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Recurrent event analyses have found a wide range of applications in biomedicine, public health, and engineering, among others, where study subjects may experience a sequence of event of interest during follow-up. The R package reReg offers a comprehensive collection of practical and easy-to-use tools for regression analysis of recurrent events, possibly with the presence of an informative terminal event. The regression framework is a general scale-change model which encompasses the popular Cox-type model, the accelerated rate model, and the accelerated mean model as special cases. Informative censoring is accommodated through a subject-specific frailty without any need for parametric specification. Different regression models are allowed for the recurrent event process and the terminal event. Also included are visualization and simulation tools.

Abstract RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid–protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure–activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy. Graphical Abstract

Abstract Background The triglyceride-glucose (TyG) index is considered a dependable biomarker for gauging insulin resistance. The atherogenic index of plasma (AIP) represents a marker reflecting atherosclerosis. However, there is currently no study specifically exploring the associations of these two biomarkers with the severity of new-onset coronary artery disease (CAD) under different glucose metabolic states. Therefore, this study aims to evaluate the correlations of these two biomarkers with CAD severity in patients newly diagnosed with CAD under various glucose metabolism conditions. Method Totally 570 subjects first administered coronary angiography were enrolled, including 431 first diagnosed CAD patients and 139 non-CAD patients. CAD severity was gauged by the quantity of narrowed arteries (single-vessel and multi-vessel CAD). According to WHO diabetes guidelines, glucose metabolic states were divided into normal glucose regulation (NGR), pre-diabetes mellitus (Pre-DM), and diabetes mellitus (DM). The relationships of the TyG index and AIP with CAD severity were validated by logistic regression analysis, including adjustment for traditional cardiovascular risk elements and medical treatments. Their predictive efficacy for CAD was evaluated by receiver operating characteristic (ROC) curves. Result The TyG index and AIP were independently correlated with CAD in accordance with logistic regression analysis (both P

Highlights A strategy based on metal-organic decomposition is proposed to enhance the tube-tube interactions of carbon nanotubes (CNTs). The robust tube-tube interactions of CNTs enhance both EMI shielding performance and mechanical properties of CNT film. This innovative approach provides an effective way to obtain high-performance CNT film.

In response to the challenge of mitigating flight delays, this study introduces an innovative solution that encompasses the prediction of delay durations for existing flights and the subsequent optimization of ground service processes based on these predictions. The indirect forecasting of flight delays is achieved through the construction of a random forest model, exhibiting a remarkable 100% accuracy when considering a 15-minute standard for flight delays. In light of the delay prediction outcomes, distinct delay coefficients are assigned to individual flights, facilitating the development of a ground service optimization model through the application of a genetic algorithm. Within the genetic algorithm optimization framework, significant enhancements have been implemented in the gene encoding of the initial population, incorporating a segmented encoding approach. Employing this refined model to optimize the service sequence and duration of ground service vehicles for all flights culminates in the notable accomplishment of achieving zero delays for the entire set of flights.

Abstract Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients.

Magnetron sputtering systems are widely used for depositing industrially important coatings. Research has been conducted to optimize and improve these structures to increase coating effectiveness and target utilization. The paper investigates the engineering problem of uneven target etching caused by an uneven magnetic field in magnetron sputtering equipment. The characteristics of the desired magnetic field distribution required by magnetron sputtering equipment are analyzed, and a corresponding excitation structure and analytical model for cylindrical magnetron sputtering equipment are proposed and calculated. The uniform magnetic field design is realized by analytical modeling of the excitation structure. The axial magnetic field distributions produced by an axisymmetric solenoid system and several similar excitation structures are analyzed and compared. The analytical results were verified through finite element simulations and experiments, demonstrating the accuracy and effectiveness of the method. The excitation structure, which is designed with a uniform magnetic field, can produce an axial component of magnetic flux density with a uniformity deviation of less than 4.3% across 73% of the target surface. The analytical model describes the distribution of the axial component of the magnetic flux density and optimizes the magnetic field. The model enables the simulation of plasma distribution and film growth, aiming to enhance the target utilization rate and substrate deposition rate. The conclusions serve as a reference for designing high-performance magnetron sputtering equipment.

Abstract Background One-stage jaw reconstruction with fibular flap and prosthetic rehabilitation restores bony and dental continuity simultaneously. It was also called as “jaw-in-a-day (JIAD)” technique. However, bone volume and height of fibular flap may be insufficient for dental implant insertion. The provision of a considerable amount of bone makes an iliac flap the ideal choice in these cases. We present the first case report to document the use of one-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap. Case presentation We modified the conventional JIAD workflow to make it suitable for iliac flap. Two cases were presented who both underwent segmental mandibulectomy for ameloblastoma. Virtual surgical planning was performed in all cases. The iliac crest was positioned upward to provide cortical bone for achieving primary stability of dental implants. Similar to the “all-on-4” procedure, the iliac bone was placed 12 to 15 mm below the occlusal plane to create adequate space for the implant-retained prosthesis. Immediate implant-based dental rehabilitation was performed at same stage. The surgery was successful in all cases without any short-term complications. In the first postoperative week, patients were given a liquid diet through a nasal feeding tube. The liquid diet is advised until 1 month after the surgery. Thereafter, a soft diet is recommended. Patients were advised to resume routine mastication and normal diet 3 months after the surgery. Peri-implantitis occurred in one patient, and additional gingival graft was required. Postoperative function and esthetics were satisfactory at the last follow-up visit. Conclusions One-stage jaw reconstruction and prosthetic rehabilitation with the iliac flap are safe and useful for restoring postoperative function and esthetics. It should be used in more cases with a longer follow-up in further studies.

Objective To investigate the occurrence of flight illusions and explore its influencing factors and countermeasures in army aviators in cold regions. Methods Comprehensive Flight Illusion Scale was applied to investigate flight illusions, related influencing factors and countermeasures among 74 army aviators in cold regions from December 2022 to February 2023. SPSS 22.0 statistics was used for statistical analysis to compare the differences among variables and identify the influencing factors of flight illusions. Results For the 74 issued questionnaires, all of them were retrieved validly, with a rate of 100%. The incidence rate of flight illusions was 32.43%. There was a statistical difference between flight time and the occurrence of flight illusions (P < 0.05). There were 3 types of flight illusions with higher incidences in cold regions, that is distance illusion (20.27%), tilt illusion (18.92%) and relative position illusion (16.22%). The 3 flight illusions with relatively lower incidences were detachment phenomenon (4.05%), rotational illusion (4.05%), and inverted flight illusion (2.70%). After occurrence of illusions, 66.67% of the aviators experienced symptoms such as tension, "hard-to-move lever" headache, dizziness and post-flight insomnia. Almost all of the aviators were of fully awareness and acceptance of the active approaches to dealing with flight illusions, but still 50% of them believed that passive waiting intervention measures could be used. The results of statistical analysis on related influencing factors indicated that statistical differences were observed in all the listed items except flight subject with the occurrence of flight illusions (P < 0.05). Conclusion During short period flight in cold regions in winter, army aviators experience obvious psychological and physiological reactions after occurrence of flight illusions, and their anxiety and fatigue state, external climate and landform environment, and cabin interface and flight parameters are all related to the occurrence.

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

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model’s discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894–0.934) and 0.923 (95% CI, 0.895–0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model’s favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

ABSTRACTJaceosidin (JAC) is a natural flavonoid with anti-oxidant and other pharmacological activities; however, its anti-cancer mechanism remains unclear. We investigated the mechanism of action of JAC in gastric cancer cells. Cytotoxicity and apoptosis assays showed that JAC effectively killed multiple gastric cancer cells and induced apoptosis in human gastric adenocarcinoma AGS cells via the mitochondrial pathway. Network pharmacological analysis suggested that its activity was linked to reactive oxygen species (ROS), AKT, and MAPK signaling pathways. Furthermore, JAC accumulated ROS to up-regulate p-JNK, p-p38, and IκB-α protein expressions and down-regulate the p-ERK, p-STAT3, and NF-κB protein expressions. Cell cycle assay results showed that JAC accumulated ROS to up-regulate p21 and p27 protein expressions and down-regulate p-AKT, CDK2, CDK4, CDK6, Cyclin D1, and Cyclin E protein expressions to induce G0/G1 phase arrest. Cell migration assay results showed JAC accumulated ROS to down-regulate Wnt-3a, p-GSK-3β, N-cadherin, and β-catenin protein expressions and up-regulate E-cadherin protein expression to inhibit migration. Furthermore, N-acetyl cysteine pre-treatment prevented the change of these protein expressions. In summary, JAC induced apoptosis and G0/G1 phase arrest and inhibited migration through ROS-mediated signaling pathways in AGS cells.

Study region: Two typical mountainous Haihe River Basins: The Xiaojue Basin and the Yehe River Basin Study focuses: The mountainous Haihe River Basin has suffered from a water crisis duo to large-scale restoration. Quantifying the hydrological impacts of vegetation restoration is necessary for local water management. In this study, we used the Soil and Water Assessment Tool (SWAT) hydrological model, in combination with two vegetation restoration scenarios, to analyze the effects of vegetation restoration on runoff and its runoff components (surface runoff, baseflow, and total runoff) New hydrological insights for the region: Our results indicated a general decrease in surface runoff and an increase in baseflow as a result of vegetation restoration. At the seasonal timescale, total runoff and surface runoff decreases mainly concentrated in the flood season, and slightly increased in the non-flood season, and baseflow showed the opposite trend during the flood-season in the Xiaojue and Yehe River Basin. The magnitude of change in runoff components in the Yehe River Basin was higher than that in the Xiaojue Basin, and the Yehe River Basin has a larger water yield capability. This study advances our knowledge on the way in which vegetation affects runoff and offers recommendations for water resources management

Cellular movement is essential for many vital biological functions where it plays a pivotal role both at the single cell level, such as during division or differentiation, and at the macroscopic level within tissues, where coordinated migration is crucial for proper morphogenesis. It also has an impact on various pathological processes, one for all, cancer spreading. Cell migration is a complex phenomenon and diverse experimental methods have been developed aimed at dissecting and analysing its distinct facets independently. In parallel, corresponding analytical procedures and tools have been devised to gain deep insight and interpret experimental results. Here we review established experimental techniques designed to investigate specific aspects of cell migration and present a broad collection of historical as well as cutting-edge computational tools used in quantitative analysis of cell motion.

Abstract Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross‐linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over‐accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS‐responsive and Vitamin A (VA) decorated micelles (named LR‐SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR‐SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS‐responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross‐linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR‐SSVA is a safe and efficient ROS‐response and PSC‐targeted drug‐delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.

Biomechanical factors are strongly linked with the emergence and development of intervertebral disc degeneration (IVDD). The intervertebral disc (IVD), as a unique enclosed biomechanical structure, exhibits distinct mechanical properties within its substructures. Damage to the mechanical performance of any substructure can disrupt the overall mechanical function of the IVD. Endplate degeneration serves as a significant precursor to IVDD. The endplate (EP) structure, especially the cartilaginous endplate (CEP), serves as a conduit for nutrient and metabolite transport in the IVD. It is inevitably influenced by its nutritional environment, mechanical loading, cytokines and extracellular components. Currently, reports on strategies targeting the CEP for the prevention and treatment of IVDD are scarce. This is due to two primary reasons: first, limited knowledge of the biomechanical microenvironment surrounding the degenerated CEP cells; and second, innovative biological treatment strategies, such as implanting active cells (disc or mesenchymal stem cells) or modulating natural cell activity through the addition of therapeutic factors or genes to treat IVDD often overlook a critical aspect-the restoration of the nutrient supply function and mechanical microenvironment of the endplate. Therefore, restoring the healthy structure of the CEP and maintaining a stable mechanical microenvironment within the EP are crucial for the prevention of IVDD and the repair of degenerated IVDs. We present a comprehensive literature review on the mechanical microenvironment characteristics of cartilage endplates and their associated mechanical signaling pathways. Our aim is to provide valuable insights into the development and implementation of strategies to prevent IVDD by delaying or reversing CEP degeneration.