Mediating role of inflammatory indicators in the association between sleep status and blood pressure in centenarians: evidence from China Hainan Centenarian Cohort Study.

Objectives: To conduct a comprehensive analysis in Hainan centenarians on the link between sleep status and their blood pressure status. Furthermore, the study also aims to explore how inflammatory indicators may mediate the relationship. Methods: The China Hainan Centenarians Cohort Study (CHCCS) collected baseline data on sleep status, inflammatory indicators, and blood pressure data. The study used a mediation model to investigate how inflammatory indicators mediate the relationship between sleep status and blood pressure status. Result: In this study, a total of 967 centenarians were included. The prevalence of hypertension among the centenarians was 71.4%. The analysis showed that centenarians with poor sleep quality had a 43% higher risk of hypertension compared to those with normal sleep quality (OR = 1.43, 95% CI: 1.03-1.97). Additionally, centenarians with nighttime sleep durations of ≤ 6 h or > 9 h had higher proportions of high pulse pressure (PP), with OR values of 1.76 (95% CI: 1.18-2.63) and 2.07 (95% CI: 1.34-3.19), respectively. Mediation analysis illustrated that complement C3 played a mediating role in the relationship between sleep quality and hypertension, with an effect ratio of 2.4%. Similarly, lymphocyte count, the neutrophil-to-lymphocyte ratio (NLR), and the systemic immune-inflammation index (SII) were identified as mediating factors in the association between nighttime sleep duration and high PP, with effect ratios of 91.22%, 36.93%, and 0.20%, respectively. Conclusion: In centenarians, poor sleep quality raises the risk of hypertension, with complement C3 as a mediator. Additionally, nighttime sleep durations of ≤ 6 h or > 9 h increases the risk of high PP, mediated by lymphocyte count, NLR, and SII.

Two-dimensional Janus XWZAZ' (X = S, Se, Te; A = Si, Ge; Z, Z' = N, P, As): candidates for photocatalytic water splitting and piezoelectric materials.

Due to their extraordinary properties, particularly the presence of an inherent electric field that effectively suppresses the recombination of photogenerated carriers, Janus two-dimensional (2D) materials exhibit strong light absorption and high solar-to-hydrogen conversion efficiency, making them promising candidates for photocatalytic water splitting applications. In this study, we conducted first-principles calculations to investigate the layers XWZAZ' (X = S, Se, Te; A = Si, Ge; Z, Z' = N, P, As; Z ≠ Z'). Out of 36 possible structures, 25 were found to be stable in terms of their dynamic, thermal, and mechanical properties. Among these 25 stable structures, 22 exhibit semiconductor behavior. Notably, 9 of these semiconductor structures demonstrate excellent photocatalytic and light absorption properties. These 9 photocatalysts possess remarkable light absorption rates (∼23%), high solar-to-hydrogen energy conversion efficiencies (38.447%), ultra-high carrier mobilities (101 596.37 cm2 s-1 V-1), and spontaneous hydrogen evolution reaction (HER) capabilities. Furthermore, all 22 semiconductor structures display significant piezoelectric responses both in-plane and out-of-plane, and biaxial strain has a considerable impact on the properties of the 25 stable structures. This study not only provides potential candidate materials for photocatalytic and piezoelectric applications but also offers theoretical guidance for addressing energy crises and environmental pollution challenges.

Association between serum IgM and all-cause mortality risk in Chinese centenarians: a prospective cohort study.

BACKGROUND: We investigated the associations between IgM, IgG, IgA, and IgE levels and all-cause mortality risk in Chinese centenarians. METHODS: All participants were from the China Hainan Centenarian Cohort Study. Eligible participants were divided into quartiles based on their IgM, IgG, IgA, and IgE levels. We used restricted cubic spline analyses, Cox regression analyses, and Kaplan-Meier survival curves to analyze associations between IgM, IgG, IgA, and IgE and all-cause mortality risk. RESULTS: A total of 906 centenarian participants were included in this study (81.2% female; median age, 102 years). During a median follow-up of 30.1 months, 838 (92.5%) participants died. Restricted cubic spline analysis revealed a nonlinear relationship ("L" type) between serum IgM level and all-cause mortality. Compared with the higher three quartiles of serum IgM level, the lowest quartile was associated with a higher risk of death (Q1 versus Q2-Q4: HR, 1.365; 95% CI, 1.166-1.598; P < 0.001). Among individuals for whom IgM < 0.708 g/L (Q1), the risk of all-cause mortality was 36.5% higher. Kaplan-Meier analyses showed that centenarians with lower serum IgM levels had significantly shorter median survival time (Q1 versus Q2-Q4: 26 months versus 32 months, log-rank P = 0.001). CONCLUSION: Serum IgM levels in centenarians significantly correlated with the risk of death, suggesting that they are suitable for predicting the overall risk of death in centenarians and can be used as an independent predictor of death.

Ultra-efficient removal of aqueous hexavalent chromium by activated biochar nanoparticles derived from squid ink.

Biochar have been recognized as efficient and renewable carbon sorbents, which attracted much attention on Cr contamination remediation in wastewater. In this study, we propose a cost-effective one-step strategy to synthesize activated biochar nanoparticles derived from squid ink (AS-BC) for aqueous Cr(VI) removal. The results demonstrated that AS-BC achieved a removal rate of 24.29 h-1 at 700 °C (400-times higher than the unmodified one). This was also a state-of-the-art removal performance for aqueous Cr(VI) compared to other reported materials. AS-BC possessed an enormous specific surface (2408 m2/g at 700 °C) with abundant O- and N-containing groups, condensed aromatic structures, and high electron transfer capacity (3.64 and 2.13 mmol e-/g for EAC and EDC at 700 °C), contributing to the ultra-efficient removal of Cr(VI) by synergistic adsorption and reduction. AS-BC absorbed Cr(VI) in the form of HCrO4- by electrostatic attraction with protonated amine-N and hydroxy (-NH3+ and -OH2+) groups and Cr(III) in the form of Cr3+ by complexation with amine-N and hydroxy groups. With a hydroxy-quinone and conjugated π-electron system, AS-BC served as mediator and shuttle to accelerate electron transfer in Cr(VI) reduction with an electron donor. Therefore, our findings highlight the immense potential of AS-BC biochar nanoparticles represent a potential alternative for high-performance Cr(VI) remediation in wastewater.

Semaglutide ameliorates Alzheimer's disease and restores oxytocin in APP/PS1 mice and human brain organoid models.

AIMS: To investigate the therapeutic effects and mechanisms of Semaglutide in Alzheimer's disease (AD), and identify its potential targets. METHODS: We systematically evaluated the effect of Semaglutide on Alzheimer's disease (AD), using both mice and human organoid models. RESULTS: Behavioral analyses on APP/PS1 mice demonstrated that Semaglutide improved the cognitive capabilities, particularly in the learning and memory domains. Biochemical investigations further highlighted its role in reducing amyloid plaque deposition and down-regulating the expression of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) expression in the mouse brain tissues. Meanwhile, oxytocin (OXT) was up-regulated after Semaglutide treatment. Subsequent studies using human AD-brain organoids (BOs) models revealed that, upon Semaglutide treatment, these AD-BO models also exhibited reduced levels of amyloid-beta (Aß), phosphorylated Tau (p-Tau) and GFAP expression as well as increased OXT level. CONCLUSIONS: Semaglutide can ameliorate Alzheimer's disease in pre-clinical models, suggesting the promising therapeutic potential in AD patients.

Curcumin triggers the Wnt/ß-catenin pathway and shields neurons from injury caused by intermittent hypoxia.

The objective of this study was to explore the molecular basis through which Curcumin (Cur) mitigates neuronal damage caused by obstructive sleep apnea (OSA). HT22 was used to simulate intermittent hypoxia (IH) injury and explore the effect of Cur on these cells. We evaluated the cell viability, cytotoxicity, apoptosis, proliferation, and Wnt/ß-catenin (WßC) pathway. IWR-1 was used to block the pathway and investigate the protective mechanism of Cur. We constructed an in vivo model of IH to validate the results of the cellular experiments. IH accelerated apoptosis and cytotoxicity, suppressed proliferation, and decreased the activity of the WßC pathway. Cur can significantly improve cell viability, reduce apoptosis rate and cell toxicity, promote cell proliferation, and up-regulate the WßC. After blocking the WßC pathway, the proliferative effect of Cur was observably weakened. In vivo, IH caused hippocampal damage and inhibited WßC pathway activity in mice, which was ameliorated by Cur treatment. This implies that Cur could be a novel treatment option for neurological impairment brought on by OSA.

Smoking cessation and mortality risk reduction in older adults with long-term smoking history.

BACKGROUND: The association between smoking cessation and decreased mortality existed among former smokers has been well documented. However, evidence is limited for smokers with long-term exposure. This study aims to quantify the association between smoking cessation and mortality by years since quitting in older adults with long-term smoking history. METHODS: Data from Beijing Healthy Aging Cohort Study (BHACS), conducted among communities aged over 55 years old at recruitment, were collected via questionnaire between July 2009 and September 2015 and followed up for all-cause and cancer mortality until March 2021. Self-reported smoking status and years since quitting were collected at baseline. Cox proportional hazards models were used to examine the association between smoking cessation and all-cause and cancer mortality. RESULTS: A total of 11 235 participants (43.9% male) were included, with a mean age of 70.35 (SD 7.71) years. Former smokers comprised 31.7% of the cohort, with a median smoking duration of 43 (IQR: 34-50) years. During 71 573 person-years of follow-up, there were 1 617 deaths (14.4% of the total cohort), of which 872 (17.7%) occurred among male participants. Compared with never smokers, HR (95%CI) for participants who current smoked was 2.898 (2.092-4.013); quit smoking less than 10 years (medians [quartiles] 4 [1, 7] years) before recruitment was 2.738(1.972-3.802); 10 to 20 years (16 [13, 20] years), 1.807(1.286-2.540); and 20 years or more (30 [25, 37] years), 1.293(0.981-1.705). The risk of all-cause and cancer mortality decreased gradually over years since quitting. Quitting less than 10 years, 10 to 20 years and 20 years or more, former smokers avoided an estimated 8.4%, 57.5% and 84.6% of excess all-cause mortality associated with current smoking, respectively. The association between smoking cessation and decreased mortality was observed among former smokers regardless of smoking history. CONCLUSIONS: In this study, current smoking was associated with nearly triple the mortality risk compared to never smoking. Smoking cessation, even after a long-term smoking history, was associated with significant decreases in the relative excess mortality linked to continuing smoking. The association were more pronounced in men.

PAM-relaxed and temperature-tolerant CRISPR-Mb3Cas12a single transcript unit systems for efficient singular and multiplexed genome editing in rice, maize, and tomato.

Class 2 Type V-A CRISPR-Cas (Cas12a) nucleases are powerful genome editing tools, particularly effective in A/T-rich genomic regions, complementing the widely used CRISPR-Cas9 in plants. To enhance the utility of Cas12a, we investigate three Cas12a orthologs-Mb3Cas12a, PrCas12a, and HkCas12a-in plants. Protospacer adjacent motif (PAM) requirements, editing efficiencies, and editing profiles are compared in rice. Among these orthologs, Mb3Cas12a exhibits high editing efficiency at target sites with a simpler, relaxed TTV PAM which is less restrictive than the canonical TTTV PAM of LbCas12a and AsCas12a. To optimize Mb3Cas12a, we develop an efficient single transcription unit (STU) system by refining the linker between Mb3Cas12a and CRISPR RNA (crRNA), nuclear localization signal (NLS), and direct repeat (DR). This optimized system enables precise genome editing in rice, particularly for fine-tuning target gene expression by editing promoter regions. Further, we introduced Arginine (R) substitutions at Aspartic acid (D) 172, Asparagine (N) 573, and Lysine (K) 579 of Mb3Cas12a, creating two temperature-tolerant variants: Mb3Cas12a-R (D172R) and Mb3Cas12a-RRR (D172R/N573R/K579R). These variants demonstrate significantly improved editing efficiency at lower temperatures (22 °C and 28 °C) in rice cells, with Mb3Cas12a-RRR showing the best performance. We extend this approach by developing efficient Mb3Cas12a-RRR STU systems in maize and tomato, achieving biallelic mutants targeting single or multiple genes in T0 lines cultivated at 28 °C and 25 °C, respectively. This study significantly expands Cas12a's targeting capabilities in plant genome editing, providing valuable tools for future research and practical applications.

Fe2O3, Al2O3, or sludge ash-catalyzed pyrolysis of typical 3D printing waste toward tackling plastic pollution.

Catalytic pyrolysis offers a potential solution to tackling plastic pollution by transforming plastic waste into valuable chemicals. This study explored the catalytic pyrolysis of 3D printing waste (3DPW), specifically focusing on photosensitive resin waste (PRW) and polycaprolactone waste (PCLW), with Al2O3, Fe2O3, or sludge ash (SA) containing Fe/Al. The study revealed a synergistic effect between the catalyst and 3DPW, influencing the pyrolysis properties and kinetic models. The addition of Fe2O3 significantly accelerated the main degradation stages, promoting the releases of 2-Ethylacrolein (64.78 % from PRW) and 2-Oxepanone (16.45 % from PCLW), as well as decreasing the acidic products. The catalytic pyrolysis changed the valence state of Fe, with some Fe(III) shifting to Fe(II), accompanied by the release of CO2. The addition of Al2O3 or SA generated new gaseous products (e.g., 2.93 % 1,3-Pentadiene, 2-methyl-, (E)-) through volatile reforming. The joint optimization of the multi-response artificial neural network revealed PCLW/Fe2O3 between 325-399 °C (D = 0.669) as the optimal operation for achieving both minimal remaining mass and maximum decomposition rate. These findings offer actionable insights into the catalytic pyrolysis of 3DPW, promoting its efficient treatment and clean reutilization.

Curcumin activates the Wnt/ß-catenin signaling pathway to alleviate hippocampal neurogenesis abnormalities caused by intermittent hypoxia: A study based on network pharmacology and experimental verification.

The purpose of this work was to investigate how curcumin (Cur) might enhance cognitive function and to gain a better understanding of the molecular mechanisms behind Cur's impacts on neurogenesis deficits brought on by intermittent hypoxia (IH). Using network pharmacology, we explored possible targets for Cur's obstructive sleep apnea (OSA) therapy. We established an IH model using C57BL/6 mice and c17.2 cells, and we assessed the influence of Cur on treatment outcomes as well as the effect of IH on cognitive function. Hippocampal damage and neurogenesis, as well as expression of core targets, were then examined. Network pharmacology analysis revealed that Cur has the potential for multi-target, multi-pathway therapy, with CTNNB1 and MYC as core target genes. The Morris water maze test showed that Cur (100 mg/kg, intragastrically) significantly improved cognitive dysfunction induced by IH. The hematoxylin and eosin (H&E) and Nissl staining indicated that Cur could alleviate damage to the hippocampus caused by IH. Immunohistochemistry, immunofluorescence, and western blotting results showed that Cur might promote neurogenesis and upregulate the expression of ß-catenin and c-myc. In vitro, Cur (0.5 µM) has a protective effect on IH-induced neural stem cells (NSCs) injury and apoptosis and can restore the Wnt/ß-catenin. Cur significantly increased the neurogenesis via the Wnt/ß-catenin pathway, providing the scientific groundwork for the development of new treatment strategies for neurological damage linked to OSA.

Constructing a nomogram to predict overall survival of colon cancer based on computed tomography characteristics and clinicopathological factors.

BACKGROUND: The colon cancer prognosis is influenced by multiple factors, including clinical, pathological, and non-biological factors. However, only a few studies have focused on computed tomography (CT) imaging features. Therefore, this study aims to predict the prognosis of patients with colon cancer by combining CT imaging features with clinical and pathological characteristics, and establishes a nomogram to provide critical guidance for the individualized treatment. AIM: To establish and validate a nomogram to predict the overall survival (OS) of patients with colon cancer. METHODS: A retrospective analysis was conducted on the survival data of 249 patients with colon cancer confirmed by surgical pathology between January 2017 and December 2021. The patients were randomly divided into training and testing groups at a 1:1 ratio. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors associated with OS, and a nomogram model was constructed for the training group. Survival curves were calculated using the Kaplan-Meier method. The concordance index (C-index) and calibration curve were used to evaluate the nomogram model in the training and testing groups. RESULTS: Multivariate logistic regression analysis revealed that lymph node metastasis on CT, perineural invasion, and tumor classification were independent prognostic factors. A nomogram incorporating these variables was constructed, and the C-index of the training and testing groups was 0.804 and 0.692, respectively. The calibration curves demonstrated good consistency between the actual values and predicted probabilities of OS. CONCLUSION: A nomogram combining CT imaging characteristics and clinicopathological factors exhibited good discrimination and reliability. It can aid clinicians in risk stratification and postoperative monitoring and provide important guidance for the individualized treatment of patients with colon cancer.

Recent advances in algorithms predicting hemodynamic instability undergoing surgery for phaeochromocytoma and paraganglioma.

Abdominal pheochromocytomas and paragangliomas (PPGLs) are characterized by the overproduction of catecholamines, which are associated with hemodynamic instability (HDI) during surgery. Therefore, perioperative management to prevent intraoperative HDI is imperative for the surgical treatment of PPGLs. Owing to the rarity and heterogeneous nature of these tumors, pre-surgical prediction of HDI is a clinical dilemma. The reported risk factors for HDI include perioperative preparation, genetic background, tumor conditions, body composition, catecholamine levels, and surgical approach. Additionally, several personalized algorithms or models including these factors have been developed. The first part of this review outlines the prediction models that include clinical features such as tumor size and location, body mass index (BMI), blood glucose level, catecholamine levels, and preoperative management with α-adrenoceptor blockade and crystal/colloid fluid. We then summarize recently reported models that consider additional factors such as genetic background, radiomics, robotic-assisted surgical approach, three-dimensional visualization, and machine-learning models. These findings suggest that a comprehensive model including risk factors is the most likely approach for achieving effective perioperative management.

Dynamics of epitranscriptomes uncover translational reprogramming directed by ac4C in rice during pathogen infection.

Messenger RNA modifications play pivotal roles in RNA biology, but comprehensive landscape changes of epitranscriptomes remain largely unknown in plant immune response. Here we report translational reprogramming directed by ac4C mRNA modification upon pathogen challenge. We first investigate the dynamics of translatomes and epitranscriptomes and uncover that the change in ac4C at single-base resolution promotes translational reprogramming upon Magnaporthe oryzae infection. Then by characterizing the specific distributions of m1A, 2'O-Nm, ac4C, m5C, m6A and m7G, we find that ac4Cs, unlike other modifications, are enriched at the 3rd position of codons, which stabilizes the Watson-Crick base pairing. Importantly, we demonstrate that upon pathogen infection, the increased expression of the ac4C writer OsNAT10/OsACYR (N-ACETYLTRANSFERASE FOR CYTIDINE IN RNA) promotes translation to facilitate rapid activation of immune responses, including the enhancement of jasmonic acid biosynthesis. Our study provides an atlas of mRNA modifications and insights into ac4C function in plant immunity.

GLP-1 analogue liraglutide attenuates CIH-induced cognitive deficits by inhibiting oxidative stress, neuroinflammation, and apoptosis via the Nrf2/HO-1 and MAPK/NF-κB signaling pathways.

Obstructive sleep apnea (OSA) is a common clinical condition linked to cognitive impairment, mainly characterized by chronic intermittent hypoxia (CIH). GLP-1 receptor agonist, known for promoting insulin secretion and reducing glucose levels, has demonstrated neuroprotective effects in various experimental models such as stroke, Alzheimer's disease, and Parkinson's disease. This study aims to investigate the potential role and mechanisms of the GLP-1 receptor agonist liraglutide in ameliorating OSA-induced cognitive deficits. CIH exposure, a well-established and mature OSA pathological model, was used both in vitro and in vivo. In vitro, CIH significantly activated oxidative stress, inflammation, and apoptosis in SH-SY5Y cells. Liraglutide enhanced the nuclear translocation of Nrf2, activating its downstream pathways, thereby mitigating CIH-induced injury in SH-SY5Y cells. Additionally, liraglutide modulated the MAPK/NF-κB signaling pathway, reducing the expression of inflammatory factors and proteins. In vivo, we subjected mice to an intermittent hypoxia incubator to mimic the pathogenesis of human OSA. The Morris water maze test revealed that CIH exposure substantially impaired spatial memory. Subsequent western blot analyses and histopathological examinations indicated that liraglutide could activate the Nrf2/HO-1 axis and inhibit the MAPK/NF-κB signaling pathway, thereby alleviating OSA-associated cognitive dysfunction in mice. These findings suggest that GLP-1 receptor agonists may offer a promising preventive strategy for OSA-associated cognitive impairment. By refining these findings, we provide new insights into GLP-1's protective mechanisms in combating cognitive deficits associated with CIH, underscoring its potential as a therapeutic agent for conditions linked to OSA.

Identification of potent biparatopic antibodies targeting FGFR2 fusion driven cholangiocarcinoma.

Translocations involving FGFR2 gene fusions are common in cholangiocarcinoma and predict response to FGFR kinase inhibitors. However, the rate and durability of response are limited due to the emergence of resistance, typically involving acquired FGFR2 kinase domain mutations, and to sub-optimal dosing, relating to drug adverse effects. Here, we report the development of biparatopic antibodies targeting the FGFR2 extracellular domain (ECD), as candidate therapeutics. Biparatopic antibodies can overcome drawbacks of standard bivalent monoparatopic antibodies, which often show poor inhibitory or even agonist activity against oncogenic receptors. We show that oncogenic transformation by FGFR2 fusions requires an intact ECD. Moreover, by systematically generating biparatopic antibodies that target distinct epitope pairs along the FGFR2 ECD, we identified antibodies that effectively block signaling and malignant growth driven by FGFR2-fusions. Importantly, these antibodies demonstrate efficacy in vivo, synergy with FGFR inhibitors, and activity against FGFR2 fusions harboring kinase domain mutations. Thus, biparatopic antibodies may serve as new treatment options for patients with FGFR2-altered cholangiocarcinoma. Summary: We identify biparatopic FGFR2 antibodies that are effective against FGFR2 fusion driven cholangiocarcinoma.

Giant cell tumor of bone of temporal bone and skull base: report of 6 cases.

OBJECTIVE: Five cases of giant cell tumor of bone (GCTB) in the head and neck region were reported, with a main focus on the radiological findings to identify common characteristics for the diagnosis of GCTB in these sites. MATERIALS AND METHODS: Five consecutive patients diagnosed with GCTB were retrospectively selected. Radiological features on conventional and advanced MR sequences and CT were analyzed. HE staining and immunohistochemical examination were performed using antibodies against p63 and CD68. RESULTS: The common clinical features were local mass (3/5), tinnitus (3/5) and headache (2/5). Radiologically, all the cases were well-circumscribed osteolytic lesion, majority of cases demonstrated an expansile growth pattern and "soap bubble" appearance on CT (4/5). On MRI, the tumors showed predominantly hypointensity both on T1WI and T2WI, and no evidence of restricted diffusion on DWI. Intratumoral hemorrhage (2/5), cystic alternation (2/5) and very low signal on T2WI in the periphery region of the tumor (4/5) was found. Fluid-fluid level was noted in one case, which was eventually verified to be GCTB with secondary aneurysmal bone cyst (ABC). With contrast agent, all the cases showed striking (3/5) or mild to intermediate (2/5) enhancement. CONCLUSIONS: Although the above described radiological findings are not specific for GCTB in head and neck region, a well-defined osteolytic lesion in the bones of head and neck region with "soap bubble" appearance on CT and hypointensity on T2WI with very low signal in the peripheral region of the tumor on MRI highly suggest GCTB for patient ages 20 to 40.

Sleep status of centenarians and its association with death in the China Hainan Centenarian Cohort Study.

OBJECTIVE: This study investigated the associations of sleep status (duration and quality) with all-cause death among centenarians, using data from the China Hainan Centenarians Cohort Study. METHOD: The epidemiological distribution of sleep duration and sleep quality (estimated using the Pittsburgh Sleep Quality Index) was described based on the data from the China Hainan Centenarians Cohort Study. Cox regression was used to analyze the association between sleep status and all-cause mortality. RESULTS: A total of 994 centenarians, with an average age of 102.77 ± 2.75years, were included. The median (Q1, Q3) daytime sleep duration was 1.00 (0.50, 1.50) hour, while nighttime sleep duration and total sleep duration were 8.00 (7.00, 9.00) hours and 9.00 (8.00, 10.50) hours, respectively. By the end of the follow-up period, 517 centenarians had died, with a median follow-up time of 4.2 (1.3-5.0) years. A noteworthy finding emerged: male centenarians with a daytime sleep duration of at least 2 hours had a 97% greater risk of all-cause mortality (HR=1.97, 95%CI: 1.07-3.62, P = .039) than those who got less daytime sleep, after adjusting for potential confounders. CONCLUSION: The sleep duration patterns of centenarians in Hainan were comparable to those in other provinces of China. Centenarians who sleep longer had a higher risk of all-cause mortality. This risk plateaued after more than 9 hours of sleep, with no gender differences observed. Furthermore, the duration of daytime sleep was significantly associated with all-cause mortality among male centenarians.

Structural Heterogeneity of the Rabies Virus Virion.

Rabies virus (RABV) is among the first recognized viruses of public health concern and has historically contributed to the development of viral vaccines. Despite these significances, the three-dimensional structure of the RABV virion remains unknown due to the challenges in isolating structurally homogenous virion samples in sufficient quantities needed for structural investigation. Here, by combining the capabilities of cryogenic electron tomography (cryoET) and microscopy (cryoEM), we determined the three-dimensional structure of the wild-type RABV virion. Tomograms of RABV virions reveal a high level of structural heterogeneity among the bullet-shaped virion particles encompassing the glycoprotein (G) trimer-decorated envelope and the nucleocapsid composed of RNA, nucleoprotein (N), and matrix protein (M). The structure of the trunk region of the virion was determined by cryoEM helical reconstruction, revealing a one-start N-RNA helix bound by a single layer of M proteins at an N:M ratio of 1. The N-M interaction differs from that in fellow rhabdovirus vesicular stomatitis virus (VSV), which features two layers of M stabilizing the N-RNA helix at an M:N ratio of 2. These differences in both M-N stoichiometry and binding allow RABV to flex its N-RNA helix more freely and point to different mechanisms of viral assembly between these two bullet-shaped rhabdoviruses.

Assessment of Endoscopy-Based Scoring Systems for Prognostication in Ulcerative Colitis: A Comparative Analysis.

BACKGROUND AND OBJECTIVE: Endoscopy-based scoring systems, including Mayo Endoscopic Score (MES), Modified Mayo Endoscopic Score (MMES), and Degree of Ulcerative Colitis Burden of Luminal Inflammation (DUBLIN) Score, have been introduced to evaluate UC prognosis. This study aims to compare their predictive capacity for clinical outcomes in UC patients. METHODS: Consecutive UC patients from a tertiary hospital were included. The primary outcome was acute severe ulcerative colitis (ASUC), and secondary outcomes were UC-related admission, medication treatment escalation, disease extension and surgery. Predictive performance was assessed using receiver operating characteristic (ROC) curves. RESULTS: Among 300 patients, 15.3% developed ASUC. Robust correlations were observed among the three scoring systems and were with elevated serum inflammatory markers. The DUBLIN score exhibited superior predictive ability for UC-related admission (AUC 0.751; 95%CI 0.698-0.799) and medication treatment escalation (AUC 0.735; 95% CI 0.681-0.784). No statistical differences were found among three scoring systems for predicting ASUC, disease extension, and surgery. Employing respective cut-offs of 2, 11.25, and 3, higher MES (HR = 3.859, 95% CI 1.636-9.107, p = 0.002), MMES (HR = 3.352, 95% CI 1.879-5.980, p < 0.001), and DUBLIN score (HR = 5.619, 95% CI 2.378-13.277, p < 0.001) were associated with an increased risk of developing ASUC. CONCLUSION: The DUBLIN score, assessing the overall inflammatory burden of the intestinal tract, outperforms the MMES in predicting admission and medication treatment escalation related to UC. Its integration into clinical practice has the potential to enhance risk stratification for patients with UC.