoplasmies for the M lineage. Meanwhile, mtDNA copy number was negatively correlated with age but positively correlated with the female sex. Finally, we developed an mtDNA variation database of Chinese populations called MTCards (http://genemed.tech/mtcards/) to facilitate the query of mtDNA variants in this study. In summary, these findings contribute to different aspects of understanding mtDNA, providing a better understanding of the genetic basis of mitochondrial-related diseases.

Plexin D1 negatively regulates macrophage-derived foam cell migration via the focal adhesion kinase/Paxillin pathway.

BACKGROUND: Macrophage-derived foam cell formation is a hallmark of atherosclerosis and is retained during plaque formation. Strategies to inhibit the accumulation of these cells hold promise as viable options for treating atherosclerosis. Plexin D1 (PLXND1), a member of the Plexin family, has elevated expression in atherosclerotic plaques and correlates with cell migration; however, its role in macrophages remains unclear. We hypothesize that the guidance receptor PLXND1 negatively regulating macrophage mobility to promote the progression of atherosclerosis. METHODS: We utilized a mouse model of atherosclerosis based on a high-fat diet and an ox-LDL- induced foam cell model to assess PLXND1 levels and their impact on cell migration. Through western blotting, Transwell assays, and immunofluorescence staining, we explored the potential mechanism by which PLXND1 mediates foam cell motility in atherosclerosis. RESULTS: Our study identifies a critical role for PLXND1 in atherosclerosis plaques and in a low-migration capacity foam cell model induced by ox-LDL. In the aortic sinus plaques of ApoE-/- mice, immunofluorescence staining revealed significant upregulation of PLXND1 and Sema3E, with colocalization in macrophages. In macrophages treated with ox-LDL, increased expression of PLXND1 led to reduced pseudopodia formation and decreased migratory capacity. PLXND1 is involved in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK. Additionally, FAK inhibitors counteract the ox-LDL-induced migration suppression by modulating the phosphorylation states of FAK, Paxillin and their downstream effectors CDC42 and PAK. CONCLUSION: Our findings indicate that PLXND1 plays a role in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK to promoting atherosclerosis.

Adaptative responses of Neurospora crassa by histidine kinases upon the attack of the arthropod Sinella curviseta.

Histidine kinases (HKs) are important sensor proteins in fungi and play an essential role in environmental adaptation. However, the mechanisms by which fungi sense and respond to fungivores attack via HKs are not fully understood. In this study, we utilized Neurospora crassa to investigate the involvement of HKs in responding to fungivores attack. We found that the 11 HKs in N. crassa not only affected the growth and development, but also led to fluctuations in antioxidant production. Ten mutants in the genes encoding HKs (except ∆phy1) showed increased production of reactive oxygen species (ROS), especially upon Sinella curviseta attack. The ROS burst triggered changes in conidia and perithecial beaks formation, as well as accumulation of ß-glucan, ergothioneine, ergosterol, and carotenoids. ß-glucan was increased in ∆hk9, ∆os1, ∆hcp1, ∆nik2, ∆sln1, ∆phy1 and ∆phy2 mutants compared to the wild-type strain. In parallel, ergothioneine accumulation was improved in ∆phy1 and ∆hk16 mutants and further increased upon attack, except in ∆os1 and ∆hk16 mutants. Additionally, fungivores attack stimulated ergosterol and dehydroergosterol production in ∆hk9 and ∆os1 mutants. Furthermore, deletion of these genes altered carotenoid accumulation, with wild-type strain, ∆hk9, ∆os1, ∆hcp1, ∆sln1, ∆phy2, and ∆dcc1mutants showing an increase in carotenoids upon attack. Taken together, HKs are involved in regulating the production of conidia and antioxidants. Thus, HKs may act as sensors of fungivores attack and effectively improve the adaptive capacity of fungi to environmental stimuli.

Metabolic obesity phenotypes and all-cause mortality among the Chinese oldest-old population: a prospective cohort study.

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

TransFlow: a Snakemake workflow for transmission analysis of Mycobacterium tuberculosis whole-genome sequencing data.

MOTIVATION: Whole-genome sequencing (WGS) is increasingly used to aid the understanding of Mycobacterium tuberculosis (MTB) transmission. The epidemiological analysis of tuberculosis based on the WGS technique requires a diverse collection of bioinformatics tools. Effectively using these analysis tools in a scalable and reproducible way can be challenging, especially for non-experts. RESULTS: Here, we present TransFlow (Transmission Workflow), a user-friendly, fast, efficient and comprehensive WGS-based transmission analysis pipeline. TransFlow combines some state-of-the-art tools to take transmission analysis from raw sequencing data, through quality control, sequence alignment and variant calling, into downstream transmission clustering, transmission network reconstruction and transmission risk factor inference, together with summary statistics and data visualization in a summary report. TransFlow relies on Snakemake and Conda to resolve dependencies among consecutive processing steps and can be easily adapted to any computation environment. AVAILABILITY AND IMPLEMENTATION: TransFlow is free available at https://github.com/cvn001/transflow. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association between atherogenic index of plasma and all-cause mortality and specific-mortality: a nationwide population­based cohort study.

BACKGROUND: Atherogenic index of plasma (AIP), a marker of atherosclerosis and cardiovascular disease (CVD). However, few studies have investigated association between AIP and all-cause mortality and specific-mortality in the general population. METHODS: This study included data from 14,063 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included all-cause mortality and specific-mortality. Survey-weighted cox regressions were performed to evaluate the relation between AIP and all-cause mortality and specific-mortality. Weighted restricted cubic spline was conducted to examin the non-linear relationship. RESULTS: During 10 years of follow-up, we documented 2,077, 262, 854, and 476 cases of all-cause mortality, diabetes mortality, CVD mortality and cancer mortality, respectively. After adjustment for potential confounders, we found that atherogenic index of plasma (AIP) was significantly associated with an increased risk of diabetes mortality when comparing the highest to the lowest quantile of AIP in female (p for trend = 0.001) or participants older than 65 years (p for trend = 0.002). AIP was not significantly associated with all-cause mortality, CVD mortality and cancer mortality (p > 0.05). Moreover, a non-linear association was observed between AIP and all-cause mortality in a U-shape (p for non-linear = 0.0011), while a linear relationship was observed with diabetes mortality and non-diabetes mortality (p for linear < 0.0001). CONCLUSIONS: In this study, there is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. Besides, a higher AIP was significantly associated with an increased risk of diabetes mortality, which only found in women older than 65 years. AIP was associated with all-cause mortality in a U-shape. This association could be explained by the finding that higher AIP predicted a higher risk of death from diabetes, and that lower AIP predicted a higher risk of death from non-diabetes causes.

We used a large national database and a prospective cohort study with a long follow-up period. Higher AIP was significantly associated with an increased risk of diabetes mortality, only in women older than 65 years. There is a no significant association between high AIP levels and a high risk of all-cause and cardiovascular mortality. AIP was associated with all-cause mortality in a U-shape. This finding suggest that controlling AIP levels may have a positive effect on reducing diabetes mortality.

Central (Aortic) Cannulation versus Peripheral (Axillary or Femoral) Cannulation in Acute Type A Aortic Dissections: A Meta-Analysis of Comparative Studies.

Background: There has been an increased interest in using antegrade cannulation techniques during surgery for type A aortic dissection. While the utilization of central artery cannulation has been on the rise in recent times, its effectiveness and safety still require thorough examination. This study aimed to explore both the efficiency and safety of central arterial cannulation. Methods: A meta-analysis was conducted on studies that evaluated surgical outcomes when using central artery cannulation (CAC) in comparison to axillary artery cannulation (AXC) or femoral artery cannulation (FAC). Results: 10 retrospective observational studies were included, enrolling 3022 patients (CAC = 1208 vs. FAC = 606; CAC = 1051 vs. AXC = 1119). Among these, 4 articles involved axillary artery cannulation, femoral artery cannulation, and central artery cannulation. Central cannulation was linked to decreased short-term mortality [odds ratio, 0.66, 95% confidence interval (CI) (0.48, 0.89), χ 2 = 3.27, p = 0.007; I 2 = 0; p = 0.86] compared to femoral cannulation. Additionally, central cannulation was associated with a lower occurrence of temporary neurological dysfunction (TND) [odds ratio, 0.57, 95% CI (0.38, 0.85), χ 2 = 0.88, p = 0.006; I 2 = 0%, p = 0.83] when compared with femoral cannulation. However, there was no statistical significance in mortality and TND between the central cannulation and axillary cannulation groups. Conclusions: This meta-analysis reveals that central cannulation surpasses femoral cannulation in lowering short-term mortality and the occurrence of TND among patients undergoing surgery for type A acute aortic dissection. However, central cannulation does not exhibit a higher mortality and TND compared to axillary cannulation.

Lnc-PSMA8-1 activated by GEFT promotes rhabdomyosarcoma progression via upregulation of mTOR expression by sponging miR-144-3p.

BACKGROUND: GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS. METHODS: GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT-PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT-PCR analysis, Western blot analysis, and cell functional experiments. RESULTS: The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA-miRNA-mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression. CONCLUSION: Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.

Piracetam reduces oxidative stress and mitochondrial function impairment in an in vitro model of vascular dementia.

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.

Surgical Treatment for Type A Aortic Dissection after Endovascular Aortic Repair: A 12-year, Single-Center Study.

OBJECTIVE: This study aims to investigate the clinical manifestations, operative techniques, and outcomes of patients who undergo open repair after thoracic endovascular aortic repair (TEVAR). METHODS: From January 2010 to June 2022, 113 consecutive type A aortic dissection (TAAD) patients underwent secondary open operation after TEVAR at our institution, and the median interval from primary intervention to open surgery was 12 (1.9-48.0) months. We divided the patients into two groups (RTAD (retrograde type A dissection) group, N = 56; PNAD (proximal new aortic dissection) group, N = 57) according to their anatomical features. Survival analysis during the follow-up was evaluated using a Kaplan-Meier survival curve and a log-rank test. RESULTS: The 30-day mortality was 6.2% (7/113), the median follow-up period was 31.7 (IQR 14.7-65.6) months, and the overall survival at 1 year, 5 years, and 10 years was 88.5%, 88.5%, and 87.6%, respectively. Fourteen deaths occurred during the follow-up, but there were no late aorta-related deaths. Three patients underwent total thoracoabdominal aortic replacement 1 year after a second open operation. The RTAD group had a smaller ascending aorta size (42.5 ± 7.7 mm vs 48.4 ± 11.4 mm; P < .01) and a closer proximal landing zone (P < .01) compared to the PNAD group. However, there were no differences in survival between the two groups. CONCLUSIONS: TAAD can present as an early or a late complication after TEVAR due to stent-grafting-related issues or disease progression. Open operation can be performed to treat TAAD, and this has acceptable early and mid-term outcomes. Follow-up should become mandatory for patients after TEVAR because these patients are at increased risk for TAAD.

Downregulation of miR-455-3p in decidual cells promotes macrophage polarization and suppresses trophoblasts invasion.

Preeclampsia (PE) is a common complication of pregnancy, usually accompanied by symptoms such as hypertension and proteinuria. It can induce severe conditions that may result in maternal and fetal morbidity and fatality. In this study, we use bioinformatics analysis to compare microRNA microassay in decidual stromal cells from PE patients and healthy donors. Our result indicated that placentas from PE patients had a higher CCL1/CXCL2 expression, compared with those from healthy donors. Bioinformatics analysis confirmed that decidual stromal cells derived from PE patients expressed significantly lower miR-455-3p than those derived from healthy donors. Transfection of miR-455-3p inhibitors enhanced the CCL2/CXCL8 expression in decidual stromal cells, and luciferase activity assay confirmed that nuclear factor of activated T cells 5 (NFAT5) mRNA was the direct target of miR-455-3p; NFAT5 also promoted cytokine secretion. In the flow cytometry study, higher M1 macrophage infiltration was observed in placentas from PE patients than in those from healthy donors. We also observed that condition medium (CM) derived from decidual stromal cells could significantly promote M1 polarization of macrophages after transfection with miR-455-3p inhibitor; further, transwell invasion assay confirmed that decidual stromal cells-CM educated macrophages suppressed trophoblast invasion. Taken together, our result demonstrates that downregulation of miR-455-3p in decidual stromal cells can promote macrophage polarization and suppress trophoblasts invasion.

Association between dietary diversity changes and frailty among Chinese older adults: findings from a nationwide cohort study.

BACKGROUND: Dietary diversity has been suggested as a potential preventive measure against frailty in older adults, but the effect of changes in dietary diversity on frailty is unclear. This study was conducted to examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. METHODS: A total of 12,457 adults aged 65 years or older were enrolled from three consecutive and nonoverlapping cohorts from the Chinese Longitudinal Healthy Longevity Survey (the 2002 cohort, the 2005 cohort, and the 2008 cohort). DDS was calculated based on nine predefined food groups, and DDS changes were assessed by comparing scores at baseline and the first follow-up survey. We used 39 self-reported health items to assess frailty. Cox proportional hazard models were performed to examine the association between DDS change patterns and frailty. RESULTS: Participants with low-to-low DDS had the highest frailty incidence (111.1/1000 person-years), while high-to-high DDS had the lowest (41.1/1000 person-years). Compared to the high-to-high group of overall DDS pattern, participants in other DDS change patterns had a higher risk of frailty (HRs ranged from 1.25 to 2.15). Similar associations were observed for plant-based and animal-based DDS. Compared to stable DDS changes, participants with an extreme decline in DDS had an increased risk of frailty, with HRs of 1.38 (1.24, 1.53), 1.31 (1.19, 1.44), and 1.29 (1.16, 1.43) for overall, plant-based, and animal-based DDS, respectively. CONCLUSIONS: Maintaining a lower DDS or having a large reduction in DDS was associated with a higher risk of frailty among Chinese older adults. These findings highlight the importance of improving a diverse diet across old age for preventing frailty in later life.

Association of changes in waist circumference, waist-to-height ratio and weight-adjusted-waist index with multimorbidity among older Chinese adults: results from the Chinese longitudinal healthy longevity survey (CLHLS).

BACKGROUND: The association of changes in waist circumference (WC), waist-to-height ratio (WHtR) and weight-adjusted-waist index (WWI) with subsequent risk of multimorbidity remains unclear among older Chinese adults. Therefore, we aimed to assess this association by utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHODS: Our study was based on the 2011/2012 wave of the CLHLS whose follow-up surveys were conducted in 2014 and 2017/2018. A total of 2900 participants aged 65 and above at baseline were enrolled. WC, WHtR, and WWI were calculated from measured height, weight, and waist circumference. Multimorbidity refers to the coexistence of two or more of 18 chronic diseases. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) to evaluate the effect of three-year changes in WC, WHtR, and WWI on the risk of multimorbidity. RESULTS: During a mean follow-up time of 4.2 (2.0) years, 906 multimorbidity cases were identified. Compared to participants in the persistently low WC group, those in the WC gain group and the persistently high WC group had a higher multimorbidity risk with adjusted HRs (95%CI) of 1.23 (1.01-1.50) and 1.34(1.14-1.58), respectively. Participants in the WHtR gain group and the persistently high WHtR group also had higher risks of multimorbidity with HRs (95%CI) of 1.35 (1.08-1.67) and 1.27 (1.05-1.53), respectively, relative to the persistently low WHtR group. Compared to the persistently low WWI group, those in the WWI loss group had a lower risk of multimorbidity with HRs (95%CI) of 0.80 (0.66-0.98). For every standard deviation increase in WC, WHtR, and WWI over three years, the risk of multimorbidity was higher by 12% (95%CI: 1.05-1.19), 13% (95%CI: 1.06-1.20), and 12% (95%CI: 1.05-1.20), respectively. CONCLUSIONS: Associations of changes in WC, WHtR and WWI with multimorbidity are significant among older Chinese adults. The findings highlight the importance of evaluating changes in WC, WHtR, and WWI in screening and prevention of multimorbidity in older adults.

Leisure-time activities and disability among Chinese community-dwelling oldest old: evidence from the Chinese Longitudinal Healthy Longevity Study.

With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14 039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults.

Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site.

Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/ß-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/ß-tubulin-GB1 complex.

Long-term air pollutants exposure and respiratory mortality: A large prospective cohort study.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05-3.39), 1.62 (1.23-2.12), 2.06 (1.73-2.45), 1.20 (1.16-1.25), and 1.07 (1.05-1.08) per 10 µg/m3 increase in PM2.5, PM2.5-10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33-1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Emergence and evolution of drug-resistant Mycobacterium tuberculosis in eastern China: A six-year prospective study.

Understanding the emergence and evolution of drug resistance can inform public health intervention to combat tuberculosis (TB). In this prospective molecular epidemiological surveillance study from 2015 to 2021 in eastern China, we prospectively collected whole-genome sequencing and epidemiological data on TB patients. We dissect the ordering of drug resistance mutation acquisition for nine commonly used anti-TB drugs, and we found that the katG S315T mutation first appeared around 1959, followed by rpoB S450L (1969), rpsL L43A (1972), embB M306V (1978), rrs 1401 (1981), fabG1 (1982), pncA (1985) and folC (1988) mutations. GyrA gene mutations appeared after the year of 2000. We observed that the first expansion of Mycobacterium tuberculosis (M.tb) resistance population among eastern China appeared after the introduction of isoniazid, streptomycin and para-amino salicylic acid, and the second expansion after the ethambutol, rifampicin, pyrazinamide, ethionamide and aminoglycosides. We speculate these two expansions are linked with population shift historically. By geospatial analysis, we found drug-resistant isolates migrated within eastern China. With epidemiological data of clonal strains, we observed some strains can evolve continuously in individuals and transmit readily in a population. In conclusion, this study mirrored the emergence and evolution of drug-resistant M.tb in eastern China were linked to the sequence and timing of introduction of anti-TB drugs, and multiple factors may contribute to the resistant population enlarged. To resolve the epidemic of drug-resistant TB, it requires applying anti-TB drugs carefully and/or identifying resistant patients timely to prevent them from developing high-level resistance and transmitting to others.