Search

Non-communicable diseases (NCDs), including cardiovascular diseases, cancer, metabolic diseases, and skeletal diseases, pose significant challenges to public health worldwide. The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage. Nuclear factor erythroid 2-related factor 2 (Nrf2), a critical transcription factor, plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury. Therefore, Nrf2-targeting therapies hold promise for preventing and treating NCDs. Quercetin (Que) is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties. It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation. Que modulates mitochondrial function, apoptosis, autophagy, and cell damage biomarkers to regulate oxidative stress and inflammation, highlighting its efficacy as a therapeutic agent against NCDs. Here, we discussed, for the first time, the close association between NCD pathogenesis and the Nrf2 signaling pathway, involved in neurodegenerative diseases (NDDs), cardiovascular disease, cancers, organ damage, and bone damage. Furthermore, we reviewed the availability, pharmacokinetics, pharmaceutics, and therapeutic applications of Que in treating NCDs. In addition, we focused on the challenges and prospects for its clinical use. Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

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

To explore the effect of postharvest dehydration on grape berries and wine quality, we determined physicochemical properties, polyphenols, antioxidant activities, volatile compounds and sensory characteristics for wines brewed by ‘Marselan’ (Vitis vinifera L.) grapes with 0%, 10%, 15%, 20%, and 25% of water loss. The result showed that postharvest dehydration improved the alcohol content, residual sugar and titratable acidity of Marselan wine. Phenolic compounds and antioxidant activities in wines with a dehydration of 20% have significantly increased. Postharvest dehydration increased the contents of isobutanol, isoamyl alcohol, phenylethyl alcohol, ethyl acetate, isoamyl acetate and ethyl butyrate in Marselan wines, and enhanced the floral, fruity and sweet taste of wines. Marselan wine had the lowest acceptability score under the condition of severe dehydration (25% dehydration), which was related to the significant increase of tannins content. In summary, postharvest dehydration was beneficial in improving the quality of Marselan wine.

Abstract Perovskite single crystals have attracted tremendous attention owing to their excellent optoelectronic properties and stability compared to typical multicrystal structures. However, the growth of high‐quality perovskite single crystals (PSCs) generally relies on temperature gradients or the introduction of additives to promote crystal growth. In this study, a vacuum evaporation crystallization technique is developed that allows PSCs to be grown under extremely stable conditions at constant temperature and without requiring additives to promote crystal growth. The new method enables the growth of PSCs of unprecedented quality, that is, MAPbBr3 single crystals that exhibit an ultranarrow full width at half maximum of 0.00701°, which surpasses that of all previously reported values. In addition, the MAPbBr3 single crystals deliver exceptional optoelectronic performance, including a long carrier lifetime of 1006 ns, an ultralow trap‐state density of 3.67 × 109 cm−3, and an ultrahigh carrier mobility of 185.86 cm2 V−1 s−1. This method is applicable to various types of PSCs, including organic–inorganic hybrids, fully inorganic structures, and low‐dimensional structures.

Deformation control of deep roadways is a major challenge for mine safety production. Taking a deep roadway with a burial depth of 965 m in a mine in North China as the engineering background, on-site investigation found that significant creep deformation occurred in the surrounding rock of the roadway. The original supporting U-shaped steel support failed due to insufficient supporting strength. The rock mass near the roadway experienced a transition from triaxial stress conditions to biaxial and even uniaxial stress states as a result of excavation and unloading, leading to a gradient stress distribution in the surrounding rock. From the perspective of the roadway's deviatoric stress field distribution, we investigated the gradient failure mechanism of the roadway and validated it through theoretical analysis and numerical simulations. The study found that the ratio of horizontal principal stress and vertical principal stress determines the distribution shape of the surrounding rock deviatoric stress field. The gradient distribution of the stress field in the roadway will cause time-related deformation of the roadway, which will lead to large deformation and failure of the roadway. Based on this, the control mechanism of roadway gradient failure was studied, and then a combined support technology of CFST supports with high bearing capacity was proposed.

Diabetic cardiomyopathy (DCM) is a cardiac microvascular complication caused by metabolic disorders. It is characterized by myocardial remodeling and dysfunction. The pathogenesis of DCM is associated with abnormal cellular metabolism and organelle accumulation. Autophagy is thought to play a key role in the diabetic heart, and a growing body of research suggests that modulating autophagy may be a potential therapeutic strategy for DCM. Here, we have summarized the major signaling pathways involved in the regulation of autophagy in DCM, including Adenosine 5’-monophosphate-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), Forkhead box subfamily O proteins (FOXOs), Sirtuins (SIRTs), and PTEN-inducible kinase 1 (PINK1)/Parkin. Given the significant role of autophagy in DCM, we further identified natural products and chemical drugs as regulators of autophagy in the treatment of DCM. This review may help to better understand the autophagy mechanism of drugs for DCM and promote their clinical application.

To address the issues of heat and humidity hazards, as well as insufficient air volume in deep mining operations, a novel cooling method combining spray and chord grid is proposed. To investigate the cooling dynamics, an experimental platform integrating both spray and chord grid components is independently developed. Field boundary conditions are simulated to conduct orthogonal experimental research. Under the experimental parameters of an inlet air temperature of 32 °C, relative humidity of 88 %, and initial spray water temperature of 26 °C, the effects of water-air ratio, nozzle distance, and other parameters on inlet and outlet temperature, as well as moisture content, are quantified. These influencing factors are analyzed through range analysis. Results demonstrate that the water-air ratio has a greater impact on cooling compared to the nozzle distance. Notably, when the water-air ratio and nozzle distance reach critical values of 0.6 and 70 cm respectively, the cooling rate begins to plateau. Furthermore, comparative analysis of the cooling and dehumidification effects of single spray versus spray + chord grid reveals that the cooling capacity of single spray systems can be surpassed by incorporating a chord grid. Specifically, the combination of spray + chord grid achieves superior cooling effects with lower water consumption.

Objectives: This study aims to assess the efficacy of narrow band imaging (NBI) endoscopy in utilizing radiomics for predicting radiosensitivity in nasopharyngeal carcinoma (NPC), and to explore the associated molecular mechanisms. Materials: The study included 57 NPC patients who were pathologically diagnosed and underwent RNA sequencing. They were categorized into complete response (CR) and partial response (PR) groups after receiving radical concurrent chemoradiotherapy. We analyzed 267 NBI images using ResNet50 for feature extraction, obtaining 2048 radiomic features per image. Using Python for deep learning and least absolute shrinkage and selection operator for feature selection, we identified differentially expressed genes associated with radiomic features. Subsequently, we conducted enrichment analysis on these genes and validated their roles in the tumor immune microenvironment through single-cell RNA sequencing. Results: After feature selection, 54 radiomic features were obtained. The machine learning algorithm constructed from these features showed that the random forest algorithm had the highest average accuracy rate of 0.909 and an area under the curve of 0.961. Correlation analysis identified 30 differential genes most closely associated with the radiomic features. Enrichment and immune infiltration analysis indicated that tumor-associated macrophages are closely related to treatment responses. Three key NBI differentially expressed immune genes (NBI-DEIGs), namely CCL8, SLC11A1, and PTGS2, were identified as regulators influencing treatment responses through macrophages. Conclusion: NBI-based radiomics models introduce a novel and effective method for predicting radiosensitivity in NPC. The molecular mechanisms may involve the functional states of macrophages, as reflected by key regulatory genes.

Background: The present study aimed to develop and validate a prediction nomogram model for 5-year all-cause mortality in diabetic patients with hypertension. Methods: Data were extracted from the National Health and Nutrition Examination Survey (NHANES). A total of 3291 diabetic patients with hypertension in the NHANES cycles for 1999–2014 were selected and randomly assigned at a ratio of 8:2 to the training cohort (n = 2633) and validation cohort (n = 658). Multivariable Cox regression was conducted to establish a visual nomogram model for predicting the risk of 5-year all-cause mortality. Receiver operating characteristic curves and C-indexes were used to evaluate the discriminant ability of the prediction nomogram model for all-cause mortality. Survival curves were created using the Kaplan–Meier method and compared by the log-rank test. Results: The nomogram model included eight independent predictors: age, sex, education status, marital status, smoking, serum albumin, blood urea nitrogen, and previous cardiovascular disease. The C-indexes for the model in the training and validation cohorts were 0.76 (95% confidence interval: 0.73–0.79, p

Abstract Cirrus clouds often contain numerous hollow ice crystals, which are distinct in scattering properties from solid ice crystals, and will be challenging to microphysical retrieval and radiative forcing assessment. Currently, hollow ice crystals have not been observed by remote sensing methods, and the estimation of their hollowness is a complex task. To address this issue, the Mixed Modal Hollow Columns (MMHC) model for hollow ice crystals is introduced, and its backscattering properties are computed using the physical optics approximation method. Through comparison with spaceborne lidar observations, we identify a specific type of cirrus associated with the MMHC model for the first time. The visible optical depth of this cirrus is less than or equal to 0.1, and the temperature is between −60 and −40°C. The MMHC characteristic cirrus clouds are prevalent in middle and high latitudes but less common in low latitudes. They exhibit distinct patterns in terms of sea and land distribution as well as seasonal variation.

ObjectiveThis study focuses on enhancing the precision of epidemic time series data prediction by integrating Gated Recurrent Unit (GRU) into a Graph Neural Network (GNN), forming the GRGNN. The accuracy of the GNN (Graph Neural Network) network with introduced GRU (Gated Recurrent Units) is validated by comparing it with seven commonly used prediction methods.MethodThe GRGNN methodology involves multivariate time series prediction using a GNN (Graph Neural Network) network improved by the integration of GRU (Gated Recurrent Units). Additionally, Graphical Fourier Transform (GFT) and Discrete Fourier Transform (DFT) are introduced. GFT captures inter-sequence correlations in the spectral domain, while DFT transforms data from the time domain to the frequency domain, revealing temporal node correlations. Following GFT and DFT, outbreak data are predicted through one-dimensional convolution and gated linear regression in the frequency domain, graph convolution in the spectral domain, and GRU (Gated Recurrent Units) in the time domain. The inverse transformation of GFT and DFT is employed, and final predictions are obtained after passing through a fully connected layer. Evaluation is conducted on three datasets: the COVID-19 datasets of 38 African countries and 42 European countries from worldometers, and the chickenpox dataset of 20 Hungarian regions from Kaggle. Metrics include Average Root Mean Square Error (ARMSE) and Average Mean Absolute Error (AMAE).ResultFor African COVID-19 dataset and Hungarian Chickenpox dataset, GRGNN consistently outperforms other methods in ARMSE and AMAE across various prediction step lengths. Optimal results are achieved even at extended prediction steps, highlighting the model’s robustness.ConclusionGRGNN proves effective in predicting epidemic time series data with high accuracy, demonstrating its potential in epidemic surveillance and early warning applications. However, further discussions and studies are warranted to refine its application and judgment methods, emphasizing the ongoing need for exploration and research in this domain.

IntroductionElite athletes' help-seeking on mental health might be influenced by their mental health literacy (MHL) and mental health experiences. The current study aimed to explore the MHL, experiences and help-seeking behaviours among elite athletes using a qualitative approach.MethodsFace-to-face semi-structured interviews were conducted among 20 Chinese elite athletes, 12 coaches, and 5 team officials. Interview data was analyzed using content analysis.ResultsSeven main themes emerged from the analysis. The current study revealed that Chinese elite athletes suffered from various mental health issues and athletes' MHL levels, help-seeking attitudes and intentions, Chinese sports environments, and Chinese cultural background could impact their help-seeking behaviours.ConclusionSupport for Chinese elite athletes' mental health and help-seeking requires improvement.

Nitrate is the main source of nitrogen for plant growth and development under aerobic conditions, which serves as an important nutrient and signaling molecule, understanding the nitrate signaling pathway is important for agricultural production. Auxin response factors (ARFs) are associated with nitrate signaling, but their underlying mechanism is less known in apples. In this study, it was found that MdARF18 can be expressed as a transcription factor activated by nitrate, and inhibited the uptake of nitrate in apples. Then, MdARF18 was found to bind directly to the TGTCTT site of the MdNRT1.1 promoter and significantly reduced its expression. In conclusion, MdARF18 regulates nitrate uptake in plants by mediating the expression of MdNRT1.1, providing insight into the mechanism by which MdARF18 regulates nitrate uptake and utilization in apples.

With the help of advanced information technology, real-time monitoring and control levels of cyber-physical distribution systems (CPDS) have been significantly improved. However due to the deep integration of cyber and physical systems, attackers could still threaten the stable operation of CPDS by launching cyber-attacks, such as denial-of-service (DoS) attacks. Thus, it is necessary to study the CPDS risk assessment and defense resource allocation methods under DoS attacks. This paper analyzes the impact of DoS attacks on the physical system based on the CPDS fault self-healing control. Then, considering attacker and defender strategies and attack damage, a CPDS risk assessment framework is established. Furthermore, risk assessment and defense resource allocation methods, based on the Stackelberg dynamic game model, are proposed under conditions in which the cyber and physical systems are launched simultaneously. Finally, a simulation based on an actual CPDS is performed, and the calculation results verify the effectiveness of the algorithm.

The development of the Energy Internet has improved the efficiency of energy utilization and promoted sustainable development of power and energy systems. The multi-energy system modeling considering the dynamic process of transmission line is one of the key research points of Energy Internet operation control. Through the energy circuit theory, the lumped parameter model of natural gas pipelines is built and the dynamic characteristic parameters under the control instruction are extracted. Combined with dynamic characteristic parameters, the long short-term memory (LSTM) neural network is designed to fit the natural gas pipeline dynamic process into discrete linear time-varying (LTV) equations. Combined with the equations, an energy hub method is used to build a control model of industrial parks with multi-energy distribution system. Using the rolling optimal control strategy given in this paper, the model is solved by the Matlab-Yalmip solver and rolling control instructions of each energy conversion unit are obtained. Finally, the case study demonstrates that the LSTM neural network-based modeling method presented in this paper can accurately fit the dynamic process of a natural gas pipeline system. The rolling control model of the multi-energy system can improve the efficiency of energy utilization, exhibit the transmission line status constraints during the optimization control process and improve reliability of the multi-energy system operation.

Objective: To explore the balance of peripheral blood T helper 17 cells/regulatory T cell (Th17/Treg) ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans (ASO). Methods: A rat model of lower extremity ASO was established, and blood samples from patients with lower extremity ASO before and after surgery were obtained. ELISA was used to detect interleukin 6 (IL-6), IL-10, and IL-17. Real-time RCR and Western blot analyses were used to detect Foxp3, IL-6, IL-10, and IL-17 expression. Moreover, flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio. Results: Compared with the control group, the iliac artery wall of ASO rats showed significant hyperplasia, and the concentrations of cholesterol and triglyceride were significantly increased (P

This paper introduces a distributed secondary control scheme for achieving current sharing and average voltage regulation objectives in a DC microgrid. The proposed scheme employs a dynamic diffusion algorithm (DDA) instead of the consensus algorithm to enable distributed communication among converters. To help understand DDA, the relation of DDA and other diffusion algorithms is discussed in detail and its superiority is shown by comparison with diffusion and consensus algorithms. Furthermore, considering the discrete nature and different sampling time of the digital controller and communication network, a z-domain model of the entire DC microgrid is established. The influence of communication and secondary control parameters on the system stability is investigated. Based on the established model, the tolerable communication rates are obtained. Real-time simulations conducted on the OPAL-RT platform validate the effectiveness of the proposed scheme, showcasing its advantages in terms of convergence speed and stability.

Abstract In this paper, we obtain a new spherically symmetric black hole surrounded by the pseudo-isothermal dark matter halo. Furthermore, to explore the effects of the pseudo-isothermal halo profile on a rotating black hole at the M87 galactic center, we derive a rotating black hole solution encompassed by the pseudo-isothermal halo by using the Newman-Janis method. Our investigation focuses on the impact of the pseudo-isothermal halo on the black hole event horizon, time-like and null orbits, as well as the black hole shadow. We find that as the spin parameter a increases, the interval between the inner event horizon and the outer event horizon of the rotating black hole surrounded by the pseudo-isothermal halo in M87 diminishes. This leads to the formation of an extreme black hole. The presence of dark matter, however, has minimal effect on the event horizon. Moreover, in the M87 as the spin parameter a increases, the black hole shadow deviates increasingly from a standard circle, with larger spin parameters causing more pronounced distortion relative to the standard circle. Surprisingly, we observe that the dark matter density has very little influence on the shadow of the black hole surrounded by the pseudo-isothermal halo in the M87. This study contributes to a deeper understanding of black hole structures and the role of dark matter in the universe.

Abstract Background The selection of prophylactic antibiotics for preventing post-operative pulmonary infections in smoking patients undergoing video-assisted thoracoscopic lung surgery (VATLS) is not clear. Methods In this retrospective cohort study, the outcomes of 572 smoking patients undergoing VATLS with prophylactic cefazolin/cefuroxime or other antibiotics were analyzed. Patients were classified as cefazolin/cefuroxime group and the control group. A 1:1 propensity score matching was also performed. Results The primary outcome of the incidence of post-operative pulmonary infection did not differ significantly between the two groups (23.7% vs 30.5%, RR = 0.777, 95%CI 0.564 ~ 1.070 p = 0.113). Similarly, secondary outcomes including the incidence of post-operative fever, the white blood cell count and neutrophils on the 3rd day after the surgery, and time for blood routine test recovery were all found without significant difference between the two groups. In the multivariate logistic regression model, no association was found between prophylactic use of cefazolin/cefuroxime and post-operative pulmonary infections after controlling other possible confounding factors (OR = 0.685, 95%CI 0.441 ~ 1.065, p = 0.093). Conclusions Prophylactic use of cefazolin/cefuroxime was not associated with more adverse clinical outcomes among smoking populations undergoing VATLS when compared with broad-spectrum antibiotics and the two drugs are still feasible for peri-operative prophylactic use for smoking population before the surgery.

Abstract Surgical resection is the only option to achieve long-term survival in cholangiocellular carcinoma (CCA). Due to limitations of health care systems and unforeseeable events, e.g., the COVID pandemic, the time from diagnosis to surgery (time-to-surgery (TTS)) has gained great interest in malignancies. Thus, we investigated whether TTS is associated with the oncological outcome in patients who underwent surgery for CCA. A cohort of 276 patients undergoing curative-intent surgery for intrahepatic and perihilar CCA excluding individuals with neoadjuvant therapy and perioperative mortality between 2010 and 2021 were eligible for analysis. Patients were grouped according to TTS (≤ 30; 31–60; 61–90; > 90 days) and compared by Kruskal–Wallis-analysis. Survival was compared using Kaplan–Meier analysis and characteristics associated with cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS) using Cox regressions. The median CSS was 39 months (3-year-CSS = 52%, 5-year-CSS = 42%) and the median RFS 20 months (3-year-CSS = 38%, 5-year-CSS = 33%). In univariable Cox regressions, TTS was not associated with CSS (p = 0.971) or RFS (p = 0.855), respectively. A grouped analysis with respect to TTS (≤ 30 days, n = 106; 31–60 days, n = 134; 61–90 days, n = 44; > 90 days, n = 29) displayed a median CSS of 38, 33, 51 and 41 months and median RFS of 17, 22, 28 and 20 months (p = 0.971 log rank; p = 0.520 log rank). No statistical difference regarding oncological risk factors were observed between the groups. This study is the first comprehensive analysis of TTS in CCA patients. Within a representative European cohort, TTS was not associated with earlier tumor recurrence or reduced CCS.

Abstract Robust hydrogels offer a candidate for artificial skin of bionic robots, yet few hydrogels have a comprehensive performance comparable to real human skin. Here, we present a general method to convert traditional elastomers into tough hydrogels via a unique radiation-induced penetrating polymerization method. The hydrogel is composed of the original hydrophobic crosslinking network from elastomers and grafted hydrophilic chains, which act as elastic collagen fibers and water-rich substances. Therefore, it successfully combines the advantages of both elastomers and hydrogels and provides similar Young’s modulus and friction coefficients to human skin, as well as better compression and puncture load capacities than double network and polyampholyte hydrogels. Additionally, responsive abilities can be introduced during the preparation process, granting the hybrid hydrogels shape adaptability. With these unique properties, the hybrid hydrogel can be a candidate for artificial skin, fluid flow controller, wound dressing layer and many other bionic application scenarios.

For atmospheric melting cast Cu–15Ni–8Sn alloy, hot extrusion tests were conducted on ingots of Cu–15Ni–8Sn alloy with varying extrusion ratios (5, 12 and 16) following homogenization and annealing. The investigation employed mechanical property tests, scanning electron microscopy and transmission electron microscopy to analyze the mechanical characteristics, dynamic recrystallization and twinning behaviors of the alloys subjected to different extrusion ratios. The findings revealed a reduction in the average grain size of the alloy as the extrusion ratio increased. The alloy undergoes dynamic recrystallization during hot extrusion, and the degree of recrystallization of the alloy escalated with higher extrusion ratios. The alloy underwent completely recrystallized at an extrusion ratio of 16, primarily driven by discontinuous dynamic recrystallization (DDRX). In addition, the alloy generated twins during the DRX process, and the twin boundaries provided favorable sites for the nucleation of DRX grains, which promoted the DRX of the alloy. Notably, at an extrusion ratio of 16, the alloy demonstrated impressive mechanical properties, with an ultimate tensile strength of 836 MPa and an elongation of 13.5 %. These results presented a substantial enhancement, showcasing a 54 % increase in the extruded ultimate tensile strength and a 350 % increase in the elongation compared to that of the alloy in the homogenized annealed state.

Abstract Accurately capturing domain-domain interactions is key to understanding protein function and designing structure-based drugs. Although AlphaFold2 has made a breakthrough on single domain, it should be noted that the structure modeling for multi-domain protein and complex remains a challenge. In this study, we developed a multi-domain and complex structure assembly protocol, named DeepAssembly, based on domain segmentation and single domain modeling algorithms. Firstly, DeepAssembly uses a population-based evolutionary algorithm to assemble multi-domain proteins by inter-domain interactions inferred from a developed deep learning network. Secondly, protein complexes are assembled by means of domains rather than chains using DeepAssembly. Experimental results show that on 219 multi-domain proteins, the average inter-domain distance precision by DeepAssembly is 22.7% higher than that of AlphaFold2. Moreover, DeepAssembly improves accuracy by 13.1% for 164 multi-domain structures with low confidence deposited in AlphaFold database. We apply DeepAssembly for the prediction of 247 heterodimers. We find that DeepAssembly successfully predicts the interface (DockQ ≥ 0.23) for 32.4% of the dimers, suggesting a lighter way to assemble complex structures by treating domains as assembly units and using inter-domain interactions learned from monomer structures.

Abstract Twisted tape is one of the active thermal proficiency boosting technology which has been deeply examined because to consistent efficiency findings and easy implementations. Thermo-hydraulic effectiveness of tubes fitted with twisted tapes is becoming highly significant. Although twisted tapes can cause swirls and disturb boundary layers, this is the most widely used method for improving convection. In the present attempt, to enhance the heat transfer twisted tape is inserted in tube. In the current modern research, the effect of twisted tape, on the enhancement of thermal transport, Nusselt number and friction factor performance of AIN–Al2O3/water hybrid nanofluid is evaluating utilizing CFD and ANSYS-FLUENT software. the consequence of twisted pitch 44 mm, 66 mm, 88 mm, 100 mm and Reynolds numbers 800, 1200, 1600 and 2000 on Nusselt number, heat transfer coefficient and friction coefficient have been computed numerically with 0.01 to 0.04 volume friction of nanopowders. The commercial ANSYS-FLUENT code was used in this analysis utilizing the SIMPLE method for pressure–velocity coupling. The $$K - \omega$$ K - ω model and Navier Stokes equations are integrating utilizing finite volume method in ANSYS-FLUENT. It was observed that inserting the twisted tape in tube significantly improves the thermal conductivity as well as friction factor compared with the simple tube without turbulator.

Abstract Background Previous observational studies have documented an inverse association of birthweight with myocardial infarction (MI) but a positive association with atrial fibrillation (AF). However, the causality of these associations and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of birthweight, incorporating both fetal and maternal genetic effects, on MI and AF, and identify potential mediators in their respective pathways. Methods We performed Mendelian randomization (MR) analyses using genome-wide association study summary statistics for birthweight (N = 297,356 for own birthweight and 210,248 for offspring birthweight), MI (Ncase=61,000, Ncontrol=577,000), AF (Ncase=60,620, Ncontrol=970,216), and 52 candidate mediators (N = 13,848-1,295,946). Two-step MR was employed to identify and assess the mediation proportion of potential mediators in the associations of birthweight with MI and AF, respectively. As a complement, we replicated analyses for fetal-specific birthweight and maternal-specific birthweight. Results Genetically determined each 1-SD lower birthweight was associated with a 40% (95% CI: 1.22–1.60) higher risk of MI, whereas each 1-SD higher birthweight was causally associated with a 29% (95% CI: 1.16–1.44) higher risk of AF. Cardiometabolic factors, including lipids and lipoproteins, glucose and insulin, blood pressure, and fatty acids, each mediated 4.09-23.71% of the total effect of birthweight on MI, followed by body composition and strength traits (i.e., appendicular lean mass, height, and grip strength) and socioeconomic indicators (i.e., education and household income), with the mediation proportion for each factor ranging from 8.08 to 16.80%. By contrast, appendicular lean mass, height, waist circumference, childhood obesity, and body mass index each mediated 15.03-45.12% of the total effect of birthweight on AF. Both fetal-specific birthweight and maternal-specific birthweight were inversely associated with MI, while only fetal-specific birthweight was positively associated with AF. Psychological well-being and lifestyle factors conferred no mediating effect in either association. Conclusions Cardiometabolic factors mainly mediated the association between lower birthweight and MI, while body composition and strength traits mediated the association between higher birthweight and AF. These findings provide novel evidence for the distinct pathogenesis of MI and AF and advocate adopting a life-course approach to improving fetal development and subsequent causal mediators to mitigate the prevalence and burden of cardiovascular diseases.

Abstract Pancreatic cancer is highly lethal, of which 90% is pancreatic ductal adenocarcinoma (PDAC), with a 5-year survival rate of less than 12%, lacking effective treatment options and late diagnosis. Furthermore, the tumors show an intense resistance to cytotoxic chemotherapies. As autophagy is elevated in PDAC, targeting the autophagic pathway is regarded as a promising strategy for cancer treatment. Immunofluorescence and transmission electron microscopy were utilized to assess the autophagic flux. Label-free quantitative phosphoproteomics was used to figure out critically altered tyrosine phosphorylation of the proteins. Tumor-bearing mice were used to validate that SH2 TrM-(Arg)9 restrained the growth of tumor cells. SH2 TrM-(Arg)9 inhibited collagen-induced autophagy via blocking the DDR1/PYK2/ERK signaling cascades. SH2 TrM-(Arg)9 improved the sensitivity of PANC-1/GEM cells to gemcitabine (GEM). Inhibition of autophagy by SH2 TrM-(Arg)9 may synergized with chemotherapy and robusted tumor suppression in pancreatic cancer xenografts. SH2 TrM-(Arg)9 could enter into PDAC cells and blockade autophagy through inhibiting DDR1/PYK2/ERK signaling and may be a new treatment strategy for targeted therapy of PDAC.

This study aims to investigate the influence of rigid polyurethane foam (RPUF) as a filling material on the energy absorption performance of thin-walled tubes through experiments. Hybrid graphene oxide-silica nanoparticles (GO-SiO2) was prepared using the electrostatic adsorption method and its potential application in RPUF enhancement were investigated. The interaction between GO and nano SiO2 inhibits the agglomeration of each other and improved the mechanical properties and energy absorption capacity of RPUF. When the GO-SiO2 hybrid content was 6 wt%, the compressive strength and total energy absorption of the GO-SiO2/RPUF composite material increased by 99.59% and 89.63% compared with those of pure RPUF, respectively. In addition, the deformation characteristics of empty tube and foam-filled tube under lateral compression were compared, and the influence of the RPUF material’s mechanical properties on the energy absorption characteristics of foam-filled tube was further analyzed. Test results show that the foam material can effectively improve the stability of the compression deformation of thin-walled circular tubes and improve the compression resistance of the structure. Improving the mechanical properties of RPUF materials can further increase the bearing capacity and energy absorption of foam-filled tubes. The results in this study validated the feasibility of using GO-SiO2 hybrid as a new nano-reinforcing filler for RPUF, and provide an experimental reference for the engineering application of foam-filled tubes as energy absorption components.

Abstract China has became the world’s second largest pharmaceutical market, and the number of her registered clinical trials exceeded 3000 in 2021. Although thousands of healthy volunteers are participating in a large number of clinical trials in this country, there is no report about the characteristics, recognition, attitude of Chinese healthy volunteers and their concerns of clinical trials. A questionnaire survey was designed and given to 324 healthy volunteers participating in clinical trials in Wuhan, China. Four important findings emerged from our data. First, young, single and less educated men constituted the majority of Chinese healthy volunteers. Second, differences between the male and female healthy volunteers were observed. Female healthy volunteers are supposed to face more challenges and pressure in life, be more cautious about the clinical trials and more concerned about their health and feelings than the male. Third, no sociodemographic characteristic was associated with poorly understanding of the protocol research content, which was subjectively evaluated. Fourth, more support from society/family and more positive media reports about the participation of healthy volunteers in clinical trials are badly needed. These findings would help us to get a better understanding of Chinese healthy volunteers as a group for protecting them and promoting drug development.

Abstract Background Emerging metabolomics-based studies suggested links between amino acid metabolism and metabolic dysfunction-associated fatty liver disease (MAFLD) risk; however, whether there exists an aetiological role of amino acid metabolism in MAFLD development remains unknown. The aim of the present study was to assess the causal relationship between circulating levels of amino acids and MAFLD risk. Methods We conducted a two-sample Mendelian randomization (MR) analysis using summary-level data from genome-wide association studies (GWAS) to evaluate the causal relationship between genetically predicted circulating levels of amino acids and the risk of MAFLD. In the discovery MR analysis, we used data from the largest MAFLD GWAS (8434 cases and 770,180 controls), while in the replication MR analysis, we used data from a GWAS on MAFLD (1483 cases and 17,781 controls) where MAFLD cases were diagnosed using liver biopsy. We used Wald ratios or inverse variance-weighted (IVW) methods in the MR main analysis and weighted median and MR-Egger regression analyses in sensitivity analyses. Furthermore, we performed a conservative MR analysis by restricting genetic instruments to those directly involved in amino acid metabolism pathways. Results We found that genetically predicted higher alanine (OR = 1.43, 95% CI 1.13–1.81) and lower glutamine (OR = 0.83, 95% CI 0.73–0.96) levels were associated with a higher risk of developing MAFLD based on the results from the MR main and conservative analysis. The results from MR sensitivity analyses and complementary analysis using liver proton density fat fraction as a continuous outcome proxying for MAFLD supported the main findings. Conclusions Novel causal metabolites related to MAFLD development were uncovered through MR analysis, suggesting future potential for evaluating these metabolites as targets for MAFLD prevention or treatment.

The authors report a case of a 29-year-old male presented with bilateral breast enlargement with no significant past medical history or estrogen exposure. Serum β-human chorionic gonadotropin (HCG) was 14,306.60 mIU and positron emission tomography-computed tomography discovered a malignant mass on the right side of anterior superior mediastinum. Magnetic resonance imaging demonstrated pituitary microadenoma. Pathological biopsy showed poorly differential pituitary adenoma and immunohistochemical staining displayed that CK(+), PLAP(−), AFP(−), HCG(+), CD30(−), Oct3/4(−), CK7(+), TTF-1(−), CD117(−), Ki 67(80+), CK5/6(−), EMA(partial+), inhibin(partial+). A diagnosis of primary anterior mediastinal choriocarcinoma metastasis to bilateral lungs accompanied with pituitary microadenoma was confirmed. Then the patient received chemotherapy combined with immunotherapy. But serum β-HCG level was still above the normal, and unfortunately, the patient died 6 months after his diagnosis. This case inspires us to think of the possibility of choriocarcinoma when a man presents gynecomastia or lung metastatic symptoms, adding Opdivo to the chemotherapy might not improve the poor treatment outcomes.

Purpose: Different arch structures may cause different foot function injuries. In the past, the arch structure and flexibility of the foot were often defined by the height of the arch, and there was no three-dimensional (3D) structure classification method. In order to form a more complete 3D description, we propose a new classification system of arch volume flexibility (AVF), and then use this new classification system to investigate the relationship between the AVF and arch index (AI), and the arch height flexibility (AHF) and AI, respectively. Methods: It is proposed to recruit 180 young male adults for the test. We obtained arch volume and AI through 3D scanning and obtained the navicular height through manual measurement. Based on these data, we calculated the AHF and the AVF. Using the quintile method, these arches are divided into very stiff, stiff, neutral, flexible, and very flexible. According to AI value, all arches were divided into cavus, rectus, and planus. The distribution of AVF was compared using χ2 goodness of fit test. The spearman correlation test was used to compare the AHF and AVF. A p

Abstract The marked increase in the incidence rate of brucellosis is a serious public health concern in Jiangsu Province. However, its temporal and spatial distribution has not been studied in depth. The main purpose of this study is to depict the demographic, temporal and spatial distribution patterns and clustering characteristics of brucellosis cases in Jiangsu Province, China, from 2006 to 2021 to develop and implement effective scientific prevention and control strategies. Data for human brucellosis cases in Jiangsu Province from 2006 to 2021 were obtained from the Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS). Spatial autocorrelation analysis and temporal-spatial scan statistics were used to identify potential changes in the spatial and temporal distributions of human brucellosis in Jiangsu Province. During the years 2006–2021, 1347 brucellosis cases were reported in Jiangsu Province, with an average annual incidence rate of 0.1036 per 100,000 individuals. Middle-aged and elderly individuals (aged 40–69 years) were the main infected populations, accounting for 69.72% (939/1347) of all reported cases. The incidence of brucellosis in Jiangsu showed a long-term increasing trend and displayed pronounced seasonal variations, with the peak occurring between April and June annually. The incidence gradually expanded from the northern and southern areas to the central areas between 2006 and 2021. Global spatial autocorrelation analysis demonstrated a positive correlation in the incidence of brucellosis between 2008 and 2012–2021. Temporal-spatial clustering analysis showed that the primary cluster was detected in the northern, highly endemic regions of Jiangsu, and the three secondary clusters were in areas where there had been outbreaks of brucellosis. Human brucellosis remains a serious public health issue in Jiangsu Province. Northern and southern Jiangsu regions, with high rates of brucellosis, may require special plans and measures to monitor and control the disease. Additionally, the capacity to respond to outbreaks in high-incidence areas should be improved to prevent further brucellosis outbreaks.

Investigating the surface morphology and microstructure of laser powder bed fusion (L-PBF) in solidification and optimizing process parameters is crucial for improving the accuracy and performance of cladding parts of GH3536 superalloy. In this study, a computational model incorporating Computational Fluid Dynamics (CFD) and Discrete Element Method (DEM) was utilized to simulate the mesoscale evolution of the molten pool in L-PBF for GH3536 superalloy. Furthermore, the growth of columnar dendrites along the fusion boundary under transient conditions was simulated utilizing a quantitative phase-field model. The impact of scanning speed and laser power on temperature distribution, molten pool size, surface morphology of cladding layer, and columnar dendrite spacing during solidification of single-track L-PBF were examined. The findings suggest that the molten pool undergoes a fast process characterized by significant temperature gradients. Increasing the laser power or reducing the scanning speed results in higher maximum molten pool temperature, as well as increased molten pool depth and width. Overlarge or undersized scanning speed and laser power can result in poor surface quality of the cladding layer. When the laser power was 120 W and the scan speed was 0.4 m/s, the cladding layer exhibited improved surface morphology, with finer columnar dendrites observed at the molten pool's base. This study delved into understanding the evolution characteristics of the molten pool and the growth process of columnar dendrites at the molten pool's base, providing valuable insights for determining appropriate experimental process parameters for L-PBF of GH3536 superalloy.

In coal seam groups where the spacing between the upper and lower seams is small, the lower seam working face is significantly influenced by residual coal pillars from the upper seam and the void spaces created during mining. This presents considerable challenges for underground mining safety. Through field investigations, the layout of the coal seam quarry above the working face of the 3−1 coal seam in Yanghuopan Mine was examined, along with the distribution of the residual coal pillars. This allowed for the identification of the interlayer rock strata characteristics. Subsequently, we analyzed the mechanism of directional hydraulic fracturing and decompression to determine the key parameters of the 3−1 coal seam. Using the Rock Fracture Process Analysis 3D (RFPA 3D) numerical simulation, we evaluated the effects of various factors on the initiation and propagation of hydraulic fracturing-induced cracks, formulated the evolution law of these fractures, and incorporated the damage variables into the analysis. Additionally, we assessed the influence of different parameters on crack initiation and extension during hydraulic fracturing, using RFPA 3D simulations to derive the evolution law governing directional hydraulic fractures. This allowed us to define the hydraulic fracturing parameters for the 3−1 interbedded rock layers by integrating the process parameter calculations with the damage variables. Based on these findings, an on-site implementation plan was developed and executed, followed by a comprehensive evaluation of the construction results. The study concludes that directional hydraulic fracturing and decompression effectively contribute to the prevention and control of roof-related disasters in the mining of lower coal seams where seam spacing is minimal. This research offers valuable theoretical insights and practical reference for disaster prevention and control in similar geological conditions.

The diel vertical variations of chlorophyll a (Chl-a) concentration are thought of primarily as an external manifestation of regulating phytoplankton’s biomass, which is essential for dynamically estimating the biogeochemical cycle in inland waters. However, information on these variations is limited due to insufficient measurements. Undersampled observations lead to delayed responses in phytoplankton assessment, impacting accurate evaluations of carbon export and water quality in dynamic inland waters. Here, we report the first lidar-observed diel vertical variations of inland Chl-a concentration. Strong agreement with r2 of 0.83 and a root mean square relative difference (RMSRD) of 9.0% between the lidar-retrieved and in situ measured Chl-a concentration verified the feasibility of the Mie–fluorescence–Raman lidar (MFRL). An experiment conducted at a fixed observatory demonstrated the lidar-observed diel Chl-a concentration variations. The results showed that diel variations of Chl-a and the formation of subsurface phytoplankton layers were driven by light availability and variations in water temperature. Furthermore, the facilitation from solar radiation-regulated water temperature on the phytoplankton growth rate was revealed by the high correlation between water temperature and Chl-a concentration anomalies. Lidar technology is expected to provide new insights into continuous three-dimension observations and be of great importance in dynamic inland water ecosystems.

The forming quality of profiled ring rolling not only encompasses macroscopic accuracy but also emphasizes the microstructure. Due to the multiple process parameters and complex metal flow during profiled ring rolling, the various forming defects are difficult to control and difficult to study theoretically. The objective of this study is to establish a comprehensive method for evaluating the forming quality of profiled rings, which considers both the macroscopic forming accuracy and the microstructure. Firstly, the synthetic size factor was defined, and the evolutionary relation between the section forming rate and the diameter growth rate of E-section ring rolling was analyzed in detail. The synthetic size factor can be used to describe the dimensional evolution and evaluate the forming accuracy of the profiled ring rolling process. Taking into full consideration the features of intermittent deformation in local areas, a microstructure evolution model of the Inconel718 alloy during E-section ring rolling, which can accurately predict the recrystallization volume fraction and average grain size of the final ring, was established. Then, combined with finite element simulation, the influence of the rotation speed of the driving roll on the macro-size evolution and microstructure was systematically analyzed. The results indicate that there is often a discrepancy between dimensional accuracy and microstructure uniformity in the optimization trend. For instance, the higher the rotation speed of the driving roll is, the more uniform the microstructure is, but the more difficult it is for the section profile to form. Finally, combined with response surface methodology (RSM), multi-parameter optimization was carried out with section forming accuracy and grain uniformity as the optimization objectives. By using the optimal parameters, an E-section ring with a complete profile and a uniform microstructure was obtained, with a maximum prediction error of the recrystallization volume fraction lower than 5%. The results show that the macroscopic and microscopic quality evaluation methods proposed in this study, as well as the optimization method combining RSM, can be effectively applied to the process optimization of profiled ring rolling.

Background: Mitophagy is a crucial process involved in maintaining cellular homeostasis by selectively eliminating damaged or surplus mitochondria. As the kidney is an organ with a high dynamic metabolic rate and abundant mitochondria, it is particularly crucial to control mitochondrial quality through mitophagy. Dysregulation of mitophagy has been associated with various renal diseases, including acute and chronic kidney diseases, and therefore a better understanding of the links between mitophagy and these diseases may present new opportunities for therapeutic interventions. Summary: Mitophagy plays a pivotal role in the development of kidney diseases. Upregulation and downregulation of mitophagy have been observed in various kidney diseases, such as renal ischemia-reperfusion injury, contrast-induced acute kidney injury, diabetic nephropathy, kidney fibrosis, and several inherited renal diseases. A growing body of research has suggested that PINK1 and Parkin， the main mitophagy regulatory proteins， represent promising potential therapeutic targets for kidney diseases. In this review, we summarize the latest insights into how the progression of renal diseases can be mitigated through the regulation of mitophagy, while highlighting their performance in clinical trials. Key Message: This review comprehensively outlines the mechanisms of mitophagy and its role in numerous kidney diseases. While early research holds promise, most mitophagy-centered therapeutic approaches have yet to reach the clinical application stage.

In order to improve the dynamic performance during the startup process of hydropower units, while considering the efficient and stable speed increase and effective suppression of water pressure fluctuations and mechanical vibrations, optimization algorithms must be used to select the optimal parameters for the system. However, in current research, various multi-objective optimization algorithms still have limitations in terms of target space coverage and diversity maintenance in parameter optimization during the startup process of hydraulic turbines. To explore and verify the optimal algorithms and parameters for the startup process of hydraulic turbines, multiple multi-objective optimization strategies are proposed in this study. Under the condition of constructing a fine-tuned nonlinear model of the control system, this paper focuses on three key indicators: the absolute integral of the speed deviation, the absolute integral of the snail shell water pressure fluctuation, and the relative value of the maximum axial water thrust. Through comparative analysis of the multi-objective particle swarm optimization algorithm (MOPSO), variant multi-objective particle swarm optimization algorithm (VMOPSO), multi-objective sine cosine algorithm (MOSCA), multi-objective biogeography algorithm (MOBBO), multi-objective gravity search algorithm (MOGAS), and improved multi-objective particle swarm optimization algorithm (IMOPSO), the obtained optimal parameters are compared and analyzed to select the optimal multi-objective optimization strategy, and the most suitable parameters for actual working conditions are selected through a comprehensive weighting method. The results show that, compared to the local optimal solution problem caused by other optimization algorithms, the improved multi-objective optimization method significantly reduces water pressure fluctuations and mechanical vibrations while ensuring stable speed improvement, achieving better control performance. The optimization results have significant guiding significance for ensuring the smooth operation and safety of hydropower units, and provide strong support for making operational decisions.

Although the metallization of semiconductor bulk LiBC has been experimentally achieved, various flaws, including the strong lattice distortion, the uncontrollability of phase transition under pressure, usually appear. In this work, based on the first-principles calculations, we propose a new way of hydrogenation to realize metallization. Using the fully anisotropic Migdal-Eliashberg theory, we investigate the superconducting behaviors in the stable monolayers LiBCH and LiCBH, in which C and B atoms are hydrogenated, respectively. Our findings indicate that the monolayers possess the high T_{c} of 82.0 and 82.5 K, respectively, along with the interesting three-gap superconducting natures. The Fermi sheets showing the obvious three-region distribution characteristics and the abnormally strong electron-phonon coupling are responsible for the high-T_{c} three-gap superconductivity. Furthermore, the T_{c} can be dramatically boosted up to 120.0 K under 3.5% tensile strain. To a great extent, the high T_{c} is beyond the liquid nitrogen temperature (77 K), which is beneficial for the applications in future experiments. This study not only explores the superconducting properties of the monolayers LiBCH and LiCBH, but also offers practical insights into the search for high-T_{c} superconductors.