TMEM100 acts as a TAK1 receptor that prevents pathological cardiac hypertrophy progression.

Pathological cardiac hypertrophy is the primary cause of heart failure, yet its underlying mechanisms remain incompletely understood. Transmembrane protein 100 (TMEM100) plays a role in various disorders, such as nervous system disease, pain and tumorigenesis, but its function in pathological cardiac hypertrophy is still unknown. In this study, we observed that TMEM100 is upregulated in cardiac hypertrophy. Functional investigations have shown that adeno-associated virus 9 (AAV9) mediated-TMEM100 overexpression mice attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy, including cardiomyocyte enlargement, cardiac fibrosis, and impaired heart structure and function. We subsequently demonstrated that adenoviral TMEM100 (AdTMEM100) mitigates phenylephrine (PE)-induced cardiomyocyte hypertrophy and downregulates the expression of cardiac hypertrophic markers in vitro, whereas TMEM100 knockdown exacerbates cardiomyocyte hypertrophy. The RNA sequences of the AdTMEM100 group and control group revealed that TMEM100 was involved in oxidative stress and the MAPK signaling pathway after PE stimulation. Mechanistically, we revealed that the transmembrane domain of TMEM100 (amino acids 53-75 and 85-107) directly interacts with the C-terminal region of TAK1 (amino acids 1-300) and inhibits the phosphorylation of TAK1 and its downstream molecules JNK and p38. TAK1-binding-defective TMEM100 failed to inhibit the activation of the TAK1-JNK/p38 pathway. Finally, the application of a TAK1 inhibitor (iTAK1) revealed that TAK1 is necessary for TMEM100-mediated cardiac hypertrophy. In summary, TMEM100 protects against pathological cardiac hypertrophy through the TAK1-JNK/p38 pathway and may serve as a promising target for the treatment of cardiac hypertrophy.

Remifentanil vs. dexmedetomidine for cardiac surgery patients with noninvasive ventilation intolerance: a multicenter randomized controlled trial.

BACKGROUND: The optimal sedative regime for noninvasive ventilation (NIV) intolerance remains uncertain. The present study aimed to assess the efficacy and safety of remifentanil (REM) compared to dexmedetomidine (DEX) in cardiac surgery patients with moderate-to-severe intolerance to NIV. METHODS: In this multicenter, prospective, single-blind, randomized controlled study, adult cardiac surgery patients with moderate-to-severe intolerance to NIV were enrolled and randomly assigned to be treated with either REM or DEX for sedation. The status of NIV intolerance was evaluated using a four-point NIV intolerance score at different timepoints within a 72-h period. The primary outcome was the mitigation rate of NIV intolerance following sedation. RESULTS: A total of 179 patients were enrolled, with 89 assigned to the REM group and 90 to the DEX group. Baseline characteristics were comparable between the two groups, including NIV intolerance score [3, interquartile range (IQR) 3-3 vs. 3, IQR 3-4, p = 0.180]. The chi-squared test showed that mitigation rate, defined as the proportion of patients who were relieved from their initial intolerance status, was not significant at most timepoints, except for the 15-min timepoint (42% vs. 20%, p = 0.002). However, after considering the time factor, generalized estimating equations showed that the difference was statistically significant, and REM outperformed DEX (odds ratio = 3.31, 95% confidence interval: 1.35-8.12, p = 0.009). Adverse effects, which were not reported in the REM group, were encountered by nine patients in the DEX group, with three instances of bradycardia and six cases of severe hypotension. Secondary outcomes, including NIV failure (5.6% vs. 7.8%, p = 0.564), tracheostomy (1.12% vs. 0%, p = 0.313), ICU LOS (7.7 days, IQR 5.8-12 days vs. 7.0 days, IQR 5-10.6 days, p = 0.219), and in-hospital mortality (1.12% vs. 2.22%, p = 0.567), demonstrated comparability between the two groups. CONCLUSIONS: In summary, our study demonstrated no significant difference between REM and DEX in the percentage of patients who achieved mitigation among cardiac surgery patients with moderate-to-severe NIV intolerance. However, after considering the time factor, REM was significantly superior to DEX. Trial registration ClinicalTrials.gov (NCT04734418), registered on January 22, 2021. URL of the trial registry record: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S000AM4S&selectaction=Edit&uid=U00038YX&ts=3&cx=eqn1z0 .

Sandwich Layer-Modified Ω-Shaped Fiber-Optic LSPR Enables the Development of an Aptasensor for a Cytosensing-Photothermal Therapy Circuit.

The metastasis of cancer cells is a principal cause of morbidity and mortality in cancer. The combination of a cytosensor and photothermal therapy (PTT) cannot completely eliminate cancer cells at one time. Hence, this study aimed to design a localized surface plasmonic resonance (LSPR)-based aptasensor for a circuit of cytosensing-PTT (COCP). This was achieved by coating a novel sandwich layer of polydopamine/gold nanoparticles/polydopamine (PDA/AuNPs/PDA) around the Ω-shaped fiber-optic (Ω-FO). The short-wavelength peak of the sandwich layer with strong resonance exhibited a high refractive index sensitivity (RIS). The modification with the T-shaped aptamer endowed FO-LSPR with unique characteristics of time-dependent sensitivity enhancement behavior for a sensitive cytosensor with the lowest limit of detection (LOD) of 13 cells/mL. The long-wavelength resonance peak in the sandwich layer appears in the near-infrared region. Hence, the rate of increased localized temperature of FO-LSPR was 160 and 30-fold higher than that of the bare and PDA-coated FO, indicating strong photothermal conversion efficiency. After considering the localized temperature distribution around the FO under the flow environment, the FO-LSPR-enabled aptasensor killed 77.6% of cancer cells in simulated blood circulation after five cycles of COCP. The FO-LSPR-enabled aptasensor improved the efficiency of the cytosensor and PTT to effectively kill cancer cells, showing significant potential for application in inhibiting cancer metastasis.

Highly efficient recycling of polyester wastes to diols using Ru and Mo dual-atom catalyst.

The chemical recycling of polyester wastes is of great significance for sustainable development, which also provides an opportunity to access various oxygen-containing chemicals, but generally suffers from low efficiency or separation difficulty. Herein, we report anatase TiO2 supported Ru and Mo dual-atom catalysts, which achieve transformation of various polyesters into corresponding diols in 100% selectivity via hydrolysis and subsequent hydrogenation in water under mild conditions (e.g., 160 °C, 4 MPa). Compelling evidence is provided for the coexistence of Ru single-atom and O-bridged Ru and Mo dual-atom sites within this kind of catalysts. It is verified that the Ru single-atom sites activate H2 for hydrogenation of carboxylic acid derived from polyester hydrolysis, and the O-bridged Ru and Mo dual-atom sites suppress hydrodeoxygenation of the resultant alcohols due to a high reaction energy barrier. Notably, this kind of dual-atom catalysts can be regenerated with high activity and stability. This work presents an effective way to reconstruct polyester wastes into valuable diols, which may have promising application potential.

Carbon and Nutrient Limitations of Microbial Metabolism in Xingkai Lake, China: Abiotic and Biotic Drivers.

Microbial communities are crucial for water quality and biogeochemical cycling in freshwaters. Microbes secrete extracellular enzymes to decompose organic matter for their needs of nutrients and scarce elements. Yet, there is a lack of knowledge on microbial metabolic limitations in freshwaters, especially in lake sediments. Here, we examined the carbon, nitrogen, and phosphorus-acquiring extracellular enzyme activities and the bacterial and fungal communities of 30 sediments across Xingkai Lake, the largest freshwater lake in Northeast Asia. We further analyzed the microbial metabolic limitations via extracellular enzyme stoichiometry and explored the direct and indirect effects of abiotic and biotic factors on the limitations. We found that microbial metabolisms were primarily limited by phosphorus in Xingkai Lake. For instance, microbial carbon and phosphorus limitations were closely correlated to abiotic factors like water depth, total dissolved solids, sediment total carbon, and conductivity. The metabolic limitations were also affected by biotic factors, such as showing positive relationships with the alpha and beta diversity of bacteria, and with the beta diversity of fungi. In addition, community compositions of bacteria and fungi were mainly correlated to abiotic factors such as total carbon and dissolved organic carbon, respectively. Collectively, microbial metabolic limitations were affected directly or indirectly by abiotic factors and microbial communities. Our findings indicate that microbial metabolic limitations are not only driven by bacteria and fungi but also by abiotic factors such as water depth and total nitrogen, and thus provide empirical evidence for effective management of freshwater lakes under climate warming and intensified human activities.

Oral behaviors and anxiety are significant predictors of jaw function limitation in patients with anterior disc displacement without reduction.

OBJECTIVE: We aimed to describe jaw function characteristics in patients with anterior disc displacement without reduction (ADDWoR) using the jaw function limitation scale (JFLS), and to investigate the effects of biopsychosocial risk factors on limited jaw function. DESIGN: In this cross-sectional study of 636 patients with ADDWoR (females, 568; males, 68), we used the JFLS to assess jaw function. Behavioral, psychological, sociodemographic, and biomedical data were collected. Multivariate logistic regression analysis was used to determine risk factors affecting limited jaw function. A receiver operating characteristic curve was used to evaluate the predictive effect of these risk factors. RESULTS: ADDWoR-associated limitations included restricted jaw mobility and mastication, which exceeded median global functional limitations scale scores, especially mouth opening to bite an apple and chewing tough food. Females had greater limitations in jaw mobility, verbal and emotional communication, and overall. Multivariate logistic regression analysis findings indicated that oral behaviors, anxiety, sex, pain intensity, and maximal mouth opening (MMO) were predictive of limited jaw function (area under the curve, 72 %). CONCLUSION: Patients with ADDWoR reported mastication and jaw mobility restrictions, with females having more pronounced limitations, and specific risk factors identified as significant predictors of jaw function limitations. Along with pain relief and improvement in MMO, appropriate psychological counseling and oral behavioral correction facilitates recovery of jaw function in such patients.

Ω-Shaped fiber optic LSPR coated with hybridized nanolayers for tumor cell sensing and photothermal treatment.

Circulating tumor cell (CTC) in the blood is the main cause of cancer metastasis for death in cancer patients. It is extremely important for cancer diagnosis at an early stage and treatment to simultaneously detect and kill the CTCs. In this work, a new hybridized nanolayer, namely gold nanoparticle/gold nanorods@ Polydopamine (AuNPs/AuNRs@PDA), was coated on the Ω-shaped fiber optics (Ω-FO) for localized surface plasmonic resonance (LSPR) to perform tumor cell sensing and photothermal treatment (PTT). The PDA nanolayer was formed on a bare fiber optic through the self-polymerization of dopamine under mild conditions. The AuNRs and AuNPs were absorbed on the surface of the PDA nanolayer to form a hybridized nanolayer. The hybridized nanolayer-modified Ω-FO LSPR exhibited a high refractive index sensitivity (RIS) of 37.59 (a.u/RIU) and photothermal conversion efficiency. After being modified with the recognition element of aptamer, the Ω-FO LSPR was used to develop a sensitive and specifical tumor cell sensing. Under the irradiation of near-infrared light (NIR) laser, the Ω-FO LSPR can kill the captured tumor cells with the apoptotic/necrotic rate of 62.6 % and low side-effect for the nontarget cells. The FO LSPR sensor realized the dual functions of CTC sensing and PTT, which provided a new idea for the early diagnosis and treatment of cancer.

GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.

BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.

Enhancing the Thermal Stability and Enzyme Activity of Ketopantoate Hydroxymethyltransferase through Interface Modification Engineering.

Ketopantoate hydroxymethyltransferase (KPHMT) plays a pivotal role in d-pantothenic acid biosynthesis. Most KPHMTs are homodecamers with low thermal stability, posing challenges for protein engineering and limiting output enhancement. Previously, a high-enzyme activity KPHMT mutant (K25A/E189S) from Corynebacterium glutamicum was screened as mother strain (M0). Building upon this strain, our study focused on interface engineering modifications, employing a multifaceted approach including integrating folding-free energy calculation, B-factor analysis, and conserved site analysis. Preliminary screening led to the selection of five mutants in the interface─E106S, E98T, E98N, S247I, and S247D─showing improved thermal stability, culminating in the double-site mutant M8 (M0-E98N/S247D). M8 exhibited a T1/2 value of 288.79 min at 50 °C, showing a 3.29-fold increase compared to M0. Meanwhile, the Tm value of M8 was elevated from 53.2 to 59.6 °C. Investigations of structural and molecular dynamics simulations revealed alterations in surface electrostatic charge distribution and the formation of increased hydrogen bonds between subunits, contributing to enhanced thermal stability. This investigation corroborates the efficacy of interface engineering modifications in bolstering KPHMT stability while showing its potential for positively impacting industrial d-pantothenic acid synthesis.

Identification of hyperthermophilic D-allulose 3-epimerase from Thermotoga sp. and its application as a high-performance biocatalyst for D-allulose synthesis.

D-Allulose 3-epimerase (DAE) is a vital biocatalyst for the industrial synthesis of D-allulose, an ultra-low calorie rare sugar. However, limited thermostability of DAEs hinders their use at high-temperature production. In this research, hyperthermophilic TI-DAE (Tm = 98.4 ± 0.7 ℃) from Thermotoga sp. was identified via in silico screening. A comparative study of the structure and function of site-directed saturation mutagenesis mutants pinpointed the residue I100 as pivotal in maintaining the high-temperature activity and thermostability of TI-DAE. Employing TI-DAE as a biocatalyst, D-allulose was produced from D-fructose with a conversion rate of 32.5%. Moreover, TI-DAE demonstrated excellent catalytic synergy with glucose isomerase CAGI, enabling the one-step conversion of D-glucose to D-allulose with a conversion rate of 21.6%. This study offers a promising resource for the enzyme engineering of DAEs and a high-performance biocatalyst for industrial D-allulose production.

Transient social-ecological dynamics reveal signals of decoupling in a highly disturbed Anthropocene landscape.

Understanding the transient dynamics of interlinked social-ecological systems (SES) is imperative for assessing sustainability in the Anthropocene. However, how to identify critical transitions in real-world SES remains a formidable challenge. In this study, we present an evolutionary framework to characterize these dynamics over an extended historical timeline. Our approach leverages multidecadal rates of change in socioeconomic data, paleoenvironmental, and cutting-edge sedimentary ancient DNA records from China's Yangtze River Delta, one of the most densely populated and intensively modified landscapes on Earth. Our analysis reveals two significant social-ecological transitions characterized by contrasting interactions and feedback spanning several centuries. Initially, the regional SES exhibited a loosely connected and ecologically sustainable regime. Nevertheless, starting in the 1950s, an increasingly interconnected regime emerged, ultimately resulting in the crossing of tipping points and an unprecedented acceleration in soil erosion, water eutrophication, and ecosystem degradation. Remarkably, the second transition occurring around the 2000s, featured a notable decoupling of socioeconomic development from ecoenvironmental degradation. This decoupling phenomenon signifies a more desirable reconfiguration of the regional SES, furnishing essential insights not only for the Yangtze River Basin but also for regions worldwide grappling with similar sustainability challenges. Our extensive multidecadal empirical investigation underscores the value of coevolutionary approaches in understanding and addressing social-ecological system dynamics.

Analysis of risk factors and interactions for pain in temporomandibular disorder: A cross-sectional study.

BACKGROUND: Risk factors for temporomandibular disorder (TMD) pain remain unclear. OBJECTIVES: This study aimed to identify risk factors for TMD pain using a biopsychosocial model and to investigate interactions between potential risk factors-oral behaviours (OBs), psychological factors and sleep quality-and their direct and indirect effects on TMD pain. METHODS: This was a cross-sectional study of 488 patients with TMDs (422 women; 30.8 ± 9.4 years). Pain was assessed using the Numerical Rating Scale. Demographic, behavioural, psychological and biomedical data were collected through clinical examination, face-to-face interviews and questionnaires. Multiple linear regression analysis was used to identify factors associated with TMD pain. Mediation and moderation analysis were used to evaluate interactions between variables. Significant mediation ('0' not included in the 95% confidence interval (CI)) and moderation (p < .05) effects on TMD pain were identified. RESULTS: Marital status, diagnosis subgroup, previous medication use, depression and sleep quality were significant risk factors for TMD pain (p < .05). Significant mediation effects were observed as follows: depression and sleep quality mediated the association between OBs and pain; sleep quality mediated the association between somatization, depression, anxiety and pain; and depression mediated the association between sleep quality and pain (all 95% CI did not contain '0'). CONCLUSIONS: (1) Marital status, diagnosis subgroup, previous medication use, depression and sleep quality were associated with TMD pain. (2) OBs can exacerbate pain by promoting depression and reducing sleep quality. Psychological factors and sleep quality can interact to exacerbate pain.

[Accumulation of microbial necromass carbon and their contribution to soil organic carbon in different vegetation types on the Loess Plateau, Northwest China]. / é»„åœŸé«˜åŽŸä¸åŒæ¤è¢«ç±»åž‹åœŸå£¤å¾®ç”Ÿç‰©æ®‹ä½“ç¢³çš„ç§¯ç´¯åŠå ¶å¯¹æœ‰æœºç¢³çš„è´¡çŒ®.

Microbial necromass carbon (MNC) is an important contributor to soil organic carbon (SOC). Soil carbon storage has increased significantly since the return of farmland to forestland (grassland) on the Loess Plateau. However, the contribution of MNC to SOC accumulation in different vegetation types and the influence factors remain unclear. Herein, we used the biomarker (amino sugar) technique to determine the MNC content and analyzed the influencing factors in 0-5 cm and 5-20 cm soil layers of natural grassland, shrubland (Caragana microphylla), and forestland (Quercus liaodongensis) in the Loess Plateau. The results showed that: 1) the soil pH decreased significantly from grassland to shrubland and then to forestland within the same soil layer. However, the SOC, total nitrogen (TN), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) contents showed a reverse trend, with forestland displaying the highest values followed by shrubland and then grassland. The 0-5 cm had significantly higher values than the 5-20 cm depth. 2) The MNC contents varied 0.69-16.41 g·kg-1 in the two soil horizons of the three vegetation types. There were significant increases in the contents of bacterial necromass carbon (BNC), fungal necromass carbon (FNC), and MNC in the 0-5 cm soil from grassland, shrubland to forestland. The contents of MBC were 1.9 times higher in forestland than in shrubland, and 3.2 times higher in shrubland than in grassland. In the 5-20 cm soil layer, the contents of FNC and MBC were significantly higher in the forestland than in the shrubland and grassland. The FNC content was significantly higher than that of the BNC, ranging from 1.16 to 9.83 times greater than the BNC. 3) The contribution of MNC to SOC was 0.6 and 0.7 times higher in shrubland and forestland than in grassland, respectively, with FNC accounting for 15.2%-42.7%, and BNC accounting for 1.4%-7.4%. 4) pH, TN, MBC, and MBN were important factors that influenced MNC accumulation. In summary, the variation in vegetation type altered soil nutrients, microbial activity, and soil pH, resulting in forestland and shrubland being more beneficial to the formation and accumulation of MNC, which was dominated by fungi, compared to grassland.

Modification of nitrilase based on computer screening and efficient biosynthesis of 4-cyanobenzoic acid.

4-cyanobenzoic acid serves as a crucial intermediate for the synthesis of various high-value organic compounds. The enzymatic hydrolysis of terephthalonitrile to produce 4-cyanobenzoic acid using nitrilase offers the advantages of a simple reaction pathway, environmental friendliness, and easy product separation. In order to efficiently develop nitrilases that meet industrial production requirements, the virtual screening method used in the study is established and mature. From a total of 371 amino acids in the nitrilase AfNIT, which exhibits activity in terephthalonitrile hydrolysis, three candidate sites (F168, S192, and T201) were identified, and a "small and accurate" mutant library was constructed. The triple mutant F168V/T201N/S192F was screened from this small mutant library with a specific activity of 227.3 U mg-1 , which was 3.8 times higher than that of the wild-type AfNIT. Using the whole-cell biocatalyst containing the mutant F168V/T201N/S192F, terephthalonitrile was successfully hydrolyzed at a concentration of 150 g L-1 to produce 4-cyanobenzoic acid with a final yield of 170.3 g L-1 and a conversion rate of 98.7%. The obtained nitrilase mutant F168V/T201N/S192F in this study can be effectively applied in the biomanufacturing of 4-cyanobenzoic acid using terephthalonitrile as a substrate. Furthermore, the results also demonstrate the significant improvement in predictive accuracy achieved through the latest AI-assisted computer simulation methods. This approach represents a promising and feasible new technological pathway for assisting enzyme engineering research, laying a theoretical foundation for other related studies.

Construction of an instrument to enable the assessment of the risk of falls in older outpatients: A quantitative methodological study.

OBJECTIVES: To develop an instrument to facilitate the risk assessment of falls in older outpatients. DESIGN: A quantitative methodological study using the cross-sectional data. METHODS: This study enrolled 1988 older participants who underwent comprehensive geriatric assessment (CGA) in an outpatient clinic from May 2020 to November 2022. The history of any falls (≥1 falls in a year) and recurrent falls (≥2 falls in a year) were investigated. Potential risk factors of falls were selected by stepwise logistic regression, and a screening tool was constructed based on nomogram. The tool performance was compared with two reference tools (Fried Frailty Phenotype; CGA with 10 items, CGA-10) by using receiver operating curves, sensitivity (Sen), specificity (Spe), and area under the curve (AUC). RESULTS: Age, unintentional weight loss, depression measured by the Patient Health Questionnaire-2, muscle strength measured by the five times sit-to-stand test, and stand balance measured by semi- and full-tandem standing were the most important risk factors for falls. A fall risk screening tool was constructed with the six measurements (FRST-6). FRST-6 showed the best AUC (Sen, Spe) of 0.75 (Sen = 0.72, Spe = 0.69) for recurrent falls and 0.65 (Sen = 0.74, Spe = 0.48) for any falls. FRST-6 was comparable to CGA-10 and outperformed FFP in performance. CONCLUSIONS: Age, depression, weight loss, gait, and balance were important risk factors of falls. The FRST-6 tool based on these factors showed acceptable performance in risk stratification. IMPACT: Performing a multifactorial assessment in primary care clinics is urgent for falls prevention. The FRST-6 provides a simple and practical way for falls risk screening. With this tool, healthcare professionals can efficiently identify patients at risk of falling and make appropriate recommendations in resource-limited settings. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was received, due to our study design.

Combined effects of vitamin D deficiency and systemic inflammation on all-cause mortality and cause-specific mortality in older adults.

BACKGROUND: Vitamin D deficiency and systemic inflammation share common pathological mechanisms in muscle loss, cardio-pulmonary function decline, and abnormal metabolism, which are linked to chronic conditions, senescence, and early mortality. However, their combined effect on mortality in older adults has not been well established. This study longitudinal aimed to explore the independent and combined associations of serum 25-hydroxyvitamin D [25(OH)D] and high sensitivity C-reactive protein (hs-CRP) with mortality risk in Chinese community-based older people. METHODS: 3072 older adults (86.07 ± 11.87 years, 54.52% female) from the Chinese Longitudinal Healthy Longevity Survey (2012-2018) were enrolled. Baseline 25(OH)D and hs-CRP levels were collected, and survival information was recorded in the 2014 and 2018 follow-up waves. Cox proportional hazard regressions were conducted to explore the associations between 25(OH)D, hs-CRP, and mortality. Demographic characteristics, health behaviors, and chronic disease biomarkers were adjusted. RESULTS: During 10,622.3 person-years of follow-up (median: 3.51 years), 1321 older adults died, including 448 deaths due to cardiovascular disease (CVD). Increased mortality risk was associated with lower 25(OH)D and higher hs-CRP quantiles, even after adjusting for each other and multiple covariates (all P-trend < 0.05). In combined analyses, the highest all-cause mortality (HR: 2.18, 95% CI: 1.73 ~ 2.56), CVD mortality (HR: 2.30, 95% CI: 1.64 ~ 3.21), and non-CVD mortality (HR: 2.19, 95% CI: 1.79 ~ 2.49) were obtained in participants with both 25(OH)D deficiency (< 50 nmol/L) and high hs-CRP (≥ 3.0 mg/L), respectively. We observed significant additive interactions of 25(OH)D and hs-CRP on all-cause mortality and non-CVD mortality (RERIS>0). CONCLUSIONS: Low 25(OH)D and high hs-CRP, both independently and jointly, increase mortality risk in Chinese community-dwelling older adults. Thus, priority should be given to early detection and appropriate intervention in older individuals with combined vitamin D deficiency and systemic inflammation. Molecular mechanisms of related adverse health effect are worthy of further investigation.

Atomic Engineering of Single-Atom Nanozymes for Biomedical Applications.

Single-atom nanozymes (SAzymes) showcase not only uniformly dispersed active sites but also meticulously engineered coordination structures. These intricate architectures bestow upon them an exceptional catalytic prowess, thereby captivating numerous minds and heralding a new era of possibilities in the biomedical landscape. Tuning the microstructure of SAzymes on the atomic scale is a key factor in designing targeted SAzymes with desirable functions. This review first discusses and summarizes three strategies for designing SAzymes and their impact on reactivity in biocatalysis. The effects of choices of carrier, different synthesis methods, coordination modulation of first/second shell, and the type and number of metal active centers on the enzyme-like catalytic activity are unraveled. Next, a first attempt is made to summarize the biological applications of SAzymes in tumor therapy, biosensing, antimicrobial, anti-inflammatory, and other biological applications from different mechanisms. Finally, how SAzymes are designed and regulated for further realization of diverse biological applications is reviewed and prospected. It is envisaged that the comprehensive review presented within this exegesis will furnish novel perspectives and profound revelations regarding the biomedical applications of SAzymes.

Combined associations of cognitive impairment and psychological resilience with all-cause mortality in community-dwelling older adults.

BACKGROUND: Cognitive impairment and psychological resilience are closely related in older adults, but their combined effect on mortality has not been reported. Using a nationally representative sample from the Chinese Longitudinal Healthy Longevity Study, this study examined the interactions between cognitive impairment and psychological resilience and their associations with overall survival. METHODS: A total of 32,349 community-dwelling older adults (86.85 ± 11.16 years, 56.06 % female) were enrolled in 1998, 2000, 2002, 2005, 2008, 2011, and 2014; all participants were followed until 2018. Cognitive function and psychological resilience were assessed using the Mini-Mental State Examination (MMSE) and the 7-item psychological resilience questionnaire (PRQ), respectively. Illiterate subjects with an MMSE score <18, or literate subjects with an MMSE score <24 were defined as having cognitive impairment. Cox proportional risk regressions were used to analyze the association of cognitive impairment and psychological resilience with all-cause mortality. RESULTS: After 146,993.52 person-years of follow-up, 23,349 older adults died. Both MMSE and PRQ scores (as continuous variables) were negatively associated with mortality risk after adjusting for all covariates. The hazard ratio (HR) of all-cause mortality for cognitive impairment was not significantly moderated by levels of psychological resilience (P-interaction = 0.094). In joint analyses, participants with combined cognitive impairment and low resilience (by the median of PRQ: < 25 points) had the highest risk of mortality (adjusted-HR: 1.56, 95%CI: 1.48-1.61), which was higher than that of patients with either condition alone. There was a significant additive interaction effect of cognitive impairment and low resilience on all-cause mortality (relative excess risk due to interaction: 0.11, 95 % CI: 0.09-0.13), and 7 % of the overall mortality risk was attributable to their synergistic effect. CONCLUSIONS: Cognitive impairment and low resilience are synergistically associated with increased risk of all-cause mortality in community-dwelling older adults. The potential mechanisms underlying this combined effect warrant further exploration.

Sahara's surface transformation forced an abrupt hydroclimate decline and Neolithic culture transition in northern China.

The remote forcing from land surface changes in the Sahara is hypothesized to play a pivotal role in modulating the intensity of the East Asian summer monsoon (EASM) through ocean-atmospheric teleconnections. This modulation has far-reaching consequences, particularly in facilitating societal shifts documented in northern China. Here, we present a well-dated lake-level record from the Daihai Lake Basin in northern China, providing quantitative assessments of Holocene monsoonal precipitation and the consequent migrations of the northern boundary of the EASM. Our reconstruction, informed by a water-and-energy balance model, indicates that annual precipitation reached ∼700 mm during 8-5 ka, followed by a rapid decline to ∼550 mm between 5 and 4 ka. This shift coherently aligns with a significant ∼300 km northwestward movement of the EASM northern boundary during the Middle Holocene (MH), in contrast to its current position. Our findings underscore that these changes cannot be entirely attributed to orbital forcing, as corroborated by simulation tests. Climate model simulations deployed in our study suggest that the presence of the Green Sahara during the MH significantly strengthened the EASM and led to a northward shift of the monsoon rainfall belt. Conversely, the Sahara's reversion to a desert landscape in the late Holocene was accompanied by a corresponding southward retraction of monsoon influence. These dramatic hydroclimate changes during ∼5-4 ka likely triggered or at least contributed to a shift in Neolithic cultures and societal transformation in northern China. With decreasing agricultural productivity, communities transitioned from millet farming to a mixed rainfed agriculture and animal husbandry system. Thus, our findings elucidate not only the variability of the EASM but also the profound implications of a remote forcing, such as surface transformations of the Sahara, on climatic changes and cultural evolution in northern China.