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Abstract Objectives Synchronous colorectal cancer peritoneal metastasis (CRPM) has a poor prognosis. This study aimed to create a radiomics-boosted deep learning model by PET/CT image for risk assessment of synchronous CRPM. Methods A total of 220 colorectal cancer (CRC) cases were enrolled in this study. We mapped the feature maps (Radiomic feature maps (RFMs)) of radiomic features across CT and PET image patches by a 2D sliding kernel. Based on ResNet50, a radiomics-boosted deep learning model was trained using PET/CT image patches and RFMs. Besides that, we explored whether the peritumoral region contributes to the assessment of CRPM. In this study, the performance of each model was evaluated by the area under the curves (AUC). Results The AUCs of the radiomics-boosted deep learning model in the training, internal, external, and all validation datasets were 0.926 (95% confidence interval (CI): 0.874–0.978), 0.897 (95% CI: 0.801–0.994), 0.885 (95% CI: 0.795–0.975), and 0.889 (95% CI: 0.823–0.954), respectively. This model exhibited consistency in the calibration curve, the Delong test and IDI identified it as the most predictive model. Conclusions The radiomics-boosted deep learning model showed superior estimated performance in preoperative prediction of synchronous CRPM from pre-treatment PET/CT, offering potential assistance in the development of more personalized treatment methods and follow-up plans. Critical relevance statement The onset of synchronous colorectal CRPM is insidious, and using a radiomics-boosted deep learning model to assess the risk of CRPM before treatment can help make personalized clinical treatment decisions or choose more sensitive follow-up plans. Key Points Prognosis for patients with CRPM is bleak, and early detection poses challenges. The synergy between radiomics and deep learning proves advantageous in evaluating CRPM. The radiomics-boosted deep-learning model proves valuable in tailoring treatment approaches for CRC patients. Graphical Abstract

Abstract Vortices in superconductors can help identify emergent phenomena but certain fundamental aspects of vortices, such as their entropy, remain poorly understood. Here, we study the vortex entropy in underdoped Bi2Sr2CaCu2O8+x by measuring both magneto-resistivity and Nernst effect on ultrathin flakes (≤2 unit-cell). We extract the London penetration depth from the magneto-transport measurements on samples with different doping levels. It reveals that the superfluid phase stiffness ρ s scales linearly with the superconducting transition temperature T c , down to the extremely underdoped case. On the same batch of ultrathin flakes, we measure the Nernst effect via on-chip thermometry. Together, we obtain the vortex entropy and find that it decays exponentially with T c or ρ s . We further analyze the Nernst signal above T c in the framework of Gaussian superconducting fluctuations. The combination of electrical and thermoelectric measurements in the two-dimensional limit provides fresh insight into high temperature superconductivity.

Along with the explosive utilization of intelligent and bionic robotics, the rise of somatosensory system with excellent flexibility and multiple biological sensing characteristic emerges as a substantial crux of this domain. Herein, we propose a flexible high-performance multi-mode sensor for real-time proximity–pressure–temperature perception based on a monolithic sensing unit with fingerprint-like hierarchical architecture. The monolithic sensing unit, primarily constituted by a double-permeable ionic liquids/Multi-walled nanotubes conductive network, demonstrates dual-functionality in detecting pressure and temperature. Making use of the further synergy of rational topographical architecture engineering and feasible decoupling algorithm construction, extraordinary progress in sensing performances for both pressure and temperature are attained with negligible mutual interferences. Additionally, the sensor is capable of switching to touchless mode to detect objects at distance up to 200 mm, validating its remarkable proximity sensing ability. The multifunctional nature of sensor is further substantiated through its integration with a robotic hand, highlighting its practical applicability in advanced robotic systems.

Abstract Hydrogel sensors are widely utilized in soft robotics and tissue engineering due to their excellent mechanical properties and biocompatibility. However, in high‐water environments, traditional hydrogels can experience significant swelling, leading to decreased mechanical and electrical performance, potentially losing shape, and sensing capabilities. This study addresses these challenges by leveraging the Hofmeister effect, coupled with directional freezing and salting‐out techniques, to develop a layered, high‐strength, tough, and antiswelling PVA/MXene hydrogel. In particular, the salting‐out process enhances the self‐entanglement of PVA, resulting in an S‐PM hydrogel with a tensile strength of up to 2.87 MPa. Furthermore, the S‐PM hydrogel retains its structure and strength after 7 d of swelling, with only a 6% change in resistance. Importantly, its sensing performance is improved postswelling, a capability rarely achievable in traditional hydrogels. Moreover, the S‐PM hydrogel demonstrates faster response times and more stable resistance change rates in underwater tests, making it crucial for long‐term continuous monitoring in challenging aquatic environments, ensuring sustained operation and monitoring.

Abstract Actuators based on shape memory polymers and composites incorporating nanomaterial additives have been extensively studied; achieving both high output stress and precise shape change by low‐cost, scalable methods is a long‐term‐desired yet challenging task. Here, conventional polymers (polyurea) and carbon nanotube (CNT) fillers are combined to fabricate reinforced composite fibers with exceptional actuation performance, by a wet‐spinning method amenable for continuous production. It is found that a thermal‐induced shrinkage step could obtain densified strong fibers, and the presence of CNTs effectively promotes the tensile orientation of polymer molecular chains, leading to much improved mechanical properties. Consequently, the CNT/ polyurea composite fibers exhibit stresses as high as 33 MPa within 0.36 s during thermal actuation, and stresses up to 22 MPa upon electrical stimulation enabled by the built‐in conductive CNT networks. Utilizing the flexible thin fibers, various shape change behavior are also demonstrated including the conversion between different structures/curvatures, and recovery of predefined simple patterns. This high‐performance composite fibers, capable of both thermal and electrical actuation and produced by low‐cost materials and fabrication process, may find many potential applications in wearable devices, robotics, and biomedical areas.

Background: The gut microbiota (GM) plays an important role in the development of immune-related diseases, and the immune response is one of the pathomechanisms of depression (Dep); whether the effect of GM on Dep is mediated by immune cells (ImC) is unclear. Objective: ImC may mediate the effect of GM on Dep. Our aim is to identify and quantify the role of immune characteristics as potential mediators. Methods: Pooled statistics for GM (n = 7738) and ImC (n = 3757) were obtained from publicly available genome-wide association studies (GWAS), and for Dep (n = 47,696) from the Finnish database R10. We used a mediated Mendelian randomization (MR) study to investigate the causal relationship between GM and Dep and the mediating role of ImC between GM and Dep associations. Results: The results showed that the genetically predicted GM was significantly correlated with both ImC as well as Dep. MR analysis identified five microbiomes that had significant causal effects on Dep (Methionine biosynthesis III, PWY-6737-Starch degradation V, Parasutterella excrementihominis, Parasutterella, and Lysine biosynthesis I). In addition, five of the 26 ImC trait significantly associated with GM were most closely associated with Dep (T cell %lymphocyte、CD28-CD127-CD25++CD8br AC、CD28-CD8br AC、CD27 receptor on peripheral blood plasma cells (CD27 on PB/PC) and CD11b receptor on mononuclear myeloid-derived suppressor cells (CD11b on Mo MDSC)). This mediated MR illustrates the causal role of methionine biosynthesis III on Dep (IVW: OR = 1.08, 95%CI [1.04,1.14], P = 0.001). And there was no strong evidence for a causal effect of depression on methionine biosynthesis III. In the B cell group, the proportion of CD27 on PB/PC mediated was 7.88 %(95%CI [−0.04,0.03]) of the total effect. This study further suggests that Dep patients should actively seek immunologic intervention therapy. Conclusion: This MR study found that GM may play a causal role in Dep by mediating ImC. Our findings will help to understand the pathogenic mechanism of GM in Dep and the risk of immune mediation.

Background: Globally, Parkinson's disease (PD) is one of the common neurodegenerative diseases in the elderly with increasing morbidity and disability, and its clinical pathogenesis is not clear. Objective: To compare the differences in disease severity and blood biomarkers levels and their correlation between patients with early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD). Methods: A total of 342 patients diagnosed with PD were retrospectively collected. PD patients were categorized into EOPD (24 patients) and LOPD (318 patients) according to the age of onset of the disease. The Hoehn-Yahr (HY) staging was used to assess the severity of the disease in PD patients. Subjective rating scales such as the Mini-mental State Examination (MMSE) were used to assess the motor and non-motor functions of the patients. The differences of objective blood biomarkers such as triglyceride (TG) between the two groups were investigated. The correlation between them and PD was explored by logistic analysis. Results: Percentage of EOPD group with HY staged as intermediate to late and Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Movement Disorder Society-Unified Parkinson's disease Rating Scale-III (MDS-UPDRS-III), Montreal Cognitive Assessment (MoCA) score and TG, non-high-density lipoprotein-cholesterol (N-HDL-C), homocysteine (HCY), apolipoprotein B (Apo-B), free triiodothyronine (FT3), free thyroxine (FT4), high-sensitivity C-reactive protein (hs-CRP) levels were lower than those in the LOPD group (P

With the development of synchrotron radiation sources and high-frame-rate detectors, the amount of experimental data collected at synchrotron radiation beamlines has increased exponentially. As a result, data processing for synchrotron radiation experiments has entered the era of big data. It is becoming increasingly important for beamlines to have the capability to process large-scale data in parallel to keep up with the rapid growth of data. Currently, there is no set of data processing solutions based on the big data technology framework for beamlines. Apache Hadoop is a widely used distributed system architecture for solving the problem of massive data storage and computation. This paper presents a set of distributed data processing schemes for beamlines with experimental data using Hadoop. The Hadoop Distributed File System is utilized as the distributed file storage system, and Hadoop YARN serves as the resource scheduler for the distributed computing cluster. A distributed data processing pipeline that can carry out massively parallel computation is designed and developed using Hadoop Spark. The entire data processing platform adopts a distributed microservice architecture, which makes the system easy to expand, reduces module coupling and improves reliability.

Abstract One-unit-cell FeSe films on SrTiO3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( $${\Delta }_{1}$$ Δ 1 ~15 meV vs. $${\Delta }_{2}$$ Δ 2 ~10 meV) and pairing temperatures (T p1~52.0 K vs. T p2~37.3 K), and correspondingly two-step nonlinear $$V \sim {I}^{\alpha }$$ V ~ I α behavior but a concurrent Berezinskii–Kosterlitz–Thouless (BKT)-like transition occurring at $${T}_{{{{{{\rm{BKT}}}}}}}$$ T BKT ~28.7 K. Moreover, the onset transition temperature $${T}_{{{{{{\rm{c}}}}}}}^{{{{{{\rm{onset}}}}}}}$$ T c onset ~54 K and zero-resistivity temperature $${T}_{{{{{{\rm{c}}}}}}}^{{{{{{\rm{zero}}}}}}}$$ T c zero ~31 K are consistent with T p1 and $${T}_{{{{{{\rm{BKT}}}}}}}$$ T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity.

Abstract Background Tinnitus is very common in patients with vestibular schwannoma (VS). We analyzed the related factors of tinnitus after surgery. Methods One hundred seventy-three patients diagnosed with unilateral VS operated via the retrosigmoid approach were included in the study. All patients underwent relevant examinations and completed the THI scale before surgery and 6 months after surgery. The prognosis of tinnitus was evaluated according to the changes in THI. Results Of the 129 preoperative tinnitus patients, postoperative tinnitus resolved in 12.4%, improved in 29.5%, remained unchanged in 28.6%, and worsened in 29.5%. 18.2% of 44 patients without preoperative tinnitus appeared new-onset tinnitus postoperatively. Thirty-six patients never had tinnitus. Patients with smaller tumor sizes (≤ 3 cm) were more likely to experience preoperative tinnitus. Younger patients and those with serviceable hearing preoperatively were more likely to report their tinnitus unchanged or worsened. A new onset of postoperative tinnitus in the preoperative non-tinnitus group was found in better preoperative hearing function. Conclusions In this study, 70% of patients had persistent tinnitus after vestibular schwannoma resection. The prognosis of tinnitus was influenced by age and preoperative hearing function. Tinnitus is a bothersome symptom and is often underestimated by doctors. Assessment of tinnitus is mandatory during the management of vestibular schwannoma.

Abstract Thermo‐electrochemical cells (TECs) provide a new potential for self‐powered devices by converting heat energy into electricity. However, challenges still remain in the fabrication of flexible and tough gel electrolytes and their compatibility with redox actives; otherwise, contact problems exist between electrolytes and electrodes during stretching or twisting. Here, a novel robust and neutral hydrogel with outstanding stretchability was developed via double‐network of crosslinked carboxymethyl chitosan and polyacrylamide, which accommodated both n‐type (Fe2+/Fe3+) and p‐type ([Fe(CN)6]3−/[Fe(CN)6]4−) redox couples and maintained stretchability (>300%) and recoverability (95% compression). Moreover, poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) textile electrodes with porous structure are integrated into gel electrolytes that avoid contact issues and effectively boost the Pmax of n‐ and p‐type thermocell by 76% and 26%, respectively. The optimized thermocell exhibits a quick current density response and is continually fully operational under deformations, which satisfies the working conditions of wearable devices. Multiple thermocells (four pairs) are effectively connected in alternating single n‐ and p‐type cells in series and outputted nearly 74.3 mV at ΔT = 10°C. The wearable device is manufactured into a soft‐pack thermocells to successfully harvest human body heat and illuminate an LED, demonstrating the potential of the actual application of the thermocell devices.

Herbal medicines (HMs) have long played a pivotal role in preventing and treating various human diseases and have been studied widely. However, the complexities present in HM metabolites and their unclear mechanisms of action have posed significant challenges in the modernization of traditional Chinese medicine (TCM). Over the past two decades, mass spectrometry imaging (MSI) has garnered increasing attention as a robust analytical technique that enables the simultaneous execution of qualitative, quantitative, and localization analyses without complex sample pretreatment. With advances in technical solutions, MSI has been extensively applied in the field of HMs. MSI, a label-free ion imaging technique can comprehensively map the spatial distribution of HM metabolites in plant native tissues, thereby facilitating the effective quality control of HMs. Furthermore, the spatial dimension information of small molecule endogenous metabolites within animal tissues provided by MSI can also serve as a supplement to uncover pharmacological and toxicological mechanisms of HMs. In the review, we provide an overview of the three most common MSI techniques. In addition, representative applications in HM are highlighted. Finally, we discuss the current challenges and propose several potential solutions. We hope that the summary of recent findings will contribute to the application of MSI in exploring metabolites and mechanisms of action of HMs.

Background A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC.Methods This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis.Results A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24–0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1–2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size.Conclusion Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study.Trial registration number clinicaltrials.gov, NCT04118855.

Background: Stroke is a debilitating condition with high morbidity, disability, and mortality that significantly affects the quality of life of patients. In China, the WenYang FuYuan recipe is widely used to treat ischemic stroke. However, the underlying mechanism remains unknown, so exploring the potential mechanism of action of this formula is of great practical significance for stroke treatment. Objective: This study employed network pharmacology, molecular docking, and in vivo experiments to clarify the active ingredients, potential targets, and molecular mechanisms of the WenYang FuYuan recipe in cerebral ischemia-reperfusion injury, with a view to providing a solid scientific foundation for the subsequent study of this recipe. Materials and methods: Active ingredients of the WenYang FuYuan recipe were screened using the traditional Chinese medicine systems pharmacology database and analysis platform. Network pharmacology approaches were used to explore the potential targets and mechanisms of action of the WenYang FuYuan recipe for the treatment of cerebral ischemia-reperfusion injury. The Middle Cerebral Artery Occlusion/Reperfusion 2 h Sprague Dawley rat model was prepared, and TTC staining and modified neurological severity score were applied to examine the neurological deficits in rats. HE staining and Nissl staining were applied to examine the pathological changes in rats. Immunofluorescence labeling and Elisa assay were applied to examine the expression levels of certain proteins and associated factors, while qRT-PCR and Western blotting were applied to examine the expression levels of linked proteins and mRNAs in disease-related signaling pathways. Results: We identified 62 key active ingredients in the WenYang FuYuan recipe, with 222 highly significant I/R targets, forming 138 pairs of medication components and component-targets, with the top five being Quercetin, Kaempferol, Luteolin, β-sitosterol, and Stigmasterol. The key targets included TP53, RELA, TNF, STAT1, and MAPK14 (p38MAPK). Targets related to cerebral ischemia-reperfusion injury were enriched in chemical responses, enzyme binding, endomembrane system, while enriched pathways included lipid and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling in diabetic complications. In addition, the main five active ingredients and targets in the WenYang FuYuan recipe showed high binding affinity (e.g. Stigmasterol and MAPK14, total energy

Introduction: The complex geometry of herringbone gear can lead to uneven surface strengthening, which affects the overall effect of treatment. Methods: A discrete element model (DEM) of shot peening for herringbone gears was developed, incorporating accurate gear surface parameters to study impact characteristics along the tooth profile. A finite element model (FEM) was created for small local units of the gear surface to calculate the residual stress and roughness. Results: There are a large number of low-velocity shots at the root of the gear, and the closer to the top of the gear, the higher the impact velocity of the shots, but the number of impacts also decreases. The surface roughness Sa near the root of the tooth is the smallest, the Sa at the pitch circle is the largest, and the Sa at the top of the tooth is intermediate. However, the residual stress levels at different positions of the tooth surface are not significantly different. Conclusion: The difference in tooth surface roughness of herringbone gear is the synergistic effect of shot impact velocity and shot frequency, but this synergistic effect has no significant effect on the stress after shot peening.

Magneto-optical garnet shows great potential in integrated optical isolators due to its highly efficient non-reciprocity. In this work, we prepared magneto-optical lithium-modified terbium bismuth iron garnet films using the liquid phase epitaxy method and systemically investigated the effect of lithium modification on magnetic properties. We found a trace amount of lithium modification induced in-plane magnetization and a minimum in-plane driving field around 2 Oe. Meanwhile, high remanence over 70% was obtained in tensile-strain samples. Most importantly, in comparison to unmodified samples, the calculation of anisotropy demonstrated the giant reduction of growth-induced anisotropy in the Li: TbBiIG up to 105erg/cm3. It reveals a new rule of ions’ preferred occupation in dodecahedral sublattices indirectly. Furthermore, enhanced Faraday rotation in the near-infrared band was confirmed in the samples about 1 micrometer, up to 48% higher than unmodified samples. Our work shows Li:TbBiIGs enable a prime candidate material with substantial potential for integrated optical isolation applications.

Summary: Background: Hospitals in China are classified into tiers (1, 2 or 3), with the largest (tier 3) having more equipment and specialist staff. Differential health insurance cost-sharing by hospital tier (lower deductibles and higher reimbursement rates in lower tiers) was introduced to reduce overcrowding in higher tier hospitals, promote use of lower tier hospitals, and limit escalating healthcare costs. However, little is known about the effects of differential cost-sharing in health insurance schemes on choice of hospital tiers. Methods: In a 9-year follow-up of a prospective study of 0.5 M adults from 10 areas in China, we examined the associations between differential health insurance cost-sharing and choice of hospital tiers for patients with a first hospitalisation for stroke or ischaemic heart disease (IHD) in 2009–2017. Analyses were performed separately in urban areas (stroke: n = 20,302; IHD: n = 19,283) and rural areas (stroke: n = 21,130; IHD: n = 17,890), using conditional logit models and adjusting for individual socioeconomic and health characteristics. Findings: About 64–68% of stroke and IHD cases in urban areas and 27–29% in rural areas chose tier 3 hospitals. In urban areas, higher reimbursement rates in each tier and lower tier 3 deductibles were associated with a greater likelihood of choosing their respective hospital tiers. In rural areas, the effects of cost-sharing were modest, suggesting a greater contribution of other factors. Higher socioeconomic status and greater disease severity were associated with a greater likelihood of seeking care in higher tier hospitals in urban and rural areas. Interpretation: Patient choice of hospital tiers for treatment of stroke and IHD in China was influenced by differential cost-sharing in urban areas, but not in rural areas. Further strategies are required to incentivise appropriate health seeking behaviour and promote more efficient hospital use. Funding: Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and National Natural Science Foundation of China.

Summary: Pathogenic mycobacteria orchestrate the complex cell populations known as granuloma that is the hallmark of tuberculosis. Foam cells, a lipid-rich cell-type, are considered critical for granuloma formation; however, the causative factor in foam cell formation remains unclear. Atherosclerosis is a chronic inflammatory disease characterized by the abundant accumulation of lipid-laden-macrophage-derived foam cells during which cholesterol 25-hydroxylase (CH25H) is crucial in foam cell formation. Here, we show that M. marinum (Mm), a relative of M. tuberculosis, induces foam cell formation, leading to granuloma development following CH25H upregulation. Moreover, the Mm-driven increase in CH25H expression is associated with the presence of phthiocerol dimycocerosate, a determinant for Mm virulence and integrity. CH25H-null mice showed decreased foam cell formation and attenuated pathology. Atorvastatin, a recommended first-line lipid-lowering drug, promoted the elimination of M. marinum and concomitantly reduced CH25H production. These results define a previously unknown role for CH25H in controlling macrophage-derived foam cell formation and Tuberculosis pathology.

Ischemic stroke and vascular dementia, as common cerebrovascular diseases, with the former causing irreversible neurological damage and the latter causing cognitive and memory impairment, are closely related and have long received widespread attention. Currently, the potential causative genes of these two diseases have yet to be investigated, and effective early diagnostic tools for the diseases have not yet emerged. In this study, we screened new potential biomarkers and analyzed new therapeutic targets for both diseases from the perspective of immune infiltration. Two gene expression profiles on ischemic stroke and vascular dementia were obtained from the NCBI GEO database, and key genes were identified by LASSO regression and SVM-RFE algorithms, and key genes were analyzed by GO and KEGG enrichment. The CIBERSORT algorithm was applied to the gene expression profile species of the two diseases to quantify the 24 subpopulations of immune cells. Moreover, logistic regression modeling analysis was applied to illustrate the stability of the key genes in the diagnosis. Finally, the key genes were validated using RT-PCR assay. A total of 105 intersecting DEGs genes were obtained in the 2 sets of GEO datasets, and bioinformatics functional analysis of the intersecting DEGs genes showed that GO was mainly involved in the purine ribonucleoside triphosphate metabolic process，respiratory chain complex，DNA−binding transcription factor binding and active transmembrane transporter activity. KEGG is mainly involved in the Oxidative phosphorylation, cAMP signaling pathway. The LASSO regression algorithm and SVM-RFE algorithm finally obtained three genes, GAS2L1, ARHGEF40 and PFKFB3, and the logistic regression prediction model determined that the three genes, GAS2L1 (AUC: 0.882), ARHGEF40 (AUC: 0.867) and PFKFB3 (AUC: 0.869), had good diagnostic performance. Meanwhile, the two disease core genes and immune infiltration were closely related, GAS2L1 and PFKFB3 had the highest positive correlation with macrophage M1 (p

Abstract Surface electromyography (sEMG) is widely used in monitoring human health. Nonetheless, it is challenging to capture high-fidelity sEMG recordings in regions with intricate curved surfaces such as the larynx, because regular sEMG electrodes have stiff structures. In this study, we developed a stretchable, high-density sEMG electrode array via layer-by-layer printing and lamination. The electrode offered a series of excellent human‒machine interface features, including conformal adhesion to the skin, high electron-to-ion conductivity (and thus lower contact impedance), prolonged environmental adaptability to resist water evaporation, and epidermal biocompatibility. This made the electrode more appropriate than commercial electrodes for long-term wearable, high-fidelity sEMG recording devices at complicated skin interfaces. Systematic in vivo studies were used to investigate its ability to classify swallowing activities, which was accomplished with high accuracy by decoding the sEMG signals from the chin via integration with an ear-mounted wearable system and machine learning algorithms. The results demonstrated the clinical feasibility of the system for noninvasive and comfortable recognition of swallowing motions for comfortable dysphagia rehabilitation.

Abstract Josephson tunneling in twisted cuprate junctions provides a litmus test for the pairing symmetry, which is fundamental for understanding the microscopic mechanism of high temperature superconductivity. This issue is rekindled by experimental advances in van der Waals stacking and the proposal of an emergent d+id-wave. So far, all experiments have been carried out on Bi2Sr2CaCu2O8+x (Bi-2212) with double CuO2 planes but show controversial results. Here, we investigate junctions made of Bi2Sr2-xLaxCuO6+y (Bi-2201) with single CuO2 planes. Our on-site cold stacking technique ensures uncompromised crystalline quality and stoichiometry at the interface. Junctions with carefully calibrated twist angles around 45° show strong Josephson tunneling and conventional temperature dependence. Furthermore, we observe standard Fraunhofer diffraction patterns and integer Fiske steps in a junction with a twist angle of 45.0±0.2°. Together, these results pose strong constraints on the d or d+id-wave pairing and suggest an indispensable isotropic pairing component.

Purposes K-ion batteries (KIBs) have attracted considerable attention as a potential alternative to Li-ion batteries because of their low cost and high energy density. However, the development of KIBs has been severely limited by the lack of cathodes with high specific capacity and good cycle performance. Methods In this research, P3-type K0.5MnO2 as a new cathode material for KIBs was prepared through hydrothermal method, sol-gel method, and oxalate co-precipitation method, separately. Conclustions It is shown that K0.5MnO2 synthesized through the hydrothermal precursor method (denoted as H-K0.5MnO2) has a rough surface and more internal pores, which are beneficial to electron transfer and can provide more active sites. At a specific current of 20 mA/g, H-K0.5MnO2 electrode can achieve the highest first discharge specific capacity of 85 mAh/g. XRD and EIS results of the H-K0.5MnO2 electrodes after 60 cycles demonstrate that H-K0.5MnO2 still maintains the most stable structure and has the smallest charge transfer resistance, leading to a desirable capacity retention. The potassium-ions storage properties indicate that the pseudo-capacitance accounts for the highest proportion in H-K0.5MnO2 at a high rate, enabling fast reversible charge-discharge.

Abstract Background Previous observational studies have found an association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases, but it remains uncertain whether GERD causally influences these diseases. In this study, we aimed to estimate the causal associations between GERD and 5 chronic respiratory diseases. Methods 88 GERD-associated single nucleotide polymorphisms (SNPs) identified by the latest genome-wide association study were included as instrumental variables. Individual-level genetic summary data of participants were obtained from corresponding studies and the FinnGen consortium. We applied the inverse-variance weighted method to estimate the causality between genetically predicted GERD and 5 chronic respiratory diseases. Furthermore, the associations between GERD and common risk factors were investigated, and mediation analyses were conducted using multivariable MR. Various sensitivity analyses were also performed to verify the robustness of the findings. Results Our study demonstrated that genetically predicted GERD was causally associated with an increased risk of asthma (OR 1.39, 95%CI 1.25–1.56, P

Abstract Background Metabolic derangements and systemic inflammation are related to the progression of colorectal cancer (CRC) and the prognoses of these patients. The survival of stage II and III CRC patients existed considerable heterogeneity highlighting the urgent need for new prediction models. This study aimed to develop and validate prognostic nomograms based on preoperative serum liver enzyme as well as evaluate the clinical utility. Methods A total of 4014 stage II/III primary CRC patients pathologically diagnosed from January 2007 to December 2013 were included in this study. These patients were randomly divided into a training set (n = 2409) and a testing set (n = 1605). Univariate and multivariate Cox analyses were used to select the independent factors for predicting overall survival (OS) and disease-free survival (DFS) of stage II/III CRC patients. Next, nomograms were constructed and validated to predict the OS and DFS of individual CRC patients. The clinical utility of nomograms, tumor-node-metastasis (TNM), and the American Joint Committee on Cancer (AJCC) system was evaluated using time-dependent ROC and decision curve analyses. Results Among seven preoperative serum liver enzyme markers, aspartate aminotransferase-to-alanine aminotransferase ratio (De Ritis ratio) was identified as an independent factor for predicting both OS and DFS of stage II/III CRC patients. The nomograms incorporated De Ritis ratio and significant clinicopathological features achieved good accuracy in terms of OS and DFS prediction, with C-index of 0.715 and 0.692, respectively. The calibration curve showed good agreement between prediction by nomogram and actual observation. The results of time-dependent ROC and decision curve analyses suggested that the nomograms had improved discrimination and greater clinical benefits compared with TNM and AJCC staging. Conclusions De Ritis ratio was an independent predictor in predicting both the OS and DFS of patients with stage II/III CRC. Nomograms based on De Ritis ratio and clinicopathological features showed better clinical utility, which is expected to help clinicians develop appropriate individual treatment strategies for patients with stage II /III CRC.

Abstract Immunogenic cell death (ICD) is a form of cell death that stimulates the immune system to produce an immune response by releasing tumour-associated antigens and tumour-specific antigens and is considered to play an important role in tumour immunotherapy. In the present study, we identified two ICD-related subtypes in osteosarcoma (OS) by consensus clustering. The ICD-low subtype was associated with favourable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signalling. We also established and validated an ICD-related prognostic model, which could not only be used to predict the overall survival of OS patients but was also found to be closely related to the tumour immune microenvironment of OS patients. Overall, we established a new classification system for OS based on ICD-related genes, which can be used to predict the prognosis of OS patients and to select appropriate immunotherapy drugs.

Sodium‐ion batteries (SIBs) have attracted attention due to their potential applications for future energy storage devices. Despite significant attempts to improve the core electrode materials, only some work has been conducted on the chemistry of the interface between the electrolytes and essential electrode materials. Therefore, the different cathode–electrolyte interfaces (CEIs) that form between various cathode materials and liquid electrolytes for SIBs are briefly reviewed, and the requirements of CEI performance in low‐temperature SIBs. Modifying the cathode materials and electrolyte formulas offers an efficient strategy for CEI enhancement. The summary and analysis, given in this article, may serve as a reference for the development of better sodium‐ion batteries.

IntroductionGranulomas, the pathological hallmark of Mycobacterium tuberculosis (Mtb) infection, are formed by different cell populations. Across various stages of tuberculosis conditions, most granulomas are classical caseous granulomas. They are composed of a necrotic center surrounded by multilayers of histocytes, with the outermost layer encircled by fibrosis. Although fibrosis characterizes the architecture of granulomas, little is known about the detailed parameters of fibrosis during this process.MethodsIn this study, samples were collected from patients with tuberculosis (spanning 16 organ types), and Mtb-infected marmosets and fibrotic collagen were characterized by second harmonic generation (SHG)/two-photon excited fluorescence (TPEF) microscopy using a stain-free, fully automated analysis program.ResultsHistopathological examination revealed that most granulomas share common features, including necrosis, solitary and compact structure, and especially the presence of multinuclear giant cells. Masson’s trichrome staining showed that different granuloma types have varying degrees of fibrosis. SHG imaging uncovered a higher proportion (4%~13%) of aggregated collagens than of disseminated type collagens (2%~5%) in granulomas from matched tissues. Furthermore, most of the aggregated collagen presented as short and thick clusters (200~620 µm), unlike the long and thick (200~300 µm) disseminated collagens within the matched tissues. Matrix metalloproteinase-9, which is involved in fibrosis and granuloma formation, was strongly expressed in the granulomas in different tissues.DiscussionOur data illustrated that different tuberculosis granulomas have some degree of fibrosis in which collagen strings are short and thick. Moreover, this study revealed that the SHG imaging program could contribute to uncovering the fibrosis characteristics of tuberculosis granulomas.

Green hydrogen production through the electrocatalytic hydrogen evolution reaction (HER) is a promising solution for transition from fossil fuels to renewable energy. To enable the use of a variety of electrolytes with different pH values, HER catalysts with pH universality are highly desirable but their performance remains mediocre. Herein, a pH‐universal HER catalyst composed of ruthenium nanoparticles decorated on amorphous Ni‐doped MoO3 (a–Ni–MoO3) nanowire support is reported, that is, Ru/a–Ni–MoO3, which achieves enhanced performance as compared to the commercial Ru/C catalyst. Electron transfer from Ru to a–Ni–MoO3 is identified by spectroscopic techniques, which results in a modified electronic structure of the Ru active sites with a reduced electron density of 4d states near the Fermi level. Density functional theory calculations further reveal that the modulated electronic structure weakens the interactions between the Ru active sites and the reaction intermediates, which facilitates the HER reaction steps including H intermediate desorption and water dissociation. Experimental and theoretical findings provide insight into enhancing pH‐universal HER performance through modulation of electrocatalyst electronic structure.

ABSTRACT Endoribonuclease non-structural protein 15 (nsp15) (EndoU) is conserved among coronaviruses (CoVs) and is crucial for viral replication, evasion of the innate immune system, and virulence. EndoU-deficient CoVs can activate the interferon (IFN) response and attenuate their virulence, and nsp15 is considered the target of attenuated vaccine development. Among alpha-CoVs, transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) cause lethal diseases in piglets and cats, but the role of EndoU in viral propagation and virulence remains unclear. Here, we verified the TGEV and FIPV EndoU active sites His226 and His241 and found that the antagonization of SeV-induced IFN-β production by nsp15 depends on its EndoU activity. Furthermore, we constructed infectious clones of wild-type (WT) and EndoU-deficient (EnUmt) TGEV and FIPV. Unexpectedly, we found that both the WT and EnUmt viruses propagated efficiently in multiple types of immunocompetent (PK-15, IPI-2I, ST, CRFK, F81, and Fcwf-4) cells. Moreover, the results of infection experiments showed that compared with piglets and cats infected with the WT, the EnUmt virus-infected piglets and cats did not exhibit significantly reduced mortality, tissue injury, or viral shedding. Specially, the death of cats infected with EnUmt-FIPV occurred earlier than that of cats infected with WT. Hence, our results suggest that the function of EndoU is conserved, but nsp15-mediated regulation of the propagation and pathogenesis of CoVs are diverse. Our findings provide a reference for an in-depth understanding of EndoU-mediated immune escape and pathogenicity in CoVs. IMPORTANCE Understanding the role of the endoribonuclease non-structural protein 15 (nsp15) (EndoU) in coronavirus (CoV) infection and pathogenesis is essential for vaccine target discovery. Whether the EndoU activity of CoV nsp15, as a virulence-related protein, has a diverse effect on viral virulence needs to be further explored. Here, we found that the transmissible gastroenteritis virus (TGEV) and feline infectious peritonitis virus (FIPV) nsp15 proteins antagonize SeV-induced interferon-β (IFN-β) production in human embryonic kidney 293 cells. Interestingly, compared with wild-type infection, infection with EnUmt-TGEV or EnUmt-FIPV did not change the IFN-β response or reduce viral propagation in immunocompetent cells. The results of animal experiments showed that EnUmt viruses did not reduce the clinical presentation and mortality caused by TGEV and FIPV. Our findings enrich the understanding of nsp15-mediated regulation of alpha-CoV propagation and virulence and reveal that the conserved functions of nonstructural proteins have diverse effects on the pathogenicity of CoVs.

Abstract Background Pemphigus vulgaris (PV) is a kind of rare and severe autoimmune bullous disease. In this case, the specificity of oral PV lies in the clinical manifestations of a single palatal ulcer, and no blisters were found in the oral mucosa. This case provides a powerful reference for dentists diagnosing and treating oral PV with atypical clinical presentations. Case presentation A 54 years old female patient presented with a non-healing palatal gingival ulcer for over three months. By histopathological H&E staining and the direct immunofluorescence (DIF) test, the final diagnosis was oral PV. After topical glucocorticoid therapy, the affected area was cured. Conclusions In patients with prolonged erosion of the skin or oral mucosa, even if complete blisters are not visible, the physician should consider autoimmune bullous diseases and pay attention to avoid diagnostic defects.

Objective: Previous studies are insufficient to confirm a causal association between physical activity (PA) and low back pain (LBP), intervertebral disc degeneration (IDD), and sciatica. The present study used a two-sample Mendelian randomization (MR) analysis method to demonstrate whether or not there was a causal connection.Methods: First, four PA phenotypes were selected [accelerometer-based PA (average acceleration), accelerometer-based PA (acceleration fraction >425 mg), self-reported moderate-to-vigorous PA, and self-reported vigorous PA], setting thresholds for single nucleotide polymorphisms (SNPs) significantly concerned with PA p < 5 × 10−8, linkage disequilibrium (LD) r2 < 0.01, genetic distance >5,000 kb, and F-value >10. SNPs associated with the outcome and confounding factors were then excluded using the PhenoScanncer database. Finally, after coordinating the genetic instruments from genome-wide association studies (GWAS) effect alleles for exposure and outcomes, multiplicative random effects inverse variance weighting (IVW), MR-Egger, weighted median method (WMM), and weighted mode method were used to assess exposure-outcome causality and perform sensitivity analysis on the estimated results.Results: The current study’s IVW findings revealed proof of a causal connection between PA and LBP. While there was a positive causal tie between accelerometer-based PA (acceleration fraction >425 mg) and LBP [OR: 1.818, 95% CI:1.129–2.926, p = 0.012], there was a negative causal link between accelerometer-based PA (average acceleration) and LBP [OR: 0.945, 95% CI: 0.909–0.984, p = 0.005]. However causal relationship between PA and IDD or sciatica was not found.Conclusion: Increasing average PA but needing to avoid high-intensity PA may be an effective means of preventing low back pain. Although PA is not directly causally related to disc degeneration and sciatica, it can act through indirect pathways.

Abstract High‐capacity O3‐type layered sodium oxides are considered one of the most promising cathode materials for the next generation of Na‐ion batteries (NIBs). However, these cathodes usually suffer from low high‐rate capacity and poor cycling stability due to structure deformation, native air sensitivity, and interfacial side reactions. Herein, a multi‐site substituted strategy is employed to enhance the stability of O3‐type NaNi0.5Mn0.5O2. Simulations indicate that the Ti substitution decreases the charge density of Ni ions and improves the antioxidative capability of the material. In addition, the synergistic effect of K+ and Ti4+ significantly reduces the formation energy of Na+ vacancy and delivers an ultra‐low lattice strain during the repeated Na+ extraction/insertion. In situ characterizations verify that the complicated phase transformation is mitigated during the charge/discharge process, resulting in greatly improved structure stability. The co‐substituted cathode delivers a high‐rate capacity of 97 mAh g−1 at 5 C and excellent capacity retention of 81% after 400 cycles at 0.5 C. The full cell paired with commercial hard carbon anode also exhibits high capacity and long cycling life. This dual‐ion substitution strategy will provide a universal approach for the new rational design of high‐capacity cathode materials for NIBs.

Compared with hydrogen evolution reaction (HER) under acidic conditions, the kinetic steps of alkaline HER are more complex, which involves the adsorption and cleavage of water molecules. Defect and interface engineering are two important means to enhance basic HER. In order to prepare catalysts with high activity and stability under both acidic and basic conditions, a defective amorphous carbon loaded with Ru nanoparticles coaxially wrapped around a carbon nanotube (CNT) sponge network is presented. The presence of amorphous carbon can promote the uniform loading of Ru nanoparticles and limit the growth of Ru nanoparticles, and also the introduction of oxygen defects can regulate the electronic structure of the metal and improve its charge transport capacity, thus enhancing the catalytic performance. The catalyst CNT/C/Ru0.37 wt%‐700 prepared under optimized conditions exhibits excellent stability and activity. At a current density of 10 mA cm−2, the overpotential of HER is as low as 38.3 and 36.2 mV under alkaline and acidic conditions, respectively, which is better than most reported Ru‐based catalysts. This study details innovative and feasible ideas for the design and preparation of loaded catalysts, which can contribute to the development of high‐performance electrochemical catalysts.

Background: Inflammation plays a crucial role in the initiation and progression of cerebral ischemia-reperfusion injury and has gained much scholarly interest. However, this research field has not yet been examined bibliometrically. We intended to utilize bibliometrics to highlight the research hotspots and developing trends of inflammation in cerebral ischemia-reperfusion injury and provide an objective foundation for basic and clinical research. Methods: The Web of Science database was combed for articles relating to inflammation in cerebral ischemia-reperfusion injury from 2002 to 2022. CiteSpace and VOSviewer were used to visualize and analyze data pertaining to countries, institutions, journals, authors, references, and keywords. Results: There were a total of 1183 papers included in this analysis. Every year, the number of articles on inflammation research in cerebral ischemia-reperfusion injury increases. Brain Research and Stroke are, respectively, the most published and most cited academic journals in this discipline. We identified 646 scholars, with Zhao,jing producing the most publications and Longa EZ receiving the most citations. Inflammation, stroke, oxidative stress, and apoptosis were found to be the most frequently used terms after analysis. The main areas of current research on inflammation in cerebral ischemia-reperfusion injury involve non-coding rna, myeloperoxidase, Toll-like receptor-4, and neurotrophic factor. Conclusion: The importance of inflammation in cerebral ischemia-reperfusion injury diseases has been widely recognized. After decades of constant research, we are not yet sufficiently knowledgeable in this sector.Microglial activation, signaling pathway, protection and pathophysiology will be the new hot and new direction in this research field in the future.

Abstract Acute ischemic stroke (AIS) induces high level of neutrophils, which correlates inversely with patient survival. Pyroptosis induced by gasdermin D (GSDMD) has been shown to have an important role in the pathophysiology of several inflammatory disorders. The role of GSDMD in the high level of neutrophils after AIS is unknown. Using a middle cerebral artery occlusion (MCAO) mouse model, we identified activation of pyroptosis signal, including expression of caspase-1/11, GSDMD, and interleukin-1β/18 (IL-1β/18), in the brain and spleen at early ischemic injury. Knockout of GSDMD in mice reduced infarct size, improved neurological function, and increased survival after MCAO. GSDMD deficiency decreased the overall degree of inflammation and the proportion of neutrophils in the brain after MCAO. Quantitative studies of neutrophils at several time intervals and organs demonstrated that early inflammatory leucocyte production and supplement (1 day after MCAO) was GSDMD-dependent. A series of bone marrow transplantation experiments, neutrophil depletion experiments, and RNA sequencing results demonstrated that neutrophil specific GSDMD is essential for the production and supply of neutrophil in bone marrow to blood. Moreover, pharmacological suppression of GSDMD decreased pathological abnormalities, infarct volume, and ameliorated neurological function. These results provided a new viewpoint on the immunological modulation of neutrophils after MCAO and suggest that suppression of GSDMD may relieve the neuroinflammatory load, thereby providing a potential treatment strategy for stroke. The absence of GSDMD reduces the high level of neutrophils in the brain, the production of neutrophils in bone marrow, and the supply of blood and spleen, while simultaneously the neutrophil-specific GSDMD signal deficiency restrains leukocytosis to improve the pathological outcome of AIS.

Abstract Postoperative pain (POP) can promote tumor recurrence and reduce the cancer patient's quality of life. However, POP management has always been separated from tumor treatment in clinical practice, and traditional postoperative analgesia using opioids is still unsatisfactory for patients, which is not conducive to tumor treatment. Here, ropivacaine, a popular amide-type LA, was introduced into a Pluronic F127 hydrogel. Postoperative analgesia with ropivacaine-loaded hydrogels reduced the incidence of high-dose ropivacaine-induced convulsions and prolonged pain relief for more than 16 h. More interestingly, ropivacaine-loaded hydrogel was found to upregulate major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-dopped with ropivacaine and TLR7 agonist imiquimod (PFRM) was rationally synthesized. After postoperative analgesia with PFRM, imiquimod primes tumor-specific CD8+T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+T cells through upregulating MHC-I. Consequently, postoperative analgesia with PFRM maximumly increases CD8+T cells infiltration into residual tumor tissue and prevents tumor recurrence. Overall, this study for the first time provides an LA-based approach for simultaneous long-lasting postoperative analgesia and prevention of tumor recurrence.

Abstract In modern era, the maintenance of public infrastructure often takes up a large share of financial budget for a city. The management of these urban assets is supported by a frequently updated inventory reflecting facility conditions. Traditional methods relying on inspection staff or sensors are faced with two main challenges: comprehensive and standardized data collection; quick and automatic assessment process. In this technical note, we introduce a unified method for condition assessment, purely based on street views and machine learning to develop perception quantification models with pairwise labeling datasets. In this way, the two problems could be solved with automatic and scalable processes, updatable algorithms, and affordable costs The method has been tested in the city of Ulaanbaatar, in which a benchmark covering the assessment of eight types of urban infrastructure (roadway, road curbs, road markings, road signs, sidewalks, catch basins, guardrails, and manholes) is demonstrated.

BackgroundThe incidence and mortality rates of stroke are escalating due to the growing aging population, which presents a significant hazard to human health. In the realm of stroke, brain-computer interface (BCI) technology has gained considerable attention as a means to enhance treatment efficacy and improve quality of life. Consequently, a bibliometric visualization analysis was performed to investigate the research hotspots and trends of BCI technology in stroke, with the objective of furnishing reference and guidance for future research.MethodsThis study utilized the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as the data source, selecting relevant literature published between 2013 and 2022 as research sample. Through the application of VOSviewer 1.6.19 and CiteSpace 6.2.R2 visualization analysis software, as well as the bibliometric online analysis platform, the scientific knowledge maps were constructed and subjected to visualization display, and statistical analysis.ResultsThis study encompasses a total of 693 relevant literature, which were published by 2,556 scholars from 975 institutions across 53 countries/regions and have been collected by 185 journals. In the past decade, BCI technology in stroke research has exhibited an upward trend in both annual publications and citations. China and the United States are high productivity countries, while the University of Tubingen stands out as the most contributing institution. Birbaumer N and Pfurtscheller G are the authors with the highest publication and citation frequency in this field, respectively. Frontiers in Neuroscience has published the most literature, while Journal of Neural Engineering has the highest citation frequency. The research hotspots in this field cover keywords such as stroke, BCI, rehabilitation, motor imagery (MI), motor recovery, electroencephalogram (EEG), neurorehabilitation, neural plasticity, task analysis, functional electrical stimulation (FES), motor impairment, feature extraction, and induced movement therapy, which to a certain extent reflect the development trend and frontier research direction of this field.ConclusionThis study comprehensively and visually presents the extensive and in-depth literature resources of BCI technology in stroke research in the form of knowledge maps, which facilitates scholars to gain a more convenient understanding of the development and prospects in this field, thereby promoting further research work.

BackgroundSystemic inflammation is associated with the prognosis of colorectal cancer (CRC). The current study aimed to construct a comprehensively inflammatory prognostic scoring system named risk score (RS) based on eosinophil- and basophil-related markers and assess its prognostic value in patients with stage II and stage III CRC.Patients and methodsA total of 3,986 patients were enrolled from January 2007 to December 2013. The last follow-up time was January 2019. They were randomly assigned to the training set and testing set in a 3:2 split ratio. Least absolute shrinkage and selection operator (LASSO)–Cox regression analysis was performed to select the optimal prognostic factors in the construction of RS. The Kaplan–Meier curve, time-dependent receiver operating characteristic (ROC), and Cox analysis were used to evaluate the association between RS and overall survival (OS).ResultsIn the training set, all inflammatory markers showed certain prognostic values. Based on LASSO-Cox analysis, nine markers were integrated to construct RS. The Kaplan–Meier curve showed that a higher RS (RS > 0) had a significantly worse prognosis (log-rank p< 0.0001). RS (>0) remained an independent prognostic factor for OS (hazard ratio (HR): 1.70, 95% confidence interval (CI), 1.43–2.03, p< 0.001). The prognostic value of RS was validated in the entire cohort. Time-dependent ROC analysis showed that RS had a stable prognostic effect throughout the follow-up times and could enhance the prognostic ability of the stage by combination. Nomogram was established based on RS and clinicopathological factors for predicting OS in the training set and validated in the testing set. The area under the curve (AUC) values of the 3-year OS in the training and testing sets were 0.748 and 0.720, respectively. The nomogram had a satisfactory predictive accuracy and had better clinical application value than the tumor stage alone.ConclusionsRS might be an independent prognostic factor for OS in patients with stage II and III CRC, which is helpful for risk stratification of patients. Additionally, the nomogram might be used for personalized prediction and might contribute to formulating a better clinical treatment plan.

The ability to rapidly and accurately delineate open-pit granite mining areas is pivotal for effective production planning and environmental impact assessment. Over the years, advancements in remote sensing techniques, including the utilization of satellite imagery, LiDAR technology and unmanned aerial vehicles, have revolutionized the way mining areas are monitored and managed. Simultaneously, in the context of the open-pit mining area extraction task, deep learning-based automatic recognition is gradually replacing manual visual interpretation. Leveraging the potential of unmanned aerial vehicles (UAVs) for real-time, low-risk remote sensing, this study employs UAV-derived orthophotos for mining area extraction. Central to the proposed approach is the novel Gather–Injection–Perception (GIP) module, designed to overcome the information loss typically associated with conventional feature pyramid modules during feature fusion. The GIP module effectively enriches semantic features, addressing a crucial information limitation in existing methodologies. Furthermore, the network introduces the Boundary Perception (BP) module, uniquely tailored to tackle the challenges of blurred boundaries and imprecise localization in mining areas. This module capitalizes on attention mechanisms to accentuate critical high-frequency boundary details in the feature map and synergistically utilizes both high- and low-dimensional feature map data for deep supervised learning. The suggested method demonstrates its superiority in a series of comparative experiments on a specially assembled dataset of research area images. The results are compelling, with the proposed approach achieving 90.67% precision, 92.00% recall, 91.33% F1-score, and 84.04% IoU. These figures not only underscore the effectiveness of suggested model in enhancing the extraction of open-pit granite mining areas but also provides a new idea for the subsequent application of UAV data in the mining scene.

The failures of diaphragm couplings in application are mostly originated from fatigue failures of the diaphragm. To improve the fatigue performance of the diaphragm coupling，a optimization design method for the diaphragm profile parameters based on the Kriging model is proposed to maximize the high-cycle fatigue safety factor of the diaphragm design. After analyzing the structure of the diaphragm profile and the feature of the high-cycle fatigue stress for the diaphragm under various loads，the sample data of the high-cycle fatigue safety factors for groups of diaphragm profile parameters （including outside/inside radius ratio，profile index and minimum thickness） are obtained，and an initial Kriging model is then constructed on the basis of these sample data. Finally，the initial Kriging model is updated with MP （minimizing the predicted objective function） infill-sampling criterion and genetic algorithm，and the optimal design is obtained via the final Kriging model. The proposed method is then utilized to optimize the profile design of a diaphragm in a helicopter transmission system，and the results show that the static stress and dynamic stress of the critical point for the optimized diaphragm are decreased by 18.7% and 40.7% respectively compared with the original diaphragm design，and thus the high-cycle fatigue safety factor of the optimized diaphragm is increased by 52.8%. The proposed method can be used to improve the fatigue performance of the diaphragm，which provides a reference for the design of the diaphragm profile.

Summary: Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a progressive and disturbing peripheral neuropathy with currently no effective treatment. Aberrant production of reactive oxygen species (ROS) in macrophages near peripheral nerves plays a dominant role in CIPNP; however, traditional ROS scavengers have difficulty maintaining viability to target macrophages in vivo. Mannose-coated superparamagnetic iron oxide nanoparticles (mSPIONs) were synthesized to treat CIPNP. The anti-ROS and anti-inflammatory effects of mSPIONs were assessed in J774A.1 cells and sciatic nerves in a nociception mouse model induced with vincristine (VCR). We found that the mSPIONs significantly reduced ROS levels in vitro and in vivo. Furthermore, mSPIONs administration specifically reduced IL-6 and TNF-α levels in macrophages near the sciatic nerve and relieved VCR-induced peripheral neuropathic pain. Inhibition of the VCR-upregulated HIF1α/NF-κB signaling pathway may be involved in the alleviation of inflammation. These results provide a new approach for relieving CIPNP using a nanozyme.

Bone marrow mesenchymal stem cells (BMSCs) can repair spinal cord ischemia-reperfusion injury (SCII); however, only a few BMSCs are usually located in the injured spinal cord. Since the brain-derived neurotrophic factor (BDNF) can promote neural development and maturation, we hypothesised that BDNF-overexpressed BMSCs can ameliorate SCII more effectively than BMSCs alone. To determine the effect of BDNF overexpression on SCII repair, BDNF-overexpressed BMSCs and BMSCs were transplanted into SCII rats. Our results revealed that BDNF-overexpressed BMSCs can better promote the recovery of damaged spinal cords than BMSCs alone. Gene chip detection of spinal cord tissues showed 803 differentially expressed genes in all groups. BTG anti-proliferation factor 2 (Btg2), FOS like 2 (Fosl2), early growth response protein 1 (Egr1), and serpin family E member 1 (Serpine1) were identified as key interrelated genes based on their expression trends, as validated via quantitative PCR and protein–protein interaction network analysis. A co-expression network was constructed to further explore the role of the candidate key genes using Pearson correlation analysis. Cluster 5 was identified as the key cluster using community discovery algorithms. Functional analysis of Cluster 5 genes revealed that this cluster was mainly involved in the stress-activated MAPK cascade, p38MAPK cascade, and apoptosis. Notably, Egr1 may play an important role in SCII repair as the top hub gene in Cluster 5. Therefore, the repair activity of transplanted BDNF-overexpressed BMSCs in SCII rats is better than that of BMSCs alone, which may be regulated by the interactions between Btg2, Fosl2, Egr1, Serpine1, and BDNF.

Electrocaloric (EC) cooling technology has emerged as a powerful candidate for the next-generation cooler. Microfluidic EC cooling device could directly be embedded inside microelectronics to build up a highly efficient thermal management system. However, the microfluidic EC cooling device with large temperature lift still remains a big challenge. Here, we prepared a high-performance cascade EC cooling tube with multistage cooling accumulation and improved its cooling power by sawtooth voltage. The cascade EC tube realized a maximum temperature drop of 4.6 K. A maximum temperature span of 4.2 K was obtained when the flow velocity of liquid medium is 10 mm/s. A continuous sub-ambient liquid medium with improved cooling power can be achieved after the cascade EC tube cycle loading with sawtooth voltage. This high-performance cascade EC tube provides a sub-ambient liquid medium, opening up a unique way to enhance the cooling power and realize multistage cooling accumulation. It demonstrates the great application potential in smart thermal management of microelectronic systems.

Background & aimsLittle is known about molecular biomarkers that predict the response and prognosis in unresectable hepatocellular carcinoma (HCC) treated with programmed death (PD)-1 inhibitors.MethodsA total of 62 HCC patients who underwent next-generation sequencing were retrospectively included in our department for this study. Patients with unresectable disease were subjected to systemic therapy. PD-1 inhibitors intervention (PD-1Ab) group and nonPD-1Ab group included 20 and 13 patients, respectively. Primary resistance was defined as initial on-treatment progression or progression with an initial stable disease of less than 6 months.ResultsChromosome 11q13 amplification (Amp11q13) was the most common copy number variation in our cohort. Fifteen (24.2%) patients harbored Amp11q13 in our dataset. Patients with Amp11q13 showed higher level of Des-γ-carboxy-prothrombin (DCP), tumor number and were more prone to be combined with portal vein tumor thrombosis (PVTT). In the PD-1Ab group, the proportion of progressive disease (PD) in patients with Amp11q13 was significantly higher than that in patients with nonAmp11q13 (100% vs 33.3%, P=0.03). In the nonPD-1Ab group, the proportion of PD in patients with Amp11q13 and nonAmp11q13 had no significant difference (0% vs 11.1%, P>0.99). In the PD-1Ab group, the median progression-free survival (PFS) was 1.5 months in Amp11q13 patients vs 16.2 months in non-Amp11q13 patients (HR, 0.05; 95% CI 0.01-0.45; P = 0.0003). No significant difference was observed in the nonPD-1Ab group. Notably, we found that hyperprogressive disease (HPD) might be associated with Amp11q13. The increased density of Foxp3+ Treg cells in HCC patients with Amp11q13 might be one of potential mechanisms.ConclusionHCC patients with Amp11q13 are less likely to benefit from PD-1 blockade therapies. These findings may help guide the use of immunotherapy for HCC in routine clinical practice.

Abstract Background In non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs), higher blood tumor mutational burden (bTMB) was usually associated with better progression-free survival (PFS) and objective response rate (ORR). However, the association between bTMB and overall survival (OS) benefit remains undefined. It has been reported that patients harboring a high level of circulating tumor DNA (ctDNA) had poor survival. We hypothesized that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs. Methods Our study was retrospectively performed in three cohorts, including OAK and POPLAR cohort (n = 853), Shanghai and Wuhan (SH&WH) cohort (n = 44), and National Cancer Center (NCC) cohort (n = 47). Durable clinical benefit (DCB) was defined as PFS lasting ≥ 6 months. The cutoff value of ctDNA-adjusted bTMB for DCB prediction was calculated based on a receiver operating characteristic curve. Interaction between treatments and ctDNA-adjusted bTMB was assessed. Results The bTMB score was significantly associated with tumor burden, while no association was observed between ctDNA-adjusted bTMB with tumor burden. In the OAK and POPLAR cohort, significantly higher ORR (P = 0.020) and DCB (P

Understanding the rich electronic orders in cuprate superconductors provide insights into the mechanism of high-temperature superconductivity. Here, the authors report a distinct charge order with Little-Parks like resistance oscillations at magnetic fields up to 10 T and around T c in lightly doped Bi2Sr2CaCu2O8+x .