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Abstract Background Parkinson’s disease (PD) is a chronic neurodegenerative disorder that currently has no curable strategies. More and more evidence suggests that endoplasmic reticulum (ER) stress plays an essential role in PD pathogenesis. Periplaneta americana L. (P. americana) is a traditional Chinese medicine with diverse therapeutic properties. This study aims to investigate the neuroprotective effect and underlying mechanism of P. americana in in vitro and in vivo PD models. Methods The exposure of SH-SY5Y cells to 1-methyl-4-phenyl-pyridinium (MPP+) was used as the in vitro PD model. MTT assay, Hoechst staining, Calcein AM-PI staining and flow cytometry were performed to measure the cell viability and apoptosis. DCFH-DA and JC-1 assay were used to measure the intracellular ROS and mitochondrial membrane potential (Δψm), respectively. Western-blot and immunostaining were conducted to detect the expression of key molecules related with ER stress. For the in vivo PD model induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro-pyridine (MPTP), the motor function of mice was assessed by behavioral tests, the level of TH was examined by western-blot and immunostaining, the expression of key molecules related with ER stress was measured by western-blot. Results Periplaneta americana ethanol extract (PAE) concentration-dependently inhibited MPP+-induced cell loss and increased cell viability. PAE also remarkably attenuated ROS accumulation, the decline of Δψm as well as the excessive ER stress. The neuroprotective effects of PAE could be blocked by ROS inducer trimethylamine N-Oxide or ER stress activator tunicaymycin, while the antioxidant N-Acetyl-L-cysteine or ER stress inhibitor sodium 4-phenylbutyrate mimicked the effects of PAE. Furthermore, we found that PAE could activate AKT/GSK3β/β-catenin pathway. The effect of PAE on ROS production, Δψm and ER stress was blocked by AKT inhibitor MK-2206. In in vivo model, PAE significantly improved motor function, prevented dopaminergic neuronal loss and attenuated ER stress in substantia nigra and striatum of MPTP-treated mice. Similarly, the effects of PAE on MPTP-treated mice were also abolished by MK-2206. Conclusions Our results suggest that P. americana exerts neuroprotective effects through inhibiting ER stress via AKT-dependent pathway. Periplaneta americana may represent a promising therapeutic agent for PD treatment and is worthy of further being exploited.

Abstract Background Drug-target interaction (DTI) prediction plays a pivotal role in drug discovery and drug repositioning, enabling the identification of potential drug candidates. However, most previous approaches often do not fully utilize the complementary relationships among multiple biological networks, which limits their ability to learn more consistent representations. Additionally, the selection strategy of negative samples significantly affects the performance of contrastive learning methods. Results In this study, we propose CCL-ASPS, a novel deep learning model that incorporates Collaborative Contrastive Learning (CCL) and Adaptive Self-Paced Sampling strategy (ASPS) for drug-target interaction prediction. CCL-ASPS leverages multiple networks to learn the fused embeddings of drugs and targets, ensuring their consistent representations from individual networks. Furthermore, ASPS dynamically selects more informative negative sample pairs for contrastive learning. Experiment results on the established dataset demonstrate that CCL-ASPS achieves significant improvements compared to current state-of-the-art methods. Moreover, ablation experiments confirm the contributions of the proposed CCL and ASPS strategies. Conclusions By integrating Collaborative Contrastive Learning and Adaptive Self-Paced Sampling, the proposed CCL-ASPS effectively addresses the limitations of previous methods. This study demonstrates that CCL-ASPS achieves notable improvements in DTI predictive performance compared to current state-of-the-art approaches. The case study and cold start experiments further illustrate the capability of CCL-ASPS to effectively predict previously unknown DTI, potentially facilitating the identification of new drug-target interactions.

Abstract Purpose To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity. Methods The aqueous humor samples were collected from 16 eyes with subretinal fibrosis due to nAMD (SRFi group), 33 eyes with nAMD without subretinal fibrosis (nAMD group) and 28 eyes with cataract patients (control group). Clinical samples were analyzed for 5 cytokines,including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), platelet-derived growth factor-BB (PDGF-BB). Results Aqueous humor cytokines VEGF and bFGF were significantly higher in nAMD patients than controls (all P

Abstract Background Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT). Methods In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III–IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin β1 (ITGB1) expression was analyzed as a biomarker for efficacy. Results After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT. Conclusions This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting. Trial registration www.ClinicalTrials.gov . NCT02923258 (date of registration: October 4, 2016)

With the implementation of the overall national security concept, data security governance rises to a new strategic height. In this paper, for the incomplete status quo of digital service platforms, third-party testing organizations and government regulators in the construction of digital security, an evolutionary game model based on the above three parties is constructed. The model examines the strategic decision-making process, behavioral influences, and evolutionary stability of the three players, and is simulated and analyzed using MATLAB. The results show that the evolutionary system will reach the ideal stable state E(1,1,1), which corresponds to the combination of strategies: providing high-quality products, refusing to rent-seeking, and strict regulation. In order to guide the evolving system to reach the ideal stable state, this study puts forward some policy recommendations in terms of establishing a data security assessment mechanism, collaborative technology governance, and optimizing the governance architecture.

Abstract Background Combining conventional radiomics models with deep learning features can result in superior performance in predicting the prognosis of patients with tumors; however, this approach has never been evaluated for the prediction of metachronous distant metastasis (MDM) among patients with retroperitoneal leiomyosarcoma (RLS). Thus, the purpose of this study was to develop and validate a preoperative contrast-enhanced computed tomography (CECT)-based deep learning radiomics model for predicting the occurrence of MDM in patients with RLS undergoing complete surgical resection. Methods A total of 179 patients who had undergone surgery for the treatment of histologically confirmed RLS were retrospectively recruited from two tertiary sarcoma centers. Semantic segmentation features derived from a convolutional neural network deep learning model as well as conventional hand-crafted radiomics features were extracted from preoperative three-phase CECT images to quantify the sarcoma phenotypes. A conventional radiomics signature (RS) and a deep learning radiomics signature (DLRS) that incorporated hand-crafted radiomics and deep learning features were developed to predict the risk of MDM. Additionally, a deep learning radiomics nomogram (DLRN) was established to evaluate the incremental prognostic significance of the DLRS in combination with clinico-radiological predictors. Results The comparison of the area under the curve (AUC) values in the external validation set, as determined by the DeLong test, demonstrated that the integrated DLRN, DLRS, and RS models all exhibited superior predictive performance compared with that of the clinical model (AUC 0.786 [95% confidence interval 0.649–0.923] vs. 0.822 [0.692–0.952] vs. 0.733 [0.573–0.892] vs. 0.511 [0.359–0.662]; both P

In order to study the vibration characteristics of shearer’s spiral drum under various occurrence conditions，the coal-rock contact model was optimized by taking the MG2×55/250–BWD thin seam shearer as the engineering object, and discrete element model of the coal wall under various cutting conditions similar to the actual occurrence conditions were established. Combined with DEM–MFBD (Discrete Element Method-Multi Flexible Body Dynamics) two-way coupling numerical simulation method, the two-way coupling simulation platform of the rigid-flexible coupling virtual prototype model of the shearer cutting section and the discrete element model of the coal wall was built. Through simulation, the cutting process of the spiral drum under different coal wall working conditions was obtained, and the variation law of the vibration characteristics of the spiral drum under different occurrence conditions was analyzed. The results show that: during the cutting process, the spiral drum vibrates to different degrees in three directions, of which the vibration acceleration in the cutting resistance direction is the largest, the vibration acceleration in the traction resistance direction is the second, and the vibration acceleration in the lateral force direction is the smallest. With the increase of the hardness of the gangue and the proportion of the number of layers in the model, the vibration intensity of the spiral drum during the cutting process continues to increase, and the difference between the effective values of the maximum vibration acceleration reaches 4 403.149 mm/s2. The short-time Fourier transform was used to convert one-dimensional vibration signal into two-dimensional time-frequency spectrum image, and the characteristics of vibration information change under different working conditions were well preserved in time-frequency domain. The feature sample effect of time-frequency spectrum image is better than that of time-domain one-dimensional signal curve under various working conditions. The information such as the location, scope and shape of feature cluster of dominant frequency energy have obvious differences. Even if the number of rock parting is different, the distribution form of energy characteristics in the time-frequency spectrum image is also significantly different under complex working conditions where there are differences in the firmness coefficient of the rock parting. Through vibration modal analysis, it is found that with the increase of the hardness of the gangue in the coal wall, the deformation of each part changes, and the change of the pick part is the strongest. Building a vibration signal testing experimental platform for shearer based on similarity theory. The cutting process of spiral drum under different working conditions was tested experimentally. By tracking the vibration state of the spiral drum, it is found that the vibration change law is consistent with the results of the two-way coupling numerical simulation. The error between the effective value of the vibration acceleration of the spiral drum obtained by the DEM–MFBD numerical simulation method and the experimental data inferred based on similarity ratio is smaller than the error between the DEM discrete element numerical simulation method and the experimental data, which verifies the accuracy of the DEM–MFBD numerical simulation method. The research results are of great significance for the working reliability of the lifting spiral drum, and also provide a new method for obtaining data signals during the construction of the coal and rock cutting state recognition system for "unmanned" intelligent mining.

Postoperative delayed gastric emptying is a prevalent complication following surgical procedures, imposing heavy physical and financial burdens on patients. However, current treatment options remain suboptimal. In recent years, an increasing number of studies have highlighted that the gut microbiota and its metabolites are closely associated with postoperative complications. Various factors can disrupt the gut microbiome after surgery. This review discusses the potential mechanisms by which the gut microbiota and their metabolites may contribute to the pathogenesis of postoperative delayed gastric emptying. However, the current knowledge base is limited in terms of fully understanding the exact mechanisms involved. It is therefore evident that further research is required to fully elucidate the role of the gut microbiome in postoperative delayed gastric emptying, with the aim of uncovering new possibilities for preventive measures and therapeutic treatments.

Microscopic defects in flip chips, originating from manufacturing, significantly affect performance and longevity. Post-fabrication sampling methods ensure product functionality but lack in-line defect monitoring to enhance chip yield and lifespan in real-time. This study introduces a photoacoustic remote sensing (PARS) system for in-line imaging and defect recognition during flip-chip fabrication. We first propose a real-time PARS imaging method based on continuous acquisition combined with parallel processing image reconstruction to achieve real-time imaging during the scanning of flip-chip samples, reducing reconstruction time from an average of approximately 1134 ms to 38 ms. Subsequently, we propose improved YOLOv7 with space-to-depth block (IYOLOv7-SPD), an enhanced deep learning defect recognition method, for accurate in-line recognition and localization of microscopic defects during the PARS real-time imaging process. The experimental results validate the viability of the proposed system for enhancing the lifespan and yield of flip-chip products in chip manufacturing facilities.

The diversity and practicability of terahertz metamaterials have experienced rapid development in the past decade due to the increasing demand for various devices. This topic has attracted significant interest from researchers. Among the key functional devices in terahertz metamaterial systems, the active control ability of terahertz metamaterials is highly valuable and captivating. This implies that the electromagnetic properties of metamaterials can be modulated over a wide dynamic range by external stimuli. This review categorizes the different types of tunable terahertz metamaterials based on the external stimuli to which they respond, namely, mechanical modulation, electrical modulation, magnetic modulation, and optical modulation. Mechanically modulated devices offer simple yet efficient modulation, while electrical and magnetic modulation provide effective active modulation through electrical mechanisms. Optical modulation, in contrast, focuses on incorporating various materials to achieve active modulation.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder with no permanent cure that affects the quality of life due to trismus. Computational pharmacology has accelerated the discovery of drug candidates for the treatment of incurable diseases. The present study aimed to screen the compounds of the miracle herb Centella asiatica with drug-likeness properties based on the absorption, distribution, metabolism, and excretion (ADME) properties. The pharmacological actions of these screened compounds against OSMF were identified by network pharmacology, gene ontology, pathway enrichment analysis, molecular docking, and simulation. Fifteen drug-like ligands were identified after virtual screening viz; asiatic acid, kaempferol, quercetin, luteolin, apigenin, bayogenin, gallic acid, isothankunic acid, madecassic acid, madasiatic acid, arjunolic acid, terminolic acid, catechin, epicatechin, and nobiletin. 850 potential targets were predicted for the ligands, which were analyzed against 354 proteins associated with OSMF. Compound pathway analysis and disease pathway analysis identified 53 common proteins. The GO enrichment analysis identified 472 biological process terms, 76 molecular function terms, and 44 cellular component terms. Pathway enrichment analysis predicted 142 KEGG pathways, 35 Biocarta pathways, and 236 Reactome pathways for the target proteins. The analysis revealed that the herb targets crucial events of fibrosis such as inflammation, oxidative stress, apoptosis, collagen deposition, and epithelial-mesenchymal transition. The common 53 proteins were used for protein-protein interaction (PPI) network analysis, which revealed 4 key proteins interacting with the phytocompounds viz; transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic-3 (SMAD-3), mitogen-activated protein kinase-1 (MAPK-1) and proto-oncogene tyrosine-protein kinase (SRC). Molecular docking revealed that all ligands had a good binding affinity to the target proteins. Bayogenin had the highest binding affinity towards MAPK-1 (−9.7 kcal/mol), followed by isothankunic acid towards SRC protein (−9.3 kcal/mol). Madasiatic acid had the highest binding affinity to SMAD-3 (−7.6 kcal/mol) and TGF-β1 (−7.1 kcal/mol). Molecular dynamics simulation demonstrated stable ligand protein interactions of bayogenin and MAPK complex, isothankunic acid and SRC complex. This in silico study is the first to identify potential phytochemicals present in Centella asiatica and their target molecules, which might be responsible for reversing OSMF.

ABSTRACT African swine fever (ASF) is a highly fatal viral disease that poses a significant threat to domestic pigs and wild boars globally. In our study, we aimed to explore the potential of a multiplexed CRISPR-Cas system in suppressing ASFV replication and infection. By engineering CRISPR-Cas systems to target nine specific loci within the ASFV genome, we observed a substantial reduction in viral replication in vitro. This reduction was achieved through the concerted action of both Type II and Type III RNA polymerase-guided gRNA expression. To further evaluate its anti-viral function in vivo, we developed a pig strain expressing the multiplexable CRISPR-Cas-gRNA via germline genome editing. These transgenic pigs exhibited normal health with continuous expression of the CRISPR-Cas-gRNA system, and a subset displayed latent viral replication and delayed infection. However, the CRISPR-Cas9-engineered pigs did not exhibit a survival advantage upon exposure to ASFV. To our knowledge, this study represents the first instance of a living organism engineered via germline editing to assess resistance to ASFV infection using a CRISPR-Cas system. Our findings contribute valuable insights to guide the future design of enhanced viral immunity strategies.IMPORTANCEASFV is currently a devastating disease with no effective vaccine or treatment available. Our study introduces a multiplexed CRISPR-Cas system targeting nine specific loci in the ASFV genome. This innovative approach successfully inhibits ASFV replication in vitro, and we have successfully engineered pig strains to express this anti-ASFV CRISPR-Cas system constitutively. Despite not observing survival advantages in these transgenic pigs upon ASFV challenges, we did note a delay in infection in some cases. To the best of our knowledge, this study constitutes the first example of a germline-edited animal with an anti-virus CRISPR-Cas system. These findings contribute to the advancement of future anti-viral strategies and the optimization of viral immunity technologies.

Ubiquitination is a key mechanism for post-translational protein modification, affecting protein localization, metabolism, degradation and various cellular physiological processes. Dysregulation of ubiquitination is associated with the pathogenesis of various diseases, such as tumors and cardiovascular diseases, making it a primary area of interest in biochemical research and drug development endeavors. E3 ubiquitin ligases play a pivotal role in modulating the ubiquitination of substrate proteins through their unique recognition functions. TRIM31, a member of the TRIM family of E3 ubiquitin ligases, is aberrantly expressed in different pathophysiological conditions. The biological function of TRIM31 is associated with the occurrence and development of diverse diseases. TRIM31 has been demonstrated to inhibit inflammation by promoting ubiquitin-proteasome-mediated degradation of the sensing protein NLRP3 in the inflammasome. TRIM31 mediates ubiquitination of MAVS, inducing the formation of prion-like aggregates, and triggering innate antiviral immune responses. TRIM31 is also implicated in tumor pathophysiology through its ability to promote ubiquitination of the tumor suppressor protein p53. These findings indicate that TRIM31 is a potential therapeutic target, and subsequent in-depth research of TRIM31 is anticipated to provide information on its clinical application in therapy.

Performing arts education has been significantly affected by the COVID-19 pandemic crisis around the world since early 2020. Educators had to adapt the classes with remote learning when face-to-face instruction had been suspended during the pandemic. Although frustrations and confusion continued to abound with the implementation of new pedagogies, online teaching, and learning spurred new practices, innovative ideas, and breakthroughs. Some performing arts educators took this opportunity to explore new skills and strategies and provided performing arts students with more impactful learning experiences. Presently, with the COVID-19 pandemic gradually showing a sign of easing, many Hong Kong schools have returned to in-person instruction. Meanwhile, the impactful learning feedback from students triggered calls for redesigning the pedagogy of performing arts education. This study placed the impact of COVID-19 on performing arts education into context and drilled down into the delivery of performing arts education in the post-pandemic era. This study reviewed teaching and learning experiences of performing arts education, with the following three research questions addressed: (a) What is the correlation between performing arts students’ academic traits and their proficiency in utilizing technology during the COVID-19 pandemic? (b) What are the influential factors impacting the hybrid learning experience and outcomes of performing arts students during the COVID-19 pandemic? (c) What are the anticipated expectations of performing arts students regarding future models of arts education? Furthermore, practical solutions and insights for performing arts educational delivery in the post-pandemic era are provided in this study.

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is characterized by skin pruritus, elevated liver enzymes, and increased serum total bile acids. Several previous studies have revealed that the fasting and ejection volumes of the gallbladder in cholestasis of pregnancy are greater than those in normal pregnancy. The goal of this study was to explore the gallbladder volume and evaluate the diagnostic and prognostic value of ultrasound in ICP. Methods We prospectively recruited a cohort of 60 ICP patients at the First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, China from January 2020 to December 2021 and compared their data with those from healthy pregnant women (n = 60). The gallbladder volume was evaluated by real-time ultrasound examination after overnight fasting and at 30, 60, 120, and 180 min after a liquid test meal of 200 mL, and the ejection fraction was calculated. Continuous data between two groups were compared by Student’s t test. Differences were considered significant for p

Abstract Background Celastrol has been revealed to exhibit anticancer pharmacological activity, however, the molecular mechanisms of celastrol involved in pancreatic cancer remain to be further elucidated. The present study was to illustrate whether celastrol suppresses pancreatic cancer through modulating RNA m6A modification. Methods Effect of celastrol treatment on the malignant phenotypes of pancreatic cancer cells was evaluated by CCK-8 assay, EdU assay, colony formation assay, flow cytometry analysis and subcutaneous xenograft experiments. RNA sequencing (RNA-seq) analysis was carried out to analyze the genes differentially expressed in celastrol-treated pancreatic cancer cells. RT-qPCR, Western blotting and immunohistochemistry were employed to evaluate the expression of the indicated genes. RNA dot blot and quantification of total RNA m6A modification assays, MeRIP-qPCR assay, RIP-qPCR assay, RNA stability and protein stability assays were applied to evaluate the regulatory mechanism of celastrol treatment in pancreatic cancer cells. Results We demonstrated that celastrol suppressed cell proliferation and induced cell cycle arrest and apoptosis of pancreatic cancer cells in vitro, and decreased tumor growth in vivo. Specifically, Bcl-2, Claspin, METTL3 and YTHDF3 were identified as the potential targets of celastrol treatment in pancreatic cancer cells. Moreover, our results indicated that celastrol treatment downregulated METTL3 and decreased m6A levels of Claspin and Bcl-2 mRNA, leading to the degradation of Claspin and Bcl-2 mRNA in pancreatic cancer cells. Furthermore, we revealed that celastrol treatment downregulated Claspin and Bcl-2, at least in part, in an m6A-YTHDF3-mediated manner in pancreatic cancer cells. Conclusion Our study highlighted a novel mechanism underlying celastrol-induced cellular proliferation inhibition and apoptosis in pancreatic cancer cells via m6A-YTHDF3-mediated downregulation of Claspin and Bcl-2.

Abstract Background Diabetic cardiomyopathy, a distinctive complication of diabetes mellitus, has been correlated with the presence of intracellular lipid deposits. However, the intricate molecular mechanisms governing the aberrant accumulation of lipid droplets within cardiomyocytes remain to be comprehensively elucidated. Methods Both obese diabetic (db/db) mice and HL‐1 cells treated with 200 μmol/L palmitate and 200 μmol/L oleate were used to simulate type 2 diabetes conditions. Transmission electron microscopy is employed to assess the size and quantity of lipid droplets in the mouse hearts. Transcriptomics analysis was utilized to interrogate mRNA levels. Lipidomics and ubiquitinomics were employed to explore the lipid composition alterations and proteins participating in ubiquitin‐mediated degradation in mice. Clinical data were collected from patients with diabetes‐associated cardiomyopathy and healthy controls. Western blot analysis was conducted to assess the levels of proteins linked to lipid metabolism, and the biotin‐switch assay was employed to quantify protein cysteine S‐sulfhydration levels. Results The administration of H2S donor, NaHS, effectively restored hydrogen sulfide levels in both the cardiac tissue and plasma of db/db mice (+7%, P

Introduction: The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances in Therapeutic LNPs: LNPs, composed of ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, facilitate efficient cellular uptake and cytosolic release of mRNA while mitigating degradation by nucleases. However, as synthetic entities, LNPs face challenges that alter their therapeutic efficacy and safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides a comprehensive overview of the latest advancements in LNP research, focusing on preclinical safety assessments encompassing toxicity, reactogenicity, and immunogenicity. Summary and Outlook: Additionally, it outlines potential strategies for addressing these challenges and offers insights into future research directions for enhancing the application of LNPs in mRNA therapeutics.

Proteins perform different biological functions through binding with various molecules which are mediated by a few key residues and accurate prediction of such protein binding residues (PBRs) is crucial for understanding cellular processes and for designing new drugs. Many computational prediction approaches have been proposed to identify PBRs with sequence-based features. However, these approaches face two main challenges: (1) these methods only concatenate residue feature vectors with a simple sliding window strategy, and (2) it is challenging to find a uniform sliding window size suitable for learning embeddings across different types of PBRs. In this study, we propose one novel framework that could apply multiple types of PBRs Prediciton task through Multi-scale Sequence-based Feature Fusion (PMSFF) strategy. Firstly, PMSFF employs a pre-trained language model named ProtT5, to encode amino acid residues in protein sequences. Then, it generates multi-scale residue embeddings by applying multi-size windows to capture effective neighboring residues and multi-size kernels to learn information across different scales. Additionally, the proposed model treats protein sequences as sentences, employing a bidirectional GRU to learn global context. We also collect benchmark datasets encompassing various PBRs types and evaluate our PMSFF approach to these datasets. Compared with state-of-the-art methods, PMSFF demonstrates superior performance on most PBRs prediction tasks.

The paper presents a vision-based obstacle avoidance strategy for lightweight self-driving cars that can be run on a CPU-only device using a single RGB-D camera. The method consists of two steps: visual perception and path planning. The visual perception part uses ORBSLAM3 enhanced with optical flow to estimate the car’s poses and extract rich texture information from the scene. In the path planning phase, the proposed method employs a method combining a control Lyapunov function and control barrier function in the form of a quadratic program (CLF-CBF-QP) together with an obstacle shape reconstruction process (SRP) to plan safe and stable trajectories. To validate the performance and robustness of the proposed method, simulation experiments were conducted with a car in various complex indoor environments using the Gazebo simulation environment. The proposed method can effectively avoid obstacles in the scenes. The proposed algorithm outperforms benchmark algorithms in achieving more stable and shorter trajectories across multiple simulated scenes.

Concrete slump, a crucial indicator of fluidity, directly affects the pumpability and construction efficiency of concrete. Conventionally, concrete slumps are assessed through multiple test iterations conducted by skilled professionals to obtain accurate results. In this study, a predictive model was established to predict concrete slumps directly based on concrete mix proportions, thereby mitigating labor and time costs. An open-source dataset was used in this study. The selected water-cement ratio ranged from 0.29 to 0.66. Cement, slag, fly ash, water, superplasticizer, coarse aggregate, and fine aggregate were employed as input parameters. Furthermore, the performances of a variety of algorithms in predicting concrete slumps were analyzed and compared. The algorithms included SVM, KNN, Extra-Trees, Gradient Boosting, Decision Tree, Elastic Net, Lasso, Ridge, Random Forest, Bagging, AdaBoost, and XGBoost. Through a comprehensive comparison of the prediction performance of these models, AdaBoost, Bagging, Extra-Trees, and Random Forest were adopted as base models. Moreover, the SVM algorithm optimized using Differential Evolution was employed as a secondary model to construct an enhanced integrated prediction model. The final prediction model boasts an MSE of 2.099984, MAE of 1.225597, RMSE of 1.449132, and R2 of 0.970418. Compared to conventional prediction models, the proposed model has the potential to substantially improve prediction performance.

In this work, the formation of carbon-based nanomaterials–fulvic acid (CNMs-FA) composites and their capacities for the adsorption and photodegradation of typical organic contaminants in aqueous solutions were investigated. The results suggested that the formation of CNMs-FA composites was dominated by adsorbing FA on CNMs via the physisorption process, which fit the pseudo-first-order kinetic model and the Langmuir isotherm model. The formed CNMs-FA composites were characterized by using the Brunauer–Emmett–Teller, scanning electron microscopy, and infrared spectroscopy techniques and further applied for examining their effects on the adsorption and photodegradation of selected organic contaminants in aqueous solutions. The adsorption of organic contaminants on CNMs-FA composites is mainly involved in hydrogen bonding and electrostatic interactions between organic contaminants and FA species adhering to CNMs. In addition, the CNMs-FA composites are able to promote the photosensitive degradation of organic contaminants due to the photogenerated reactive species including ROS and CNMs-3FA* under sunlight irradiation. This study provided a deeper and more comprehensive understanding of the environmental behavior of CNMs in real natural surface water and clarified the underlying mechanisms. HIGHLIGHTS Carbon-based nanomaterials (CNMs) preferentially adsorb fulvic acid to form CNMs-FA in environmental water.; Adsorption of FA on CNMs fits pseudo-first-order kinetic and Langmuir isotherm models.; CNMs-FA can adsorb organic pollutants via hydrogen bonding and electrostatic interactions.; CNMs-FA promotes the photodegradation of organic pollutants under sunlight irradiation.;

Abstract Excessive ROS accumulation contributes to cardiac injury in type 2 diabetes mellitus. Hydrogen sulfide (H2S) is a vital endogenous gasotransmitter to alleviate cardiac damage in diabetic cardiomyopathy (DCM). However, the underlying mechanisms remain unclear. In this study, we investigated the effects of NaHS administration in db/db mice via intraperitoneal injection for 20 weeks and the treatment of high glucose (HG), palmitate (PA) and NaHS in HL-1 cardiomyocytes for 48 h, respectively. H2S levels were decreased in hearts of db/db mice and HL-1 cardiomyocytes exposed to HG and PA, which were restored by NaHS. Exogenous H2S activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4)/glutathione (GSH) pathway, suppressed ferroptosis and mitigated mitochondrial apoptosis in db/db mice. However, these effects were abrogated after Nrf2 knockdown. NaHS treatment elevated the ubiquitination level of Kelch-like ECH-associated protein (Keap1) by preserving its E3 ligase synoviolin (Syvn1), resulting in Nrf2 nuclear translocation. H2S facilitated the sulfhydration of Syvn1-cys115 site, a post-translational modification. Transfecting Syvn1 C115A in cardiomyocytes exposed to HG and PA partially attenuated the effects of NaHS on Nrf2 and cell death. Our findings suggest that exogenous H2S regulates Nrf2/GPx4/GSH pathway by promoting the Syvn1-Keap1 interaction to reduce ferroptosis and mitochondrial apoptosis in DCM.

Abstract Background Activated sludge (AS) systems in wastewater treatment plants (WWTPs) harbor enormous viruses that regulate microbial metabolism and nutrient cycling, significantly influencing the stability of AS systems. However, our knowledge about the diversity of viral taxonomic groups and functional traits in global AS systems is still limited. To address this gap, we investigated the global diversity and biogeography of DNA viral communities in AS systems using 85,114 viral operational taxonomic units (vOTUs) recovered from 144 AS samples collected across 54 WWTPs from 13 different countries. Results AS viral communities and their functional traits exhibited distance-decay relationship (DDR) at the global scale and latitudinal diversity gradient (LDG) from equator to mid-latitude. Furthermore, it was observed that AS viral community and functional gene structures were largely driven by the geographic factors and wastewater types, of which the geographic factors were more important. Carrying and disseminating auxiliary metabolic genes (AMGs) associated with the degradation of polysaccharides, sulfate reduction, denitrification, and organic phosphoester hydrolysis, as well as the lysis of crucial functional microbes that govern biogeochemical cycles were two major ways by which viruses could regulate AS functions. It was worth noting that our study revealed a high abundance of antibiotic resistance genes (ARGs) in viral genomes, suggesting that viruses were key reservoirs of ARGs in AS systems. Conclusions Our results demonstrated the highly diverse taxonomic groups and functional traits of viruses in AS systems. Viral lysis of host microbes and virus-mediated HGT can regulate the biogeochemical and nutrient cycles, thus affecting the performance of AS systems. These findings provide important insights into the viral diversity, function, and ecology in AS systems on a global scale. Video Abstract

In response to the analysis of the functional status of forearm blood vessels, this paper fully considers the orientation of the vascular skeleton and the geometric characteristics of blood vessels and proposes a blood vessel width calculation algorithm based on the radius estimation of the tangent circle (RETC) in forearm near-infrared images. First, the initial infrared image obtained by the infrared camera is preprocessed by image cropping, contrast stretching, denoising, enhancement, and initial segmentation. Second, the Zhang–Suen refinement algorithm is used to extract the vascular skeleton. Third, the Canny edge detection method is used to perform vascular edge detection. Finally, a RETC algorithm is developed to calculate the vessel width. This paper evaluates the accuracy of the proposed RETC algorithm, and experimental results show that the mean absolute error between the vessel width obtained by our algorithm and the reference vessel width is as low as 0.36, with a variance of only 0.10, which can be significantly reduced compared to traditional calculation measurements.

On 22 May 2021, an earthquake (98.3° E and 34.59° N) struck Maduo town in Qinghai province, occurring along a relatively obscure secondary fault within the block. We utilized 105 archived Sentinel-1A/B acquisitions to investigate the coseismic deformation and the evolution of postseismic displacements in both the temporal and spatial domains, as well as the associated dynamic mechanisms of the 2021 Maduo earthquake. The interference fringes and coseismic deformation revealed that the primary feature of this event was the rupture along a left-lateral strike-slip fault. The released seismic moment was close to 1.88 × 1020 N·m, which is equivalent to an Mw 7.45 event. Simultaneously, the maximum coseismic slip reached approximately 4 m along the fault plane. The evolution of postseismic displacements in both the temporal and spatial domains over 450 days following the mainshock was further analyzed to explore the underlying physical mechanisms. Generally, the patterns of coseismic slip and afterslip were similar, although the postseismic displacements decayed rapidly over time. The modeled afterslip downdip of the coseismic rupture (at depths of 15–40 km) effectively explains the postseismic deformation, with a released moment estimated at 4.57 × 1019 N·m (corresponding to Mw 7.04). Additionally, we found that regions with high coseismic slip tend to exhibit weak seismicity, and that afterslip and aftershocks are likely driven by each other. Finally, we estimated the Coulomb Failure Stress changes (ΔCFS) triggered by both coseismic rupture and aseismic slip resulting from this event. The co- and postseismic ΔCFS show similar patterns, but the magnitude of the postseismic ΔCFS is much lower (≤0.01 MPa). We found that ΔCFS notably increased on the Yushu segment of the Garze-Yushu-Xianshuihe Fault (GYXF), as well as the Maqin–Maqu and Tuosuo Lake sections of the East Kunlun Fault (EKF). Therefore, we infer that these fault segments may have a higher potential seismic risk and should be carefully monitored in the future.

Abstract Background Radical cystectomy and urinary diversion are the standard surgical treatments for patients with muscle-invasive or high-risk, or recurrent non-muscle-invasive bladder cancer. Although this approach significantly prolongs patient survival, it can lead to postoperative complications. This study aims to compare the efficacy and complications of bilateral cutaneous ureterostomy with a single subumbilical stoma to those of cutaneous ureterostomy with two stomas and an ileal conduit as a means of urinary diversion after radical cystectomy. The findings of this study will provide valuable information for healthcare providers in selecting the appropriate urinary diversion method for their patients. Methods The clinical data for 108 patients who received bilateral cutaneous ureterostomy with a single subumbilical stoma (ureterostomy with a single stoma group), cutaneous ureterostomy with two stomas (ureterostomy with two stomas group), or an ileal conduit (ileal conduit group) after radical cystectomy were retrospectively analysed. The operative time, pathological stage, survival status, perioperative complication rate, rate of successful first extubation, rehospitalization rate at 6 months after surgery,ostomy-related medical costs,and postoperative quality of life were compared between the three groups of patients. Results A significant difference in the operative time was found between the three groups (P = 0.001). No significant differences in pathological stage, survival status, perioperative complication rate, rehospitalization rate at 6 months after surgery, or bladder cancer index (BCI) score were identified among the three groups. The difference in the successful first extubation rate between the three groups of patients was significant (P = 0.001). Significant differences in ostomy-related medical costs were observed among the three groups of patients (P = 0.006). Conclusion A single subumbilical stoma for bilateral cutaneous ureterostomy after radical cystectomy may result in shorter surgery time, increased success rates for initial catheter removal, and lower medical expenses. However, to confirm these findings, further prospective randomized clinical trials are necessary.

Abstract Background Salivary carcinoma ex pleomorphic adenoma (CXPA) is defined as a carcinoma that develops from benign pleomorphic adenoma (PA). Abnormally activated Androgen signaling pathway and amplification of HER-2/neu(ERBB-2) gene are known to be involved in CXPA tumorigenesis. Recent progress in tumour microenvironment research has led to identification that extracellular matrix (ECM) remodelling and increased stiffness act as critical contributing role in tumour carcinogenesis. This study examined ECM modifications to elucidate the mechanism underlying CXPA tumorigenesis. Results PA and CXPA organoids were successfully established. Histological observation, immunohistochemistry (IHC), and whole-exome sequencing demonstrated that organoids recapitulated phenotypic and molecular characteristics of their parental tumours. RNA-sequencing and bioinformatic analysis of organoids showed that differentially expressed genes are highly enriched in ECM-associated terms, implying that ECM alternations may be involved in carcinogenesis. Microscopical examination for surgical samples revealed that excessive hyalinized tissues were deposited in tumour during CXPA tumorigenesis. Transmission electron microscopy confirmed that these hyalinized tissues were tumour ECM in nature. Subsequently, examination by picrosirius red staining, liquid chromatography with tandem mass spectrometry, and cross-linking analysis indicated that tumour ECM was predominantly composed of type I collagen fibers, with dense collagen alignment and an increased level of collagen cross-linking. IHC revealed the overexpression of COL1A1 protein and collagen-synthesis-related genes, DCN and IGFBP5 (p

Amine modification is an effective strategy to improve the H2S removal performance of Cu-BTC. In order to avoid the problem of pore blockage after amine modification in post synthesis impregnation, herein a series of Cu-BTC modified with organic amine adsorbents were prepared via an in-situ one-pot method and the H2S removal performance under ambient conditions was tested. It is found that the introduced organic amines, depending on the types of amine selected, have a significant influence on the growth of Cu-BTC and its textural properties. The H2S removal performance on the as-prepared materials suggested that the amine modified samples remarkably improved the H2S removal capacities with an order of BA-Cu-BTC > TEA-Cu-BTC > TEOA-Cu-BTC > Cu-BTC. Besides the enlarged surface area and the increased mesopores volumes, BA has the advantages of smaller steric hindrance and –NH2 groups, among which the former increased the accessibility of Cu active sites while the latter acted as additional active sites for H2S capturing, thus affording BA-Cu-BTC highest breakthrough capacity of 77.3 mg S/g. Overall, this study elaborates the effect of organic amines in-situ modification on the Cu-BTC structure and desulfurization.

Abstract Sepsis, whole‐body inflammation caused by the contamination of blood by bacteria and endotoxins, affects millions of patients annually with high mortality rates. A recent promising approach to treat sepsis involves the removal of bacteria and endotoxins using extracorporeal blood‐cleansing devices. However, poor specificity, slow recognition of pathogens, and high costs remain the main limitations. Here, the melanin, a biologically derived pigment, is reported for the rapid binding of bacteria and endotoxins from the contaminated blood . This novel approach utilizes the specific binding between Zn2+‐loaded melanin and bacteria/endotoxins with minimal nonspecific interactions with human blood components. Melanin contains various chemical functional groups that allow reversible chelation of metallic ions such as Zn2+ via redox reactions. Zn2+ enables rapid and specific binding with bacteria/endotoxins due to the strong electrostatic interactions between Zn2+ and phosphate ions. The presence of various zinc‐binding proteins on the bacterial cell membrane further enhances the binding. The well‐known biocompatibility and low cost make melanin an ideal material to interface with human blood. Zn2+‐charged melanin can remove 90% of E. coli and 100% of endotoxin in PBS and human blood. Zn2+‐melanin also demonstrated excellent hemocompatibility shown by protein adsorption, blood coagulation, and hemolysis tests.

To improve ocean thermal energy conversion (OTEC) system efficiency, four systems utilizing the waste heat recovery from offshore oil and gas platform are proposed, including flue gas boosting OTEC (system I), production water boosting surface seawater OTEC (system II), production water boosting working medium OTEC (system III), and production water boosting vapor OTEC (system IV). The system thermodynamic performance are investigated. The results show that system IV has larger power generation (Wnet), thermal efficiency (ηth) and exergy efficiency (ηex) than others. Compared with single OTEC system, for system IV, Wnet, ηth and ηex are increased by 1569.13 %, 70.35 % and 138.26 %, respectively. For system IV, with the increase of flue gas waste heat quantity from 2000 to 4000 kW, Wnet, ηth and ηex are increased by 562 %, 390 % and 181 % respectively; with the increase of production water waste heat quantity from 0 to 100 kW, Wnet, ηth and ηex are 12.59 %, 5.73 % and 2.86 % respectively. Wnet rises first and then decreases with the increase of evaporation pressure (Peva) or base fluid concentration (xb), presenting an optimal Peva of 1.5 MPa and xb of 0.82 corresponding to the maximum Wnet; Wnet decreases with the increase of condensation temperature.

Quantum interference (QI) has been widely studied in advanced materials and can be exploited to control the nonlinear response by varying the relative phase between the incident optical pulses. However, the contribution of the coherent injected photocurrent by QI from the indirect gap materials is still unclear because of the much weaker phonon-assisted absorption compared with that from the direct gap materials. Here, we investigate the coherent injected photocurrent in mono- and multilayer MoS2 with thickness at the nanometer scale under 2-color light excitation by detecting the generated coherent terahertz (THz) wave. We observe that the THz radiation can be controlled by the relative phase. Besides, we obtain similar experimental results of the THz wave generation from mono- and multilayer MoS2 when we change the relative polarization angle between 𝜔 and 2𝜔 pulses, in comparison to the case of direct gap materials. Thus, these experimental results further verify that, in multilayer MoS2 with an indirect gap, QI in the direct gap region is the dominant process for the THz wave generation. Furthermore, we demonstrate that QI can be a more effective mechanism to induce THz radiation than optical rectification under single-color light excitation. This study enhances the understanding of QI in indirect gap materials and highlights the potential of 2-color light excitation for investigating third-order nonlinear processes in advanced materials.

Abstract Background Human papillomavirus (HPV) integration into the host genome is an important factor in HPV(+)OPSCC carcinogenesis, in conjunction with HPV oncoproteins E6/E7. However, a well‐studied investigation about virus–host interaction still needs to be completed. Our objective is to characterise HPV integration to investigate potential mechanisms of tumourigenesis independent of E6/E7 oncoproteins. Materials and methods High‐throughput viral integration detection was performed on 109 HPV(+)OPSCC tumours with relevant clinicopathological information. Of these tumours, 38 tumours underwent targeted gene sequencing, 29 underwent whole exome sequencing and 26 underwent RNA sequencing. Results HPV integration was detected in 94% of tumours (with a mean integration count of 337). Tumours occurring at the tonsil/oropharyngeal wall that exhibit higher PD‐L1 expression demonstrated increased integration sites (p = .024). HPV exhibited a propensity for integration at genomic sites located within specific fragile sites (FRA19A) or genes associated with functional roles such as cell proliferation and differentiation (PTEN, AR), immune evasion (CD274) and glycoprotein biosynthesis process (FUT8). The viral oncogenes E2, E4, E6 and E7 tended to remain intact. HPV fragments displayed enrichment within host copy number variation (CNV) regions. However, insertions into genes related to altered homologous recombination repair were infrequent. Genes with integration had distinct expression levels. Fifty‐nine genes whose expression level was affected by viral integration were identified, for example, EPHB1, which was reported to be involved in cellular protein metabolic process. Conclusions HPV can promote oncogenesis through recurrent integration into functional host genome regions, leading to subsequent genomic aberrations and gene expression disruption. This study characterises viral integrations and virus–host interactions, enhancing our understanding of HPV‐related carcinogenesis mechanisms.

With the rapid development of the digital economy, there has been an explosion in the amount of data generated. Data have become a vital resource for nations, just as tangible assets and human capital are crucial factors of production. Consequently, protecting digital security has become paramount. However, the increasing frequency of various data security incidents in recent years has exposed issues such as inadequate platform governance, lack of government regulation, and incomplete digital security governance (DSG) mechanisms. This study aims to create a healthy and open digital ecosystem and proposes a new digital security governance framework. It subdivides traditional government departments into local governments and the central government. Together with third-party platforms, they are analyzed as participants in an evolutionary game. The study examines the evolutionary stability of strategy choices made by each party and explores the relationship between key factors such as negative externalities, data security incident probabilities, and their impacts on strategy selection using numerical simulations. The research findings indicate the following. (1) Key parameters such as implicit benefits, government subsidies, and negative externalities play a significantly positive role in the development of the digital ecosystem. (2) The central government consistently tends towards emergency response, considering the overall societal perspective, as long as it is capable of bearing the costs. (3) Local governments may exhibit free-riding behavior during the governance process. To address this, it is important to increase the willingness of third-party platforms to govern and oversee the participation of local governments, which is an effective way to prevent data crises. The study also identifies different governance models in various environments: (1) a digital security governance model in a stable market environment, involving increased central government intervention and supervision of local governments’ participation; and (2) a digital security governance model in the event of a data crisis, where the central government establishes subsidies that exceed the governance costs of local governments to enhance the willingness of third-party platforms to govern. Finally, recommendations and strategies are presented to enhance the level of digital security governance.

AIM: To explore the characteristics of astigmatism in preschool children before, during and after the COVID-19 epidemic, so as to provide a reference for further prevention and control of children's vision.METHODS: In the consecutive four years from January 2018 to December 2021, a retrospective analysis of vision data was conducted on 2 273 preschool children(4 546 eyes)younger than 4 years old who participated in children's vision screening test in Baiyun district, Guangzhou. They were divided into 1-year old group(ages

Abstract Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti‐hypertensive. Using a meta‐analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002–2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (ΔSBP) was –1.42 (95% CI: –2.38, –0.46; p = .004) and diastolic blood pressure (ΔDBP) was 0.82 (95% CI: –1.28, –0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non‐significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi‐ethnic, large sample pool size, and a long period follow‐up study is still required to assert these claims.

Abstract Precancerous lesions of the oral mucosa, especially those accompanied by moderate to severe dysplasia, contribute to the initiation of oral squamous cell carcinoma (OSCC). However, the cellular compositions and spatial organization of the precancerous stage and how these factors promote human OSCC initiation remain unclear. Here, we built a single-cell transcriptome atlas and a spatial transcriptome map after obtaining data from pairwise human oral mucosal biopsies of 9 individuals consisting of very early-stage OSCC, adjacent precancerous lesions with moderate to severe dysplasia, as well as a matched normal region. An altered epithelial gene-expression profile was identified which favored OSCC initiation. This observation was coupled with distinct fibroblast, monocytic, and regulatory T-cell subclusters involved in reshaping the microenvironment. In particular, a unique immune-inhibitory monocyte subtype and spatial-switching regulation of VEGF signaling were observed surrounding precancerous lesions, concertedly strengthening activities in promoting cancer initiation. Collectively, our work elucidated the cellular landscapes and roles of precancerous lesions underlying OSCC initiation, which is essential for understanding the entire OSCC initiation process and helps inform therapeutic strategies for cancer intervention.

The properties of small size, low noise, high performance and no wear-out have made the hemispherical resonator gyroscope a good choice for high-value space missions. To enhance the precision of the hemispherical resonator gyroscope for use in tasks with large angular velocities and angular accelerations, this paper investigates the standing wave precession of a non-ideal hemispherical resonator under nonlinear high-intensity dynamic conditions. Based on the thin shell theory of elasticity, a dynamic model of a hemispherical resonator is established by using Lagrange’s second kind equation. Then, the dynamic model is equivalently transformed into a simple harmonic vibration model of a point mass in two-dimensional space, which is analyzed using a method of averaging that separates the slow variables from the fast variables. The results reveal that taking the nonlinear terms about the square of the angular velocity and the angular acceleration in the dynamic equation into account can weaken the influence of the 4th harmonic component of a mass defect on standing wave drift, and the extent of this weakening effect varies with the dimensions of the mass defects, which is very important for steering the development of the high-precision hemispherical resonator gyroscope.

The southeastern Tibetan Plateau (SETP), which hosts the most extensive marine glaciers on the Tibetan Plateau (TP), exhibits enhanced sensitivity to climatic fluctuations. Under global warming, persistent glacier mass depletion within the SETP poses a risk to water resource security and sustainability in adjacent nations and regions. This study deployed a high-precision ICESat-2 satellite altimetry technique to evaluate SETP glacier thickness changes from 2018 to 2022. Our results show that the average change rate in glacier thickness in the SETP is −0.91 ± 0.18 m/yr, and the corresponding glacier mass change is −7.61 ± 1.52 Gt/yr. In the SETP, the glacier mass loss obtained via ICESat-2 data is larger than the mass change in total land water storage observed by the Gravity Recovery and Climate Experiment follow-on satellite (GRACE-FO), −5.13 ± 2.55 Gt/yr, which underscores the changes occurring in other land water components, including snow (−0.44 ± 0.09 Gt/yr), lakes (−0.06 ± 0.02 Gt/yr), soil moisture (1.88 ± 1.83 Gt/yr), and groundwater (1.45 ± 0.70 Gt/yr), with a closure error of −0.35 Gt/yr. This demonstrates that this dramatic glacier mass loss is the main reason for the decrease in total land water storage in the SETP. Generally, there are decreasing trends in solid water storage (glacier and snow) against stable or increasing trends in liquid water storage (lakes, soil moisture, and groundwater) in the SETP. This persistent decrease in solid water is linked to the enhanced melting induced by rising temperatures. Given the decreasing trend in summer precipitation, the surge in liquid water in the SETP should be principally ascribed to the increased melting of solid water.

Downhole turbine generators (DHTG) installed within drill-string are susceptible to internal and external excitation during the drilling process, causing significant dynamic loads on bearings, and thereby reducing the bearing’s service life. In this study, a finite element model of an unbalanced rotor-bearing system (RBS) of DHTG with multi-frequency excitations, based on the Lagrangian motion differential equation, is established. The responses of the RBS under different drill-string excitations in terms of time-domain response, whirl orbit, and spectrum are analyzed. For a constant rotor speed, lateral harmonic translational and lateral oscillation both transform the whirl orbit to quasi-periodic, while axial rotation only changes the response amplitude. Changing the duration of pulse excitation leads to different response forms. Then, the dynamic characteristics of the RBS supported by a squeeze film damper (SFD) are investigated. The results indicate that SFD effectively reduces the displacement response amplitude and bearing force near the critical speed. As the axial rotation angular velocity of the drill-string increases, the first critical speed and displacement response decrease, while the variation of lateral oscillation frequency and amplitude has limited impact on them. The established model provides a means for analyzing the dynamic characteristics of DHTG’s RBS under drill-string excitations during the design stage.

BackgroundOccludin (OCLN) is an important tight junction protein and has been reported to be abnormally expressed in the development of malignant tumors. However, its biomarker and carcinogenic roles in kidney renal clear cell carcinoma (KIRC) are less investigated.MethodsThe Cancer Genome Atlas database and Human Protein Atlas database were used to analyze the expression of OCLN in KIRC. UALCAN database and methylation-specific PCR assay were used to evaluate the methylation level of OCLN in KIRC. Univariate and multivariate Cox regression analyses were performed to model the prognostic significance of OCLN in KIRC patient cohorts. The correlation between OCLN expression and the immune cell infiltration, immune-related function and immune checkpoints were explored. Finally, EdU, scratch assay and transwell experiments were conducted to validate the role of OCLN in KIRC development.ResultsThe expression of OCLN was significantly downregulated in KIRC, compared with normal renal tissues (p

Two-dimensional phase unwrapping (2-D PU) is the process of converting the measured phase into the real phase in interferometric signal processing. Reliable unwrapping results are critical for digital elevation model generation using interferometric synthetic aperture radar (InSAR) and interferometric synthetic aperture sonar (InSAS). The majority of previous research has concentrated on accuracy, whereas the computational efficiency must be taken into account for the interferometric measurement system that requires real-time processing. This article proposes a low-time-consuming algorithm that can accomplish high-precision 2-D PU for this application scenario. The neural network and a new path-based 2-D PU algorithm make up this algorithm. First, the incorrect region in the gradient field is predicted and corrected using the neural network. The output channelwise variance is then calculated and used to generate the quality maps. Finally, to achieve phase reconstruction, the path-based algorithm performs path planning and flooding integral according to quality maps and compensated gradient. This article also provides a recommended data structure implementation to ensure the algorithm's high efficiency. Experimental results using InSAR and InSAS data show that the proposed algorithm is highly efficient and accurate.

Abstract. Background. The National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic lymph node dissection (PLND) in NCCN high- and intermediate-risk prostate cancer patients. We tested for PLND nonadherence (no-PLND) rates within the Surveillance Epidemiology and End Results (2010–2015). Materials and methods. We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria (n = 23,495). Nonadherence rates to PLND were tabulated and further stratified according to NCCN risk subgroups, race/ethnicity, geographic distribution, and year of diagnosis. Results. Overall, the no-PLND rate was 26%; it was 41%, 25%, and 11% in the NCCN intermediate favorable, intermediate unfavorable, and high-risk prostate cancer patients, respectively (p < 0.001). Over time, the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup. Georgia exhibited the highest no-PLND rate (49%), whereas New Jersey exhibited the lowest (15%). Finally, no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup, where Asians exhibited the lowest no-PLND rate (20%) versus African Americans (27%) versus Whites (26%) versus Hispanic-Latinos (25%). Conclusions. The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order. Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination. In all the NCCN risk subgroups, the no-PLND rates decreased over time.

Abstract Actively controlling the polarization states of terahertz (THz) waves is essential for polarization-sensitive spectroscopy, which has various applications in anisotropy imaging, noncontact Hall measurement, and vibrational circular dichroism. In the THz regime, the lack of a polarization modulator hinders the development of this spectroscopy. We theoretically and experimentally demonstrate that conjugated bilayer chiral metamaterials (CMMs) integrated with Ge2Sb2Te5 (GST225) active components can achieve nonvolatile and continuously tunable optical activity in the THz region. A THz time-domain spectroscopic system was used to characterize the device, showing a tunable ellipticity (from ‒36° to 0°) and rotation of the plane polarization (from 32° to 0°) at approximately 0.73 THz by varying the GST225 state from amorphous (AM) to crystalline (CR). Moreover, a continuously tunable chiroptical response was experimentally observed by partially crystallizing the GST225, which can create intermediate states, having regions of both AM and CR states. Note that the GST225 has an advantage of nonvolatility over the other active elements and does not require any energy to retain its structural state. Our work allows the development of THz metadevices capable of actively manipulating the polarization of THz waves and may find applications for dynamically tunable THz circular polarizers and polarization modulators for THz emissions.