Association of Estimated Glomerular Filtration Rate Trajectories with Atrial Fibrillation Risk in Populations with Normal or Mildly Impaired Renal Function.

Introduction: The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods: This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR <60 mL/min/1.73 m2) before 2010. The eGFR trajectories were developed using latent mixture modeling based on examination data in 2006, 2008, and 2010. Incident AF cases were identified in biennial electrocardiogram assessment and a review of medical insurance data and discharge registers. We used Cox regression models to estimate the hazard ratios and 95% confidence intervals (CIs) for incident AF. Results: According to survey results for the range and changing pattern of eGFR during 2006-2010, four trajectories were identified: high-stable (range, 107.47-110.25 mL/min/1.73 m2; n = 11,719), moderate-increasing (median increase from 83.83 to 100.37 mL/min/1.73 m2; n = 22,634), high-decreasing (median decrease from 101.72 to 89.10 mL/min/1.73 m2; n = 7,943), and low-stable (range, 73.48-76.78 mL/min/1.73 m2; n = 20,111). After an average follow-up of 9.63 years, a total of 485 cases of AF were identified. Compared with the high-stable trajectory, the adjusted hazard ratios of AF were 1.70 (95% CI, 1.09-2.66) for the moderate-increasing trajectory, 1.92 (95% CI, 1.18-3.13) for the high-decreasing trajectory, and 2.28 (95% CI, 1.46-3.56) for the low-stable trajectory. The results remained consistent across a number of sensitivity analyses. Conclusion: The trajectories of eGFR were associated with subsequent AF risk in populations with normal or mildly impaired renal function.

The relation between estimated glomerular filtration rate (eGFR) within the normal or mildly impaired range and risk of atrial fibrillation (AF) in former studies is controversial, and data on longitudinal pattern of eGFR in such topic is sparse. In this cohort study, we identified 4 trajectories of eGFR in populations with normal or mildly impaired renal function. Relative to populations with high-stable pattern of eGFR, those with low-stable pattern, high-decreasing pattern and moderate-increasing pattern were associated with 128%, 92%, and 70% higher risk of AF, respectively. These findings suggested that monitoring eGFR trajectories is an important approach for AF prediction in populations with normal or mildly impaired renal function. Decreasing and consistently low eGFR trajectories within the currently designated normal or mildly impaired range may still significantly increase the risk of AF.

Deep machine learning identified fish flesh using multispectral imaging.

Food fraud is widespread in the aquatic food market, hence fast and non-destructive methods of identification of fish flesh are needed. In this study, multispectral imaging (MSI) was used to screen flesh slices from 20 edible fish species commonly found in the sea around Yantai, China, by combining identification based on the mitochondrial COI gene. We found that nCDA images transformed from MSI data showed significant differences in flesh splices of the 20 fish species. We then employed eight models to compare their prediction performances based on the hold-out method with 70% training and 30% test sets. Convolutional neural network (CNN), quadratic discriminant analysis (QDA), support vector machine (SVM), and linear discriminant analysis (LDA) models perform well on cross-validation and test data. CNN and QDA achieved more than 99% accuracy on the test set. By extracting the CNN features for optimization, a very high degree of separation was obtained for all species. Furthermore, based on the Gini index in RF, 11 bands were selected as key classification features for CNN, and an accuracy of 98% was achieved. Our study developed a successful pipeline for employing machine learning models (especially CNN) on MSI identification of fish flesh, and provided a convenient and non-destructive method to determine the marketing of fish flesh in the future.

Deciphering the Biological Aging Impact on Alveolar Bone Loss: Insights From α-Klotho and Renal Function Dynamics.

Alveolar bone loss is generally considered a chronological age-related disease. As biological aging process is not absolutely determined by increasing age, whether alveolar bone loss is associated with increasing chronological age or biological aging remains unclear. Accurately distinguishing whether alveolar bone loss is chronological age-related or biological aging-related is critical for selecting appropriate clinical treatments. This study aimed to identify the relationship between alveolar bone loss and body aging. In total, 3 635 participants from the National Health and Nutrition Examination Survey and 71 living kidney transplant recipients from Gene Expression Omnibus Datasets were enrolled. Multivariate regression analysis, smooth curve fittings, and generalized additive models were used to explore the association among alveolar bone loss, age, serum α-Klotho level, renal function markers, as well as between preoperative creatinine and renal cortex-related α-Klotho gene expression level. Meanwhile, a 2-sample Mendelian randomization (MR) study was conducted to assess the causal relationship between α-Klotho and periodontal disease (4 376 individuals vs 361 194 individuals). As a biological aging-related indicator, the α-Klotho level was negatively correlated with impaired renal function and alveolar bone loss. Correspondingly, accompanied by decreasing renal function, it was manifested with a downregulated expression level of α-Klotho in the renal cortex and aggravated alveolar bone loss. The MR analysis further identified the negative association between higher genetically predicted α-Klotho concentrations with alveolar bone loss susceptibility using the IVW (odds ratio [OR] = 0.999, p = .005). However, an inversely U-shaped association was observed between chronological age and alveolar bone loss, which is especially stable in men (the optimal cutoff values were both 62 years old). For men above 62 years old, increasing age is converted to protective factor and is accompanied by alleviated alveolar bone loss. Alveolar bone loss that is directly associated with decreased renal function and α-Klotho level was related to biological aging rather than chronological age. The renal-alveolar bone axis could provide a new sight of clinical therapy in alveolar bone loss.

Cerium Vanadate Nanozyme with pH-Dependent Dual Enzymatic Activity for Glioblastoma Targeted Therapy and Postradiotherapy Damage Protection.

Nanocatalytic therapy is an emerging technology that uses synthetic nanoscale enzyme mimics for biomedical treatment. However, in the field of neuroscience, achieving neurological protection while simultaneously killing tumor cells is a technical challenge. Herein, we synthesized a biomimic and translational cerium vanadate (CeVO4) nanozyme for glioblastoma (GBM) therapy and the repair of brain damage after GBM ionizing radiation (IR). This system exhibited pH dependence: it showed potent Superoxide dismutase (SOD) enzyme activity in a neutral environment and Peroxidase (POD) enzyme activity in an acidic environment. In GBM cells, this system acted in lysosomes, causing cellular damage and reactive oxygen species (ROS) accumulation; in neuronal cells, this nanozyme could undergo lysosomal escape and nanozyme aggregation with mitochondria, reversing the mitochondrial damage caused by IR and restoring the expression level of the antiapoptotic BCL-2 protein. Mechanistically, we believe that this distribution difference is related to the specific uptake internalization mechanism and lysosomal repair pathway in neurons, and ultimately led to the dual effect of tumor killing and nerve repair in the in vivo model. In summary, this study provides insight into the repair of brain damage after GBM radiation therapy.

A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.

The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.

Ecological restoration for eutrophication mitigation in urban interconnected water bodies: Evaluation, variability and strategy.

Many urban water bodies grapple with low flow flux and weak hydrodynamics. To address these issues, projects have been implemented to form integrated urban water bodies via interconnecting artificial lake or ponds with rivers, but causing pollution accumulation downstream and eutrophication. Despite it is crucial to assess eutrophication, research on this topic in urban interconnected water bodies is limited, particularly regarding variability and feasible strategies for remediation. This study focused on the Loucun river in Shenzhen, comprising an pond, river and artificial lake, evaluating water quality changes pre-(post-)ecological remediation and establishing a new method for evaluating the water quality index (WQI). The underwater forest project, involving basement improvement, vegetation restoration, and aquatic augmentation, in the artificial lake significantly reduced total nitrogen (by 43.58%), total phosphorus (by 79.17%) and algae density (by 36.90%) compared to pre-remediation, effectively controlling algal bloom. Rainfall, acting as a variable factor, exacerbated downstream nutrient accumulation, increasing total phosphorus by 4.56 times and ammonia nitrogen by 1.30 times compared to the dry season, and leading to algal blooms in the non-restoration pond. The improved WQI method effectively assesses water quality status. The interconnected water body exhibits obvious nutrient accumulation in downstream regions. A combined strategy that reducing nutrient and augmenting flux was verified to alleviate accumulation of nutrients downstream. This study provides valuable insights into pollution management strategies for interconnected pond-river-lake water bodies, offering significant reference for nutrient mitigation in such urban water bodies.

Intraoperative rapid molecular diagnosis aids glioma subtyping and guides precise surgical resection.

OBJECTIVE: The molecular era of glioma diagnosis and treatment has arrived, and a single rapid histopathology is no longer sufficient for surgery. This study sought to present an automatic integrated gene detection system (AIGS), which enables rapid intraoperative detection of IDH/TERTp mutations. METHODS: A total of 78 patients with gliomas were included in this study. IDH/TERTp mutations were detected intraoperatively using AIGS in 41 of these patients, and they were guided to surgical resection (AIGS detection group). The remaining 37 underwent histopathology-guided conventional surgical resection (non-AIGS detection group). The clinical utility of this technique was evaluated by comparing the accuracy of glioma subtype diagnosis before and after TERTp mutation results were obtained by pathologists and the extent of resection (EOR) and patient prognosis for molecular pathology-guided glioma surgery. RESULTS: With NGS/Sanger sequencing and chromosome detection as the gold standard, the accuracy of AIGS results was 100%. And the timing was well matched to the intraoperative rapid pathology report. After obtaining the TERTp mutation detection results, the accuracy of the glioma subtype diagnosis made by the pathologists increased by 19.51%. Molecular pathology-guided surgical resection of gliomas significantly increased EOR (99.06% vs. 93.73%, p < 0.0001) and also improved median OS (26.77 vs. 13.47 months, p = 0.0289) and median PFS (15.90 vs. 10.57 months, p = 0.0181) in patients with glioblastoma. INTERPRETATION: Using AIGS intraoperatively to detect IDH/TERTp mutations to accurately diagnose glioma subtypes can help achieve maximum safe resection of gliomas, which in turn improves the survival prognosis of patients.

Whether weekend warriors (WWs) achieve equivalent benefits in lipid accumulation products (LAP) reduction as other leisure-time physical activity patterns? -Results from a population-based analysis of NHANES 2007-2018.

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.

Fangyukangsuan granules ameliorate hyperuricemia and modulate gut microbiota in rats.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

Toxicity threshold and ecological risk of nitrate in rivers based on endocrine-disrupting effects: A case study in the Luan River basin, China.

Nitrate, as a crucial nutrient, is consistently targeted for controlling water eutrophication globally. However, there is considerable evidence suggesting that nitrate has endocrine-disrupting potential on aquatic organisms. In this study, the sensitivity of various adverse effects to nitrate nitrogen (nitrate-N) was compared, and a toxicity threshold based on endocrine-disrupting effects was derived. The spatiotemporal variations of nitrate-N concentrations in the Luan River basin were investigated, and the associated aquatic ecological risks were evaluated using a comprehensive approach. The results showed that reproduction and development were the most sensitive endpoints to nitrate, and their distribution exhibited significant differences compared to behavior. The derived threshold based on endocrine-disrupting effects was 0.65 mgL-1, providing adequate protection for the aquatic ecosystem. In the Luan River basin, the mean nitrate-N concentrations during winter (4.4 mgL-1) were significantly higher than those observed in spring (0.7 mgL-1) and summer (1.2 mgL-1). Tributary inputs had an important influence on the spatial characteristics of nitrate-N in the mainstream, primarily due to agricultural and population-related contamination. The risk quotients (RQ) during winter, summer, and spring were evaluated as 6.7, 1.8, and 1.1, respectively, and the frequency of exposure concentrations exceeding the threshold was 100 %, 64.3 %, and 42.5 %, respectively. At the ecosystem level, nitrate posed intermediate risks to aquatic organisms during winter and summer in the Luan River basin and at the national scale in China. We suggest that nitrate pollution control should not solely focus on water eutrophication but also consider the endocrine disruptive effect on aquatic animals.

Cell wall-mediated root development is targeted by a soil-borne bacterial pathogen to promote infection.

Plant pathogens manipulate host development, facilitating colonization and proliferation. Ralstonia solanacearum is a soil-borne bacterial pathogen that penetrates roots and colonizes plants through the vascular system, causing wilting and death. Here, we find that RipAC, an effector protein from R. solanacearum, alters root development in Arabidopsis, promoting the formation of lateral roots and root hairs. RipAC interacts with CELLULOSE SYNTHASE (CESA)-INTERACTIVE PROTEIN 1 (CSI1), which regulates the activity of CESA complexes at the plasma membrane. RipAC disrupts CESA-CSI1 interaction, leading to a reduction in cellulose content, root developmental alterations, and a promotion of bacterial pathogenicity. We find that CSI1 also associates with the receptor kinase FERONIA, forming a complex that negatively regulates immunity in roots; this interaction, however, is not affected by RipAC. Our work reveals a bacterial virulence strategy that selectively affects the activities of a host target, promoting anatomical alterations that facilitate infection without causing activation of immunity.

One-Stone-for-Two-Birds Method to Improve the SnO2 Layers for High Power-per-Weight Flexible Perovskite Solar Cell Mini-modules.

Maintaining the power conversion efficiency (PCE) of flexible perovskite solar cells (fPSCs) while decreasing their weight is essential to utilize their lightweight and flexibility as much as possible for commercialization. Strengthening the interfaces between functional layers, such as flexible substrates, charge transport layers, and perovskite active layers, is critical to addressing the issue. Herein, we propose a feasible and one-stone-for-two-birds method to improve the electron transport layer (ETL), SnO2, and the interface between the ETL and perovskite layer simultaneously. In detail, poly(acrylate ammonium) (PAAm), a low-cost polymer with a long chain structure, is added into the SnO2 aqueous solution to reduce the aggregation of SnO2 nanoparticles, resulting in the deposition of a conformal and high-quality ETL film on the tin-doped indium oxide film surface. Simultaneously, PAAm addition can effectively regulate the crystallization of the perovskite films, strengthening the interface between the SnO2 film and the buried surface of the perovskite layer. The outstanding PCEs of 22.41% on small-scale fPSCs and 18.54% on fPSC mini-modules are among the state-of-the-art n-i-p type fPSCs. Moreover, the fPSC mini-module on the 20 µm-thick flexible substrate shows a comparable PCE with that of the fPSC mini-module on the 125 µm-thick flexible substrate, exhibiting a high power-to-weight of 5.097 W/g. This work provides an easy but essential direction for further applications of fPSCs in diverse scenarios.

The Numerical Simulations and Experimental Study of an 8-Inch SiC Single Crystal with Reduced BPD Density.

The basal plane dislocation (BPD) density is one of the most important defects affecting the application of SiC wafers. In this study, numerical simulations and corresponding experiments were conducted to investigate the influence of cooling processes, seed-bonding methods, and graphite crucible materials on the BPD density in an 8-inch N-type 4H-SiC single crystal grown by the physical vapor transport (PVT) method. The results showed that the BPD density could be effectively reduced by increasing the cooling rate, optimizing the seed-bonding method, and adopting a graphite crucible with a similar coefficient of thermal expansion as the SiC single crystal. The BPD density in the experiments showed that a high cooling rate reduced the BPD density from 4689 cm-2 to 2925 cm-2; optimization of the seed-bonding method decreased the BPD density to 1560 cm-2. The BPD density was further reduced to 704 cm-2 through the adoption of a graphite crucible with a smaller thermal expansion coefficient.

An improved technology for monitoring groundwater flow velocity and direction in fractured rock system based on colloidal particles motion.

The colloidal borescope, using colloidal particle motion, is used to monitor the flow velocities and directions of groundwater. It integrates advanced techniques such as microscopy, high-speed photography, and big data computing and enjoys high sensitivity at the micron level. However, In the same well, the groundwater flow velocity monitored by colloidal hole mirror is varies greatly from that obtained by conventional hydrogeological monitoring, such as pumping test. In order to solve this problem, the stability catcher and stratified packer are designed to control the interference of the vertical flow in drilling, and to monitor the flow velocity and direction of groundwater velocity at the target aquifer and target fracture. Five wells with different aquifers and different groundwater types were selected for monitoring in south-central China. The instantaneous velocity and direction are converted into east-west component and north-south component, the average velocity and direction is calculated according to the time of 10 min, and the particle trajectory diagram is established. Based on these results, it proposed a concept of cumulative flow velocity. Using curve-fitting equations, the limits of cumulative flow velocities as the monitoring time tends to infinity were then calculated as the actual flow velocities of the groundwater. The permeability coefficient of aquifer is calculated by using the fissure ratio of aquifer, hydraulic slope and flow velocity, and compared with the permeability coefficient obtained by pumping test. The results are as follows: (1) The variation coefficient of the instantaneous flow velocity measured at the same depth in the same well at different times is greater than that of the time average flow velocity and greater than that of the cumulative flow velocity. The variation coefficient of the actual velocity is the smallest, indicating that the risk of using the actual flow velocity is lower. (2) The variation coefficient of the flow rate monitored at different depths in the same well is mainly controlled by the properties of the aquifer. The more uniform water storage space in the aquifer, the smaller the variation coefficient. (3) The comparison between the permeability coefficient obtained by monitoring and the permeability coefficient obtained by pumping test shows that the flow of structural fissure water controlled by planar fissure is more surface flow, and the results are consistent. When the groundwater flow is controlled by pores and solution gaps, the flow channel is complicated, which is easy to produce turbulent flow, and the result consistency is poor. (4) According to different research accuracy requirements, different monitoring and calculation methods can be selected for different aquifers and groundwater types. Researches show that, the permeability coefficient calculated for the actual flow velocity in well DR01 is the same as that calculated for the pumping test. The aquifer characteristics reflected by the coefficient of variation of the actual flow velocity in the same aquifer are more realistic. The pumping test method obtains the comprehensive parameters of a certain aquifer, and this method can be used to monitor a certain fissure. In this paper, the new technology developed for monitoring, and the new algorithm established for data processing, can accurately obtain the flow velocity and direction of groundwater, using capsule hole mirror monitoring method. The key parameters of hydrogeology can be obtained by using one well, which can reduce the time and cost input and improve the work efficiency.

The association between different physical activity (PA) patterns and cardiometabolic index (CMI) in US adult population from NHANES (2007-2016).

Background: Physical activity (PA) is widely recommended for preventing and combating obesity, but the most effective PA pattern for treating obesity remains unclear. Cardiometabolic index (CMI), derived from waist height ratio and triglycerides to high-density lipoprotein-cholesterol ratio, is a novel indicator for evaluating obesity. However, the relationship between different PA patterns and CMI remains unelucidated. Objective: This study aimed to explore the association between different PA patterns and CMI in U.S. adults. Methods: Participants with complete information in CMI, PA patterns, and other covariates in the National Health and Nutrition Examination Survey database (2007-2016) were included in this study. Multivariate linear regression models were utilized to explore the relationship between PA patterns and CMI. Moreover, stratified analyses, interaction tests and restricted cubic spline (RCS) regression analysis were used to investigate the stability and nonlinearity of the association, respectively. Results: A total of 16,442 adults were included in this study. After adjusting for all potential covariates, only the regularly active group was significantly associated with CMI reduction (ß = -0.13, 95% CI: 0.19 to -0.07, P < 0.0001), while the weekend warriors group did not achieve equivalent CMI reduction (ß = -0.09, 95% CI: 0.32 to 0.14, P = 0.4204). Subgroup analyses and interaction tests revealed that the CMI-PA association was more pronounced in the subgroup with age≤45 or >60, with higher education level, and who are current drinkers. Furthermore, RCS analysis indicated that total PA in a week was significantly, nonlinearly associated with CMI in non-inactive adults, and that a total of PA more than 330 min can reap favorable CMI reduction. Conclusion: Being regularly active is associated with significant CMI reduction, while being weekend warriors and insufficiently active do not achieve equivalent benefits. For non-inactive individuals, engaging in PA for more than 330 min weekly helps to reduce CMI effectively.

Efficient EVs separation and detection by an alumina-nanochannel-array-membrane integrated microfluidic chip and an antibody barcode biochip.

BACKGROUND: Small endosome-derived lipid nanovesicles (30-200 nm) are actively secreted by living cells and serve as pivotal biomarkers for early cancer diagnosis. However, the study of extracellular vesicles (EVs) requires isolation and purification from various body fluids. Although traditional EVs isolation and detection technologies are mature, they usually require large amount of sample, consumes long-time, and have relatively low-throughput. How to efficiently isolate, purify and detect these structurally specific EVs from body fluids with high-throughput remains a great challenge in in vitro diagnostics and clinical research. RESULTS: Herein, we suggest a nanosized microfluidic device for efficient and economical EVs filtration based on an alumina nanochannel array membrane. We evaluated the filtration device performance of alumina membranes with different diameters and found that an optimized chamber array with a hydrophilic-treated channel diameter of 90 nm could realize a filtration efficiency of up to 82% without any assistance from chemical or physical separation methods. Importantly, by integrating meticulously designed multichannel microfluidic biochips, EVs can be captured in-situ and monitored by antibody barcode biochip. The proposed filtration chip together with the high-throughput detection chip were capable of filtration of a few tens of µL samples and recognition of different phonotypes. The practical filtration and detection of EVs from clinical samples demonstrated the high performance of the device. SIGNIFICANT: Overall, this work provides a cost-effective, highly efficient and automated EVs filtration chip and detection dual-function integrated chip platform, which can directly separate EVs from serum or cerebrospinal fluid with an efficiency of 82% and conduct in-situ detection. This small fluidic device can provide a powerful tool for highly efficient identifying and analyzing EVs, presenting great application potential in clinical detection.

Combined effect of time in target range and variability of systolic blood pressure on cardiovascular outcomes and mortality in patients with hypertension: A prospective cohort study.

Time in target range (TTR) and blood pressure variability (BPV) of systolic blood pressure (SBP) are independent risk factors for major adverse cardiovascular events (MACE) and all-cause mortality in hypertensive patients. However, the association of the combination of low TTR and high BPV of SBP with the risk of MACE and all-cause mortality is unclear. This study sought to investigate the combined effect of the TTR and BPV on the risk of MACE and all-cause mortality in patients with hypertension. A total of 11 496 hypertensive patients from the Kailuan cohort study were included in our study. All participants were divided into four groups according to their TTR and BPV levels. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident MACE and all-cause mortality. During a median follow-up of 5.64 years, 839 MACEs (included 99 cases of myocardial infarction, 591 cases of stroke, and 191 cases of heart failure) and 621 deaths occurred. Compared with the high-TTR and low-BPV group, the HRs (95% CI) of MACE and all-cause mortality were 1.309 (1.025-1.671) and 1.842 (1.373-2.473) for the high-TTR and high-BPV group, 1.692 (1.347-2.125) and 1.731 (1.298-2.309) for the low-TTR & low-BPV group, 2.132 (1.728-2.629) and 2.247 (1.722-2.932) for the low-TTR & high-BPV group. Our study suggests that the combination of low TTR and high BPV of SBP was associated with a higher risk of MACE and all-cause mortality in patients with hypertension.

Investigation of Multi-Factor Stress Corrosion Cracking Failure of Safe-End Feedwater Lines of Submarine Power System.

The corrosion process under the complex safe-end feedwater line conditions was investigated via experimental lab testing and numerical simulation. The corrosion of safe-end feedwater lines was controlled through the combination of galvanic corrosion, residual stress, and flow velocity. Firstly, galvanic corrosion occurred once the 20 steel was welded with 316L stainless steel. The pitting corrosion could be observed on the 20 steel side of the weld joint. Secondly, a vortex flow was detected around the welding bump and within the pits. The growth of the pits was accelerated in both the vertical and horizontal directions. Finally, under the residual stress condition, the stress intensity factor (K) at the bottom of the pits was easier to reach than the critical stress intensity factor (KISCC). Then, pitting was transformed into stress corrosion cracking which then propagated along the weld line. Therefore, the critical factor inducing the failure of safe-end feedwater lines was the combined action of galvanic corrosion, residual stress, and flow velocity.

Premature coronary heart disease complicated with hypertension in hospitalized patients: Incidence, risk factors, cardiovascular-related comorbidities and prognosis, 2008-2018.

Background: The clinical characteristics and risk factors of all-cause mortality in young hospitalized patients with comorbid coronary heart disease and hypertension (CAD + HT) are not well-characterized. Method: A total of 2288 hospitalized CAD patients (age<45 years) with or without hypertension in the Chinese PLA General Hospital from August 5, 2008 to June 22, 2018 were conducted. The risk factors of all-cause mortality were estimated in young CAD + HT patients by COX models. Results: The overall prevalence of hypertension in young CAD patients was 50.83% (n = 1163). CAD + HT patients had older age, higher heart rate, BMI, uric acid, triglyceride and lower level of eGFR and HDL-C than CAD patients (P < 0.05). The proportion of cardiovascular-related comorbidities (including obesity, diabetes mellitus, hyperuricemia and chronic kidney disease [CKD]) in the CAD + HT group was significantly higher than that in CAD group (P < 0.0001). The risk of all-cause mortality was higher in CAD + HT patients, although after adjusting for all covariates, there was no significant difference between the two groups. Furthermore, CKD (HR, 3.662; 95% CI, 1.545-8.682) and heart failure (HF) (HR, 3.136; 95%CI, 1.276-7.703) were associated with an increased risk of all-cause mortality and RAASi (HR, 0.378; 95%CI, 0.174-0.819) had a beneficial impact in CAD + HT patients. Conclusions: Hypertension was highly prevalent in young CAD patients. Young CAD + HT patients had more cardiovascular metabolic risk factors, more cardiovascular-related comorbidities and higher risk of all-cause mortality. CKD and HF were the risk factors, while RAASi was a protective factor, of all-cause mortality in CAD + HT patients.

Disulfidptosis features and prognosis in head and neck squamous cell carcinoma patients: unveiling and validating the prognostic signature across cohorts.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a significant health concern with a variable global incidence and is linked to regional lifestyle factors and HPV infections. Despite treatment advances, patient prognosis remains variable, necessitating an understanding of its molecular mechanisms and the identification of reliable prognostic biomarkers. METHODS: We analyzed 959 HNSCC samples and employed batch correction to obtain consistent transcriptomic data across cohorts. We examined 79 disulfidptosis-related genes to determine consensus clusters and utilized high-throughput sequencing to identify genetic heterogeneity within tumors. We established a disulfidptosis prognostic signature (DSPS) using least absolute shrinkage and selection operator (LASSO) regression and developed a prognostic nomogram integrating the DSPS with clinical factors. Personalized chemotherapy prediction was performed using the "pRRophetic" R package. RESULTS: Batch corrections were used to harmonize gene expression data, revealing two distinct disulfidptosis subtypes, C1 and C2, with differential gene expression and survival outcomes. Subtype C1, characterized by increased expression of the MYH family genes ACTB, ACTN2, and FLNC, had a mortality rate of 48.4%, while subtype C2 had a mortality rate of 38.7% (HR = 0.77, 95% CI: 0.633-0.934, P = 0.008). LASSO regression identified 15 genes that composed the DSPS prognostic model, which independently predicted survival (HR = 2.055, 95% CI: 1.420-2.975, P < 0.001). The prognostic nomogram, which included the DSPS, age, and tumor stage, predicted survival with AUC values of 0.686, 0.704, and 0.789 at 3, 5, and 8 years, respectively, indicating strong predictive capability. In the external validation cohort (cohort B), the DSPS successfully identified patients at greater risk, with worse overall survival outcomes in the high-DSPS subgroup (HR = 1.54, 95% CI: 1.17-2.023, P = 0.002) and AUC values of 0.601, 0.644, 0.636, and 0.748 at 3, 5, 8, and 10 years, respectively, confirming the model's robustness. CONCLUSION: The DSPS provides a robust prognostic tool for HNSCC, underscoring the complexity of this disease and the potential for tailored treatment strategies. This study highlights the importance of molecular signatures in oncology, offering a step toward personalized medicine and improved patient outcomes in HNSCC management.