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AIM: To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. METHODS: For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. RESULTS: The OCTA data demonstrated a statistically significant difference (P

Slope stability analysis is a classical mechanical problem in geotechnical engineering and engineering geology. It is of great significance to study the stability evolution of expansive soil slopes for engineering construction in expansive soil areas. Most of the existing studies evaluate the slope stability by analyzing the limit equilibrium state of the slope, and the analysis method for the stability evolution considering the damage softening of the shear zone is lacking. In this study, the large deformation shear mechanical behavior of expansive soil was investigated by ring shear test. The damage softening characteristic of expansive soil in the shear zone was analyzed, and a shear damage model reflecting the damage softening behavior of expansive soil was derived based on the damage theory. Finally, by skillfully combining the vector sum method and the shear damage model, an analysis method for the stability evolution of the expansive soil slope considering the shear zone damage softening was proposed. The results show that the shear zone subjected to large displacement shear deformation exhibits an obvious damage softening phenomenon. The damage variable equation based on the logistic function can be well used to describe the shear damage characteristics of expansive soil, and the proposed shear damage model is in good agreement with the ring shear test results. The vector sum method considering the damage softening behavior of the shear zone can be well applied to analyze the stability evolution characteristics of the expansive soil slope. The stability factor of the expansive soil slope decreases with the increase of shear displacement, showing an obvious progressive failure behavior.

The effectiveness of AI-driven drug discovery can be enhanced by pretraining on small molecules. However, the conventional masked language model pretraining techniques are not suitable for molecule pretraining due to the limited vocabulary size and the non-sequential structure of molecules. To overcome these challenges, we propose FragAdd, a strategy that involves adding a chemically implausible molecular fragment to the input molecule. This approach allows for the incorporation of rich local information and the generation of a high-quality graph representation, which is advantageous for tasks like virtual screening. Consequently, we have developed a virtual screening protocol that focuses on identifying estrogen receptor alpha binders on a nucleus receptor. Our results demonstrate a significant improvement in the binding capacity of the retrieved molecules. Additionally, we demonstrate that the FragAdd strategy can be combined with other self-supervised methods to further expedite the drug discovery process.

Abstract Osteoarthritis is a degenerative joint disease with joint pain as the main symptom, caused by fibrosis and loss of articular cartilage. Due to the complexity and heterogeneity of osteoarthritis, there is a lack of effective individualized disease-modifying osteoarthritis drugs in clinical practice. Chondrocyte senescence is reported to participate in occurrence and progression of osteoarthritis. Here we show that small molecule 10-hydroxy-2-decenoic acid suppresses cartilage degeneration and relieves pain in the chondrocytes, cartilage explants from osteoarthritis patients, surgery-induced medial meniscus destabilization or naturally aged male mice. We further confirm that 10-hydroxy-2-decenoic acid exerts a protective effect by targeting the glycosylation site in the Asp_Arg_Hydrox domain of aspartyl β-hydroxylase. Mechanistically, 10-hydroxy-2-decenoic acid alleviate cellular senescence through the ERK/p53/p21 and GSK3β/p16 pathways in the chondrocytes. Our study uncovers that 10-hydroxy-2-decenoic acid modulate cartilage metabolism by targeting aspartyl β-hydroxylase to inhibit chondrocyte senescence in osteoarthritis. 10-hydroxy-2-decenoic acid may be a promising therapeutic drug against osteoarthritis.

Abstract Background The prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC. Methods The association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/β-catenin pathway. Results BRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/β-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/β-catenin pathway by decreasing the K63-linked ubiquitination of β-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression. Conclusions Our research results emphasize the critical role of the BRCC36-β-catenin axis in VC, suggesting that BRCC36 or β-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients. Graphical Abstract

AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P

Abstract The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e–h+) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (1O2) via e–h+ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors. Graphical abstract

Abstract Objective This study aimed to examine the relationship between different dimensions of depressive symptoms and the presence of diabetes mellitus in hemodialysis patients. Additionally, the study sought to elucidate the mediating effect of physical performance on this association. Methods This was a cross-sectional multicenter study conducted between July 2020 and March 2023, involving 1024 patients from eight hemodialysis centers in Shanghai. Diabetes mellitus was based on a documented physician diagnosis and blood glucose tests. Physical performance and depressive symptoms were assessed using short-physical performance battery (SPPB) and the patient health questionnaire-9, respectively. Regression and mediation analysis were applied to statistical analysis. Results Among the 1024 participants, 39.26% (n = 402) were found to have coexisting diabetes mellitus. Diminished SPPB scores (OR = 0.843, 95% CI = 0.792–0.897) and cognitive depressive symptoms (OR = 1.068, 95% CI = 1.011–1.129) exhibited significant associations with diabetes mellitus, while somatic depressive symptoms did not show a significant correlation. Notably, SPPB emerged as a complete mediator in the relationship between cognitive depressive symptoms and diabetes mellitus. The observed indirect effect of SPPB on this relationship was estimated at 0.038 (95% CI: 0.021–0.057). Conclusion This study showed an association between diabetes mellitus and cognitive depressive symptoms in patients undergoing hemodialysis, with physical performance appearing to mediate the relationship between diabetes mellitus and depressive symptoms.

Abstract Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1–C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Abstract Background The prevalence of obesity is escalating. Previous research has concentrated on the link between frailty and obesity; however, the association between prefrailty and obesity has been less studied. Prefrailty screening and intervention may prevent or postpone frailty in older persons. Objective The study was to investigate into the relationship between prefrailty and several obesity indicators in Chinese community-dwelling older individuals. Methods This research employed the Frailty Screening Index to investigate the frailty phenotype of people living in Shanghai. Bioelectrical impedance analysis was used for evaluating body composition. Results There were 510 participants (39.0%) with high visceral adipose areas. Participants with a high visceral adipose area showed a higher risk of prefrailty (adjusted OR, 1.53; 95% CI, 1.19–1.96), according to multivariate models. When body mass index (BMI) and visceral fat area (VFA) were combined, it was discovered that having an overweight BMI with normal VFA was a protective factor for prefrailty (corrected OR, 0.62; 95% CI, 0.43–0.90), but having a normal weight but excess VFA increased the risk of prefrailty (corrected OR, 1.87; 95% CI, 1.15–3.03). Conclusion Visceral fat obesity is an independent risk factor for prefrailty in Chinese older adults. Implementing targeted interventions, such as dietary modifications, increased physical activity, and other lifestyle changes, could play a crucial role in reducing the risk of prefrailty and improving overall health outcomes in this population.

Abstract Background Diabetes mellitus (DM) affects up to one-third of breast cancer (BC) patients. Patients with co-existing BC and DM (BC-DM) have worsened BC prognosis. Nevertheless, the molecular mechanisms orchestrating BC-DM prognosis remain poorly understood. tRNA-derived fragments (tRFs) have been shown to regulate cancer progression. However, the biological role of tRFs in BC-DM has not been explored. Methods tRF levels in tumor tissues and cells were detected by tRF sequencing and qRT-PCR. The effects of tRF on BC cell malignancy were assessed under euglycemic and hyperglycemic conditions in vitro. Metabolic changes were assessed by lactate, pyruvate, and extracellular acidification rate (ECAR) assays. Diabetic animal model was used to evaluate the impacts of tRF on BC tumor growth. RNA-sequencing (RNA-seq), qRT-PCR, Western blot, polysome profiling, luciferase reporter assay, and rescue experiments were performed to explore the regulatory mechanisms of tRF in BC-DM. Results We identified that tRF-Cys-GCA-029 was downregulated in BC-DM tissues and under hyperglycemia conditions in BC cells. Functionally, downregulation of tRF-Cys-GCA-029 promoted BC cell proliferation and migration in a glucose level-dependent manner. tRF-Cys-GCA-029 knockdown also enhanced glycolysis metabolism in BC cells, indicated by increasing lactate/pyruvate production and ECAR levels. Notably, injection of tRF-Cys-GCA-029 mimic significantly suppressed BC tumor growth in diabetic-mice. Mechanistically, tRF-Cys-GCA-029 regulated BC cell malignancy and glycolysis via interacting with PRKCG in two ways: binding to the coding sequence (CDS) of PRKCG mRNA to regulate its transcription and altering polysomal PRKCG mRNA expression to modify its translation. Conclusions Hyperglycemia-downregulated tRF-Cys-GCA-029 enhances the malignancy and glycolysis of BC cells. tRF-Cys-GCA-029-PRKCG-glycolysis axis may be a potential therapeutic target against BC-DM. Graphical Abstract

Abstract Alkaline hydrogen evolution reaction (HER) for scalable hydrogen production largely hinges on addressing the sluggish bubble‐involved kinetics on the traditional Ni‐based electrode, especially for ampere‐level current densities and beyond. Herein, 3D‐printed Ni‐based sulfide (3DPNS) electrodes with varying scaffolds are designed and fabricated. In situ observations at microscopic levels demonstrate that the bubble escape velocity increases with the number of hole sides (HS) in the scaffolds. Subsequently, we conduct multiphysics field simulations to illustrate that as the hole shapes transition from square, pentagon, and hexagon to circle, where a noticeable reduction in the bubble‐attached HS length and the pressure balance time around the bubbles results in a decrease in bubble size and an acceleration in the rate of bubble escape. Ultimately, the 3DPNS electrode with circular hole configurations exhibits the most favorable HER performance with an overpotential of 297 mV at the current density of up to 1000 mA cm−2 for 120 h. The present study highlights a scalable and effective electrode scaffold design that promotes low‐cost and low‐energy green hydrogen production through the ampere‐level alkaline HER.

Abstract Celiac Disease (CD) is a primary malabsorption syndrome resulting from the interplay of genetic, immune, and dietary factors. CD negatively impacts daily activities and may lead to conditions such as osteoporosis, malignancies in the small intestine, ulcerative jejunitis, and enteritis, ultimately causing severe malnutrition. Therefore, an effective and rapid differentiation between healthy individuals and those with celiac disease is crucial for early diagnosis and treatment. This study utilizes Raman spectroscopy combined with deep learning models to achieve a non-invasive, rapid, and accurate diagnostic method for celiac disease and healthy controls. A total of 59 plasma samples, comprising 29 celiac disease cases and 30 healthy controls, were collected for experimental purposes. Convolutional Neural Network (CNN), Multi-Scale Convolutional Neural Network (MCNN), Residual Network (ResNet), and Deep Residual Shrinkage Network (DRSN) classification models were employed. The accuracy rates for these models were found to be 86.67%, 90.76%, 86.67% and 95.00%, respectively. Comparative validation results revealed that the DRSN model exhibited the best performance, with an AUC value and accuracy of 97.60% and 95%, respectively. This confirms the superiority of Raman spectroscopy combined with deep learning in the diagnosis of celiac disease.

In order to solve the shortcomings of the existing mining robot path planning methods, such as low efficiency, slow convergence speed, and easy to fall into local optimum, a path planning method based on Actor-Critic algorithm is proposed. Firstly, according to the real-time position information of the inspection target and the obstacles, the steering angle of the patrol robot is calculated and the forward direction is determined, which can significantly improve the efficiency of path planning. With the goal of minimizing energy consumption and avoiding collisions, the patrol robot learns the target inspection sequence and forward speed according to the dynamically changing mining environment. Because the dynamic and continuous changes of the mine environment lead to a high state dimension, the action and reward generated by the continuous state are estimated by the deep learning networks. In order to improve the efficiency of learning, two networks are adopted, namely the Actor network and the Critic network, to achieve real-time update of strategy and value. The simulation results show that the proposed method can design a safe and reasonable patrol route in a dynamic environment, and can complete the patrol task with a 98% success probability and lower energy consumption.

Abstract The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

Abstract Background In critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial. Methods Clinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group ( 7 days), and the prognosis of the two groups was analyzed. Results A total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876–0.919), and 0.896 (95% CI: 0.866–0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p

Abstract This article analyzes and compares the news values constructed in the English news reporting from Chinese and US mainstream media around events concerning maritime security, revealing how the related events have been packaged and sold differently in the two societies, uncovering the discrepancies in Chinese and US social visions on maritime security, and exploring the social attitudes underpinning the constant conflicts between the two countries in the marine sphere. Adopting corpus linguistic methods and the discursive news values analysis (DNVA) framework, this study examines news values through keywords, naming strategies, and images contained in Chinese and US mainstream English news outlets. The results show that Chinese media established the news values of Positivity and Proximity prominently through both textual and visual reporting, by emphasizing common international interests, advocating diplomatic joint cooperation and demonstrating optimistic attitudes towards the future of marine environment. By contrast, US media keenly construed Negativity and Eliteness, by highlighting the exclusive national interests/security of the US, dwelling on threats from other countries and distinctly demonstrating worries, fears, anger and violence. The differences in newsworthiness reflect that maritime security has been constructed in discrepant ways in Chinese and US society: as international joint security with optimistic perspective in China, and as exclusive national security with pessimistic perspective in US. This study has improved and supplemented the results of the previous China-US marine policy studies by the findings of the social emotions/cognition towards maritime policy revealed through newsworthiness analysis.

Abstract As one of the most attractive methods for the synthesis of ordered hierarchically porous crystalline materials, the soft-template method has not appeared in covalent organic frameworks (COFs) due to the incompatibility of surfactant self-assembly and guided crystallization process of COF precursors in the organic phase. Herein, we connect the soft templates to the COF backbone through ionic bonds, avoiding their crystallization incompatibilities, thus introducing an additional ordered arrangement of soft templates into the anionic microporous COFs. The ion exchange method is used to remove the templates while maintaining the high crystallinity of COFs, resulting in the construction of COFs with ordered hierarchically micropores/mesopores, herein named OHMMCOFs (OHMMCOF-1 and OHMMCOF-2). OHMMCOFs exhibit significantly enhanced functional group accessibility and faster mass transfer rate. The extrinsic porosity can be adjusted by changing the template length, concentration, and ratio. Cationic guanidine-based COFs (OHMMCOF-3) are also constructed using the same method, which verifies the scalability of the soft-template strategy. This work provides a path for constructing ordered and tunable extrinsic porosity in COFs with greatly improved mass transfer efficiency and functional group accessibility.

Abstract Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values

Background/Purpose: Autonomic nervous system (ANS) disorders may occur in skeletal muscle disease, but the link between them has not been fully established. Studying the relationship between them may yield insights into the mechanisms and treatment of disease. This study aimed to explore the association between heart rate variability (HRV), sarcopenia, and subscales of sarcopenia (muscle mass, muscle strength, and physical mobility). Methods: 2514 community-dwelling older Chinese participants were included in this study. The Asian Working Group for Sarcopenia guidelines were used to define sarcopenia. HRV was measured by 90-s electrocardiogram RR interval data. All HRV parameters were transformed using natural logarithms. Multiple regression analysis and multivariate linear regression was performed using potential correlates. Results: The overall prevalence of sarcopenia was 15.1 % (18.5 % in males and 12.6 % in females). In the logistic regression analysis model, there was a significant association between log-transformed standard deviation of RR interval (lnSDNN) (OR = 0.736, p = 0.019), log-transformed coefficient of variation of RR intervals (lnCVRR) (OR = 0.751, p = 0.020), log-transformed low-frequency power (lnLF) (OR = 0.861, p = 0.008), log-transformed high-frequency power (lnHF) (OR = 0.864, p = 0.003) and sarcopenia in the general population after adjusting for age, sex, body mass index (BMI), daily activity levels, hypertension, heart disease and cardiac drugs. In addition, in multivariate linear regression, lnSDNN (β = 0.146, p = 0.001), lnCVRR (β = 0.120, p = 0.010), lnLF (β = 0.066, p = 0.002) and lnHF (β = 0.065, p

Societal Impact Statement With the rapid development of modern agriculture and its reliance on high‐yielding and genetically uniform varieties, many traditional agricultural systems are gradually being abandoned. The genetic diversity contained in landraces is crucial for modern eco‐agriculture. An indicator evaluation model combined with machine learning could help to locate and conserve these existing traditional agricultural systems, called agricultural heritage systems (AHS). Here, this method provided the first map of potential areas of Tea‐AHS in China. These results could help policymakers to confirm priorities and rationally allocate conservation resources based on the distribution status and endangerment of AHS. This could also help local people to receive additional support for the transfer of germplasm resources and indigenous knowledge. Summary Modern agriculture is overly dependent on high‐yielding and genetically uniform varieties, whereas traditional agricultural systems contain a large number of genetically diverse landraces and the indigenous knowledge associated with them. We call traditional agricultural systems that survive to the present‐day agricultural heritage systems (AHS). Under the impact of modernization, AHS are gradually disappearing. Identifying these systems is the first step towards conserving them, but the potential areas of AHS related to agro‐biodiversity are not yet clear. Using Chinese tea as an example, this paper provides the first universal method for identifying potential areas of AHS based on agro‐biodiversity and the first map of potential areas of Tea‐AHS in China. The map is constructed based on the maximum entropy model (Maxent) of tea germplasm resources and related indicator functions and has been validated by existing Tea‐AHS in China. The study identified 54 potential areas of Tea‐AHS. These potential areas are mainly concentrated in the southern region, in 15 provinces, including Anhui, Fujian, Guangdong, Yunnan, Guizhou, Guangxi, Hubei, and Hunan. Mangshi, Qimen County, and Chaisang District are among the high potential areas for Tea‐AHS and are the next priority for exploration and conservation work. We have verified the validity of the proposed method, which can help conserve the germplasm resources and traditional wisdom in the global AHS in a timely manner, and contribute to the development of modern and eco‐agriculture.

IntroductionThe rapid initiation of antiretroviral therapy (ART) and its impact on treatment outcomes have been a subject of global public health interest. However, the precise mechanisms underlying the effects of rapid ART initiation remain unclear.MethodsThis retrospective cohort study examined data from 1846 HIV-infected individuals in Jiulongpo District, Chongqing, China, spanning from 2016 to 2022. Logistic regression models and serial mediation analysis were used to explore the influence of rapid ART initiation on treatment outcomes and the role of medication adherence as a mediating factor.ResultsThe findings revealed a significant association between rapid ART initiation and reduced risk of viral failure (adjusted odds ratio [OR] = 0.320, 95% confidence interval [CI] = [0.161, 0.637]), as well as an increased likelihood of improved adherence (adjusted OR = 2.053, 95% CI = [1.226, 3.438]). Medication adherence was identified as a partial mediator in the relationship between rapid ART initiation and viral failure, explaining 10.5% of the total effect.DiscussionIn conclusion,rapid initiation of antiretroviral therapy was found to enhance treatment outcomes, emphasizing the importance of early adherence education. The study recommends early initiation of ART coupled with adherence education and psychological counseling for HIV-infected individuals.

Topological insulators (TI) are generating increasing interest as a new state of matter and due to the potential use of topologically- protected gapless surface states in spintronic devices and quantum computing. However, challenges such as high sensitivity to the atmosphere, the low surface-to-volume ratio, and the need for various material junctions currently limit their application. Here, a novel, natural and simple approach to the fabrication of volumetric TI heterostructures that can overcome these core challenges is presented, using the example of a Bi2Te3-Te eutectic composite. The proposed method based on directional solidification of eutectic composites, enables the formation of ensembles of parallel TI-other material heterojunctions through a self-organization process. It also offers control over the heterostructures’ dimensions/refinement. Electron microscopy techniques show that the heterostructure exhibits a lamellar/layered microstructure with atomically smooth Bi2Te3ǀǀTe interfaces. Angle-resolved photoelectron spectroscopy experiments confirm the existence of metallic surface states, while Kelvin probe force microscopy depicts the formed p-n junctions. The new degrees of freedom offered here, such as control of heterojunction chemical composition, packing density, and available fabrication techniques, may facilitate large-scale customized printing of topological devices.

Abstract Renal tubular epithelial cells (TECs) undergo an energy‐related metabolic shift from fatty acid oxidation to glycolysis during chronic kidney disease (CKD) progression. However, the mechanisms underlying this burst of glycolysis remain unclear. Herein, a new critical glycolysis regulator, the transcription factor forkhead box protein K1 (FOXK1) that is expressed in TECs during renal fibrosis and exhibits fibrogenic and metabolism‐rewiring capacities is reported. Genetic modification of the Foxk1 locus in TECs alters glycolytic metabolism and fibrotic lesions. A surge in the expression of a set of glycolysis‐related genes following FOXK1 protein activation contributes to the energy‐related metabolic shift. Nuclear‐translocated FOXK1 forms condensate through liquid‐liquid phase separation (LLPS) to drive the transcription of target genes. Core intrinsically disordered regions within FOXK1 protein are mapped and validated. A therapeutic strategy is explored by targeting the Foxk1 locus in a murine model of CKD by the renal subcapsular injection of a recombinant adeno‐associated virus 9 vector encoding Foxk1‐short hairpin RNA. In summary, the mechanism of a FOXK1‐mediated glycolytic burst in TECs, which involves the LLPS to enhance FOXK1 transcriptional activity is elucidated.

RET fusions were discovered in non-small cell lung cancer (NSCLC), and the efficacy of RET-targeted treatment in these patients has been previously established. However, patients with required resistance to RET-TKIs have limited treatment options. Herein, we describe a case of critical and advanced lung adenocarcinoma harboring RET fusion. Despite a significant response to Prasetinib previously, the patient developed refractory malignant pleural effusion after 24 months of treatment. He was treated simultaneously with intrapleural plus systemic Tislelizumab injection combined chemotherapy, thereby achieving an excellent clinical benefit maintaining control of pleural effusion for over 6 months. Hence, we would like to discuss intrapleural immunotherapy as an additional treatment method in refractory malignant pleural effusion while demonstrating good treatment tolerance.

We evaluated the effects of cottonseed meal protein hydrolysate (CPH) on the intestinal microbiota of yellow-feather broilers. We randomly divided 240 chicks into four groups with six replicates: basal diet with 0% (CON), 1% (LCPH), 3% (MCPH), or 5% (HCPH) CPH. The test lasted 63 days and included days 1–21, 22–42, and 43–63 phases. The ACE, Chao1, and Shannon indices in the MCPH and HCPH groups of 42-day-old broilers were higher than those in the CON group (p

Forecasting typhoon waves during typhoons is crucial. In this paper, the numerical wave model SWAN was enhanced through integration with two machine learning methods: the Back Propagation Neural Network and Random Forest. This integration facilitated the development of two distinct models, namely SWAN-BP and SWAN-Tree. Through correlation analysis, key input features were identified for the machine learning models. The forecasts from the SWAN model were subsequently utilized as inputs to enhance further wave prediction. These hybrid models were validated using data from Typhoon Doksuri (2023) and Typhoon Nesat (2017). The results indicated significant improvements in predicting typhoon-induced wave heights with both the SWAN-BP and SWAN-Tree models compared to the original SWAN model. Specifically, the SWAN-BP model demonstrated a 33% improvement in accuracy for the Typhoon Doksuri, whereas the SWAN-Tree model exhibited a 24% improvement. For Typhoon Nesat, the accuracy improvements were 23% for the SWAN-BP model and 21% for the SWAN-Tree model. These findings demonstrate that integrating wave numerical models with machine learning techniques can significantly enhance the predictive accuracy of numerical models. This approach offers a cost-effective means to improve the existing wave forecasting database. Traditionally, the direct use of meteorological and oceanographic data for typhoon wave prediction might be compromised by biases inherent in the numerical wave models. However, the SWAN-BP and SWAN-Tree models effectively reduce these biases, thereby providing more accurate and robust predictions. In conclusion, this paper enhances the predictive accuracy of the SWAN model and establishes a crucial foundation for more precise typhoon wave forecasting through the application of machine learning techniques.

Amubarvimab-romlusevimab is a commonly recommended antiviral treatment in China for adult patients with mild or moderate SARS-CoV-2 infections, especially for patients with a high risk factor for progression to severe COVID-19. However, its exact efficacy in patients with severe Covid-19 is not yet known.This is a single-center retrospective cohort study, in which we collected the general data, laboratory tests, radiological characteristics, viral conversion status, and prognosis of the disease from patients with COVID-19 hospitalized, from December 2022 to March 2023 in the Department of Critical Care Medicine. The amubarvimab-romlusevimab therapy can reduce the 28-day mortality (29.79 % vs 51.35 %, p = 0.02), and ICU mortality (29.79 % vs 55.41 %, p = 0.006) of severe COVID-19.A 1:1 PSM (Propensity Score Matching) was performed to reduce bias, in order to ensure the two groups were balanced and comparable. In the matched population (n = 47), there were no statistically significant differences between the mAbs (monoclonal antibody)group and the Non-antiviral group in 28-day, and thromboembolic events in COVID-19 patients. The 40-day survival analysis shows that mAbs therapy can improve patient prognosis (HR = 0.45, 95%CI = 0.26–0.76, p = 0.008). However, no significant intergroup difference in the 40-day cumulative viral conversion rate. In a univariate Cox regression analysis, The Amubarvimab - romlusevimab therapy(HR:0.464; CI:[0.252–0.853]; p:0.013) is a protective factor and CRP, PCT, PLT, Lactate, PT, PT-INR, and pt% level at admission were risk factors for clinical prognosis. After including the above covariates, Multifactorial COX regression shows that the Amubarvimab - romlusevimab therapy(HR:0.392; CI:[0.211–0.729]; p:0.003), CRP, Lactate and PT-INR at admission are independent factors for mortality of severe COVID-19. Based on the current data, we conclude that amubarvimab-romlusevimab therapy is beneficial for patients with severe COVID-19.

PurposeStatins may have a protective effect against osteoarthritis (including knee osteoarthritis and hip osteoarthritis); however, the link between statins and osteoarthritis risk is incompletely established. The aim of this study was to explore the relationship between statins and osteoarthritis risk through Mendelian randomization analysis using pooled information from a large population-wide genome-wide association study (GWAS).MethodsStatin-related single-nucleotide polymorphisms (SNPs) were obtained from FinnGen’s latest 9th edition database, and data on osteoarthritis, knee osteoarthritis, and hip osteoarthritis were acquired from the IEU OpenGWAS, the UK Biobank, and Arthritis Research UK Osteoarthritis Genetics (ArcOGEN) database, respectively. The inverse-variance weighting method is an important analysis method to estimate the causal effect. Weighted median method, simple median method, weighted median estimator method, and MR–Egger regression were employed to supplement the explanation. Odds ratio and 95%CI were used to evaluate the causal relationship among statins and the osteoarthritis risk, osteoarthritis in the knee, and osteoarthritis in the hip. Second, sensitivity analysis was carried out to validate the reliability of the results. Cochran’s Q test was employed to test heterogeneity, MR–Egger intercept was employed to test whether horizontal pleiotropy existed, and single-nucleotide polymorphisms with potential influence were determined by the one-method analysis.Results(1) The results of the inverse variance weighting method showed Gene prediction indicated that statins were associated with osteoarthritis (OR = 0.998, 95% CI: 0.996–0.999, P = 0.01) and knee osteoarthritis (OR = 0.964, 95% CI: knee (0.940–0.989, P = 0.005) and hip osteoarthritis risk were associated (OR = 0.928, 95% CI: 0.901–0.955, P = 4.28 × 10−7). (2) MR–Egger intercept analysis did not detect potential horizontal pleiotropy (osteoarthritis: P = 0.658; knee osteoarthritis: P = 0.600; and hip osteoarthritis: P = 0.141). (3) The findings provide evidence that statins reduce osteoarthritis risk, osteoarthritis in the knee, and osteoarthritis in the hip, as described in observational studies, and the specific mechanisms by which statins treat osteoarthritis require further investigation.ConclusionThe results of this study, at the genetic level, reveal a negative causal relationship between statins and osteoarthritis, and this causal relationship is also present in knee and hip osteoarthritis. This study provides evidence against the potential of statins in the treatment of osteoarthritis, prompting the clinical treatment of osteoarthritis to consider improving the start and compliance of statins in the future.

Understanding the evolution of the rural-urban interface (RUI) and its dynamic ecological consequences is of great theoretical and practical significance for urban-rural integration and management. In this study, Nanjing is taken as an example, and the evolution of the RUI in 1990, 2000, 2010, and 2020 and its effects on the ecological landscape structure and function are investigated. We first developed a discriminant matrix to identify the RUI during different periods based on land use maps and nighttime light data. The response of ecological landscape structure and function to the RUI evolution was analyzed using landscape metrics and ecosystem services value (ESV). The results show that the RUI experienced significant inter-transfer with rural and urban areas, and three evolution patterns were concluded, i.e., edge developing, rural industrializing, and outlying. The evolution of the RUI has led to landscape fragmentation and enhanced ecological land connectivity at the city scale. At the community/village scale, the shape of farmland became more regular with the evolution of the RUI. The transformation from rural to RUI and the maintenance of RUI would increase landscape fragmentation, richness, and the intertwining of artificial and natural land. The overall ecological function in terms of ESV usually decreased with the evolution of the RUI, except when the area of ecological land increased significantly. We believe that urban expansion, planning and protection policies, and industrial orientations are major factors facilitating the impacts of the RUI evolution on ecological landscape structure and function. At last, we gave suggestions of landscape management approaches and ecosystem services trade-off/synergy for the improvement of ecological landscape structure and function.

CO2 capture by microalgae is a feasible strategy to reduce CO2 emissions. However, large amounts of cell-free supernatant will be produced after microalgal harvesting, which may be harmful to the environment if it is disorderly discharged. In this study, Chlorella vulgaris (C. vulgaris) was cultivated under three common cultivation modes (autotrophic culture (AC), heterotrophic culture (HC) and mixotrophic culture (MC)), and the obtained supernatant was used as fertilizer to investigate its effect on the growth of lettuce. The biomass concentration of C. vulgaris cultivated under MC and HC was 3.25 and 2.59 times that of under AC, respectively. The contents of macronutrients in supernatant obtained from AC were higher than those of MC and HC. However, the contents of amino acids and hormones in supernatant obtained from MC and HC were higher than those of AC. The fresh shoot weight, fresh root weight and root length of lettuce treated with supernatant were significantly higher than that of control treatment. In addition, the contents of chlorophyll, soluble sugar and soluble protein in lettuce treated with supernatant were also higher than that of control treatment. However, the contents of nitrate in lettuce treated with supernatant was lower than that of control treatment. These results showed that the supernatant could promote the growth of lettuce and was a potential of fertilizer for crop planting.

BackgroundReactivate the T cell immunity by PD-1/PD-L1 checkpoint blockade is widely used in non-small cell lung cancer (NSCLC) patients, while the post-translational modification of Programmed death ligand-1 (PD-L1) is commonly existed in various cancer cells, thus increases the complexity and difficulty in therapy development. Ginsenoside Rg3 is an active component of traditional Chinese herb Ginseng with multiple pharmacological effects including immune regulation. However, the effect on the glycosylation of PD-L1 is unknown.MethodsNSCLC cell lines were tested for glycosylation of PD-L1, and the potential mechanisms were investigated. Tumor cell-T cell coculture experiment was conducted and the activation of T cells and cytotoxicity were measured by flow cytometry. In vivo xenograft mouse tumor model was used to investigate the effects of Rg3 on PD-L1-mediated immunosuppression and tumor growth.ResultsHere, we identified PD-L1 is widely N-linked glycosylated in NSCLC cell lines, while Rg3 could inhibit the glycosylation of PD-L1 by downregulating the EGFR signaling and further activate GSK3b-mediated degradation, thus resulted in reduced PD-L1 expression. Moreover, the inhibition of PD-L1 glycosylation promoted the activation and cytotoxicity of T cells under coculture condition. In addition, Rg3 could decrease the tumor volume and enhance anti-tumor T cell immunity as evidence by the upregulated expression of Granzyme B and perforin in CD8+T cells, along with elevated serum IL-2, IFN-g and TNF-a level in Rg3-treated mice.ConclusionsThese results suggest that Rg3 inhibits PD-L1 glycosylation and thus enhance anti-tumor immunity, which provide new therapeutic insight into drug discovery.

Modern medical understanding suggests that hyperproliferative skin diseases (HSDs) are complex syndromes characterized by localized hypertrophy or hyperplasia and infiltration of inflammatory cells. Various treatments, including systemic and topical pharmacotherapy, laser interventions, photodynamic therapy, and surgery, have been proposed for managing HSDs. However, challenges such as wound healing and recurrence after laser treatment have hindered the effectiveness of laser therapy. To overcome these challenges, we conducted a study combining laser therapy with cold atmospheric plasma (CAP) for the treatment of HSDs. Seven patients with different forms of HSDs, who had not responded well to conventional treatments, were enrolled in the study. These HSDs included cases of erythroplasia of Queyrat, pyoderma gangrenosum, keloids and hypertrophic scars, cellulitis, cutaneous lichen planus, and verruca vulgaris. Laser therapy was performed to remove the hyperplastic skin lesions, followed immediately by daily CAP treatment. The results were promising, with all patients successfully treated and no recurrence observed during the follow-up periods. The combined application of CAP and laser therapy proved to be an effective and complementary strategy for managing HSDs. This innovative approach provide evidence for addressing the limitation of laser therapy by utilizing CAP to promote wound healing and mitigate inflammatory responses.Chinese Clinical Trial Registry (ChiCTR2300069993).

BackgroundPrevious observational studies have reported certain causal relationships between factors such as smoking, alcohol consumption, obesity, physical activity, metabolic disorders, and the incidence of herpes zoster (HZ). However, there is controversy regarding the observed results across different studies. Our objective was to investigate the causal effects of these risk factors on the risk of herpes zoster through a Mendelian randomization analysis using two-sample bidirectional approaches.MethodsWe conducted two-sample bidirectional Mendelian randomization analyses to explore the causal relationships between different lifestyles, obesity assessment indices, metabolic indicators, and the risk of herpes zoster. All exposure and outcome data were sourced from publicly available data from genome-wide association studies.ResultsIn the inverse-variance weighted (IVW) analysis, body mass index (BMI) (OR: 1.160, 95% CI: 1.030–1.307, p = 0.014), Body fat percentage (BFP) (OR: 1.241, 95% CI: 1.050–1.467, p = 0.011), and whole body fat mass (WBFM) (OR: 1.199, 95% CI: 1.057–1.362, p = 0.005) exhibited positive associations with the risk of HZ. However, usual walking pace (UWP) (OR: 0.498, 95% CI: 0.254–0.976, p = 0.042) demonstrated a significant negative correlation with HZ risk. Other factors including alcohol intake frequency, smoking initiation, smoking status, insomnia, and sleep duration did not show significant causal relationships with HZ.ConclusionMendelian randomization studies revealed that BMI, BFP, and WBFM are risk factors for HZ. UWP showed a protective effect against HZ. These findings provide a straightforward method for evaluating future clinical practices aiming to develop personalized management strategies and assess high-risk populations for HZ.

Mucormycosis is an invasive fungal infection that can result in severe lung infections, with pulmonary mucormycosis (PM) being one of the most prevalent manifestations. Prompt diagnosis is crucial for patient survival, as PM often exhibits rapid clinical progression and carries a high fatality rate. Broncho-alveolar lavage fluid or endobronchial biopsy (EBB) has been commonly employed for diagnosing PM, although there is limited mention of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the literature. In this report, we present a case of PM in a patient with diabetes. While EBB did not yield evidence of Rhizopus infection, a definitive diagnosis was obtained through EBUS-TBNA. The patient underwent combination therapy, including oral medication, nebulization, and EBUS-guided intrafocal amphotericin B injection, which resulted in significant improvement following the failure of initial therapy with amphotericin B injection cholesterol sulfate complex. Our case highlights the potential of EBUS-TBNA not only for mediastinal lymphadenopathy but also for obtaining extraluminal lesion specimens. Furthermore, for patients with an inadequate response to mono-therapy and no access to surgical therapy, the addition of EBUS-guided intralesional amphotericin B injection to systemic intravenous therapy may yield unexpected effects.

Background: Gastric cancer (GC) is one of the most common malignant tumors in the world. It has become increasingly difficult to meet the needs of precision therapy using the existing molecular typing system. Therefore, developing a more effective molecular typing system for GC is urgent. Methods: In this study, 100 Chinese GC patients were included. Whole-exome sequencing (WES) and metabolomics analysis were performed to reveal the characteristics of genomic and metabolic changes. Results: In WES, nonsynonymous mutations accounted for the majority. Based on metabolomics, GC has been divided into three subtypes with distinct metabolic features. Importantly, we ultimately divided GC into four subtypes with different metabolic characteristics, genomic alterations, and clinical prognoses by incorporating biomics analysis. Conclusions: Integrating biological features, we constructed a novel molecular system for GC that was closely related to genetics and metabolism, providing new insights for further understanding the heterogeneity and formulating precise treatment strategies.

Background: Osteoarthritis (OA) is the most common form of joint diseases, with hallmark of cartilage degeneration. Recent studies have shown that the pathogenesis of OA is associated with chondrocyte necroptosis. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data to analyze necroptosis regulation in OA chondrocytes. We performed enrichment analysis, carried out experimental validation, constructed machine learning models, and docked drug molecules. Results: After least absolute shrinkage and selection operator (LASSO) algorithm screening, 4 hub genes (RIPK3, CYBB, HSP90AB1, and TRAF5) with diagnostic characteristics were obtained. Following the comparison of multiple models, the Bayesian model with an average area under curve (AUC) value of 0.944 was finally selected. We found that nimesulide exhibited strong binding affinity to CYBB and HSP90AB1, and experimentally verified that nimesulide reduced the expression of RIPK3 and CYBB, suggesting its potential as an inhibitor of chondrocyte necroptosis. Furthermore, scRNA-seq results showed that necroptosis in OA was significantly upregulated on regulatory chondrocytes (RegC) compared to other chondrocyte subtypes. Conclusions: The results indicate that nimesulide might be used to treat OA by inhibiting chondrocyte necroptosis through down-regulation of RIK3 and CYBB genes. This study reveals the role of chondrocyte necroptosis in OA, and suggests a potential therapeutic strategy by regulating necroptosis with nimesulide.

Summary: Ovarian cancer is a highly lethal gynecological malignancy, emphasizing the need for effective treatment strategies. This study investigated the synergistic effects of quercetin and paclitaxel on ovarian cancer. Using SKOV3 and A2780 cell lines, we found that the combined treatment significantly enhanced cell apoptosis and inhibited invasion and migration compared to individual treatments. Then, we identified 32 common targets between quercetin/paclitaxel and ovarian cancer, with 29 genes showing differential expression between normal ovarian tissue and ovarian tumor tissue. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that quercetin and paclitaxel modulated cancer-related pathways in ovarian cancer treatment. Mechanistic analysis further discovered that the synergistic effect was mediated by downregulating ERBB2 and BIRC5 and upregulating CASP3 expression. This study provides strong evidence that quercetin enhances the effectiveness of paclitaxel in treating ovarian cancer.

Utilizing satellite remote sensing for the assessment and temporal-spatial analysis of Chromophoric Dissolved Organic Matter (CDOM) is vital for overseeing lake water health and devising management plans. This study focused on the saline, turbid and arid Ebinur Lake, located in China’s northwestern region. The Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) model algorithms were compared to select the one with the highest accuracy. It combined Sentinel-2 remote sensing data and in situ measurement data for the quantitative inversion of CDOM. Monthly CDOM distribution maps were generated with a 10 m resolution for the non-frozen months of May to October from 2018 to 2022, followed by a comprehensive analysis of temporal trends. The primary conclusions are: (1) The XGBoost model yielded highly accurate CDOM estimates, with a training set coefficient of determination (R2) of 0.94, a Root Mean Square Error (RMSE) of 0.06 mg/L, Mean Absolute Percentage Error (MAPE) of 6.05 %, Relative Percent Difference (RPD) of 4.07; the test set demonstrated an R2 of 0.41 with an RMSE of 0.22 mg/L, MAPE of 22.74 %, RPD of 1.35; (2) Throughout the study period, the main lake portion displayed variable CDOM spatial patterns and trends. The inversion indicated higher CDOM concentrations in the central part than nearshore areas and decreasing CDOM in tandem with seasonable water-surface shrinkage. The findings offer hints for an accurate evaluation of water color parameters of Ebinur Lake and practical references for monitoring arid-region lake water quality via remote sensing.

Traditionally, leopards (Panthera pardus) and snow leopards (P. uncia) occupy distinct habitats. This study explored the coexistence of snow leopards and leopards within the Gaurishankar Conservation Area in Lapchi Valley, Nepal. Both leopard species are crucial for ecosystem stability as apex predators. Camera trapping data from 2018 to 2023 confirmed twenty species of wild mammals and two species of domesticated livestock in Lapchi Valley, where snow leopards have strong spatio-temporal overlap (Δ=0.74) with leopards. Snow leopards exhibited distinct temporal patterns before and after the leopards’ arrival in the study area. Generalized Linear Mixed Effect Models (GLMM) revealed seasonal and prey-type associations with leopard presence, highlighting the snow leopards' preference for cold season and wild prey. Leopards, however, did not show a significant seasonal preference. The findings highlight Lapchi Valley's ecological richness as well as the need for comprehensive conservation strategies. The record of spatial and temporal overlap between the leopards and snow leopards provides important insights into the behavioral dynamics of apex predators and the need for targeted biodiversity conservation in the face of changing ecosystems. The study emphasizes the valley's transboundary significance, calling for collaborative efforts between Nepal and China to help promote effective conservation management. Lapchi Valley's isolation, traditional and religious importance, and recent infrastructure developments further impact the conservation challenges.

Objective To explore the expression of USP9X in platelets and its effect on platelet function. Methods The expression of USP9X in human and mouse was evaluated by PCR and Western blot. Platelets from young and old mice were separated and prepared, and the expression of USP9X was detected. USP9X inhibitos were used to assess the regulation of USP9X in platelet function, including aggregation, ATP release and spreading. Platelet lysates were collected in different time points to evaluate the change of phosphorylation of Akt in USP9X inhibitors treated platelets. Results Both human and mouse platelets expressed USP9X. Compared to the young mice, the old mice showed significantly enhanced expression of USP9X(P

Biomedical magnesium (Mg) alloys have garnered significant attention because of their unique biodegradability, favorable biocompatibility, and suitable mechanical properties. The incorporation of rare earth (RE) elements, with their distinct physical and chemical properties, has greatly contributed to enhancing the mechanical performance, degradation behavior, and biological performance of biomedical Mg alloys. Currently, a series of RE-Mg alloys are being designed and investigated for orthopedic implants and cardiovascular stents, achieving substantial and encouraging research progress. In this work, a comprehensive summary of the state-of-the-art in biomedical RE-Mg alloys is provided. The physiological effects and design standards of RE elements in biomedical Mg alloys are discussed. Particularly, the degradation behavior and mechanical properties, including their underlying action are studied in-depth. Furthermore, the preparation techniques and current application status of RE-Mg alloys are reviewed. Finally, we address the ongoing challenges and propose future prospects to guide the development of high-performance biomedical Mg-RE alloys.

Abstract Battery remaining charging time (RCT) prediction can facilitate charging management and alleviate mileage anxiety for electric vehicles (EVs). Also, it is of great significance to improve EV users' experience. However, the RCT for a lithium-ion battery pack in EVs changes with temperature and other battery parameters. This study proposes an electrothermal model-based method to accurately predict battery RCT. Firstly, a characteristic battery cell is adopted to represent the battery pack, thus an equivalent circuit model (ECM) of the characteristic battery cell is established to describe the electrical behaviors of a battery pack. Secondly, an equivalent thermal model (ETM) of the battery pack is developed by considering the influence of ambient temperature, thermal management, and battery connectors in the battery pack to calculate the temperature which is then fed back to the ECM to realize electrothermal coupling. Finally, the RCT prediction method is proposed based on the electrothermal model and validated in the wide temperature range from − 20 ℃ to 45 ℃. The experimental results show that the prediction error of the RCT in the whole temperature range is less than 1.5%.

Abstract Purpose Assessing the clinical effectiveness of combining with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold to repair mid-distal defects in adjacent fingers. Methods From September 2012 to April 2022, 21 patients with 42 mid-distal defects of adjacent fingers underwent treatment using combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold. The flaps size ranged from 2.1 cm * 1.6 to 4.9 cm * 3.2 cm. Follow-up evaluations included assessing function, sensation, and appearance, etc. of the injured fingers and donor areas. Results All 42 flaps survived in 21 patients without any vascular crises, and the wounds healed in phase I. The mean follow-up time was 12.2 months (range 7–22 months). During follow-up, in injured fingers, according to the Michigan Hand Outcomes Questionnaire (MHOQ), the functional recovery and appearance were satisfactory; in Dargan Function Evaluation (DFE), the results were both “excellent” in fourteen patients, “excellent” and “good” in five patients, both “good” in one patient, “good” and “general” in one. In static two-point discrimination (2PD), the variation ranges from 4 to 9 mm in injured fingers and 6—10 mm in donor toes. Cold Intolerance Severity Score (CISS) is mild in all patients. The visual analogue score (VAS) showed no pain in the injured fingers and donor toes. No deformities or other complications were noted at the donor toes. According to Chinese Manchester Foot Pain and Disability Index (C-MFPDI), there was no morbidity on foot function in all donor areas. Conclusion The surgical procedure of combined with the first dorsal (plantar) metatarsal artery pedicle free bilobed flap with a cell scaffold for the repair of mid-distal adjacent fingers defect is highly satisfactory. This approach helps the injured fingers to achieve good function, sensibility and appearance, while also achieving satisfactory results in the donor toes.

Abstract Objectives Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. Methods A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. Results The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47–32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20–12.70, P = 0.024). Conclusions The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

Abstract Objective Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. Methods Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. Results Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944–0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014–1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551–0.852, P = 0.001) were also risk factors for the development of RLS. Conclusion Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.

The generation of vector beams using metasurfaces is crucial for the manipulation of light fields and has significant application potential, ranging from classical physics to quantum science. This paper introduces a novel dielectric metasurface composed of quarter-wave plate (QWP) meta-atoms, known as a QWP metasurface, designed to generate focused vector beams (VBs) of Bell-like states under right circularly polarized illumination. The propagation phase imparted on both the co- and cross-polarized components of the output field constructs hyperbolic and helical phase profiles with topological charge l p, whereas the Pancharatnam–Berry (PB) phase acts only on the cross-polarized component to construct another helical phase profile with topological charge l g. Thus, the co- and cross-polarized components form two orthogonal vector vortex (VV) modes with topological charges l p and l p + l g, respectively. When the parameter conditions are satisfied by matching the incident polarization chirality σ and topological charges l p and l g, the focused VBs of Bell-like states are generated by simultaneously manipulating the two VV modes, in contrast to existing QWP metasurfaces. The polarization states of the generated VBs are manipulated using the initial orientation angle θ 0 of the meta-atom. Overall, this research provides an innovative strategy for metasurface design, enhancing the functionality of metasurface devices for a broader range of application scenarios.

Abstract It is a long-standing scientific controversy to achieve anti-Kasha-type multiple emissions by tuning the structures at a molecular level. Although it is known that some conjugated structures have excitation-dependent multiple emissions, no all-benzenoid molecules have yet been reported, the emissions of which originate from different excited states. Herein, we report the design of two symmetry-breaking heterogeneous carbon bisnanohoops that in solution become multiple fluorescent emitters with unusual anti-Kasha characteristics. This phenomenon can be spectroscopically and theoretically explained and will find applications in a wide range of sensing and imaging technologies.

Abstract Moyamoya disease (MMD) remains a chronic progressive cerebrovascular disease with unknown etiology. A growing number of reports describe the development of MMD relevant to infection or autoimmune diseases. Identifying biomarkers of MMD is to understand the pathogenesis and development of novel targeted therapy and may be the key to improving the patient’s outcome. Here, we analyzed gene expression from two GEO databases. To identify the MMD biomarkers, the weighted gene co-expression network analysis (WGCNA) and the differential expression analyses were conducted to identify 266 key genes. The KEGG and GO analyses were then performed to construct the protein interaction (PPI) network. The three machine-learning algorithms of support vector machine-recursive feature elimination (SVM-RFE), random forest and least absolute shrinkage and selection operator (LASSO) were used to analyze the key genes and take intersection to construct MMD diagnosis based on the four core genes found (ACAN, FREM1, TOP2A and UCHL1), with highly accurate AUCs of 0.805, 0.903, 0.815, 0.826. Gene enrichment analysis illustrated that the MMD samples revealed quite a few differences in pathways like one carbon pool by folate, aminoacyl-tRNA biosynthesis, fat digestion and absorption and fructose and mannose metabolism. In addition, the immune infiltration profile demonstrated that ACAN expression was associated with mast cells resting, FREM1 expression was associated with T cells CD4 naive, TOP2A expression was associated with B cells memory, UCHL1 expression was associated with mast cells activated. Ultimately, the four key genes were verified by qPCR. Taken together, our study analyzed the diagnostic biomarkers and immune infiltration characteristics of MMD, which may shed light on the potential intervention targets of moyamoya disease patients