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Abstract Background The role of Claudin‐1 in tongue squamous cell carcinoma (TSCC) metastasis needs further clarification, particularly its impact on cell migration. Herein, our study aims to investigate the role of Claudin‐1 in TSCC cell migration and its underlying mechanisms. Methods 36 TSCC tissue samples underwent immunohistochemical staining for Claudin‐1. Western blotting and immunofluorescence analyses were conducted to evaluate Claudin‐1 expression and distribution in TSCC cells. Claudin‐1 knockdown cell lines were established using short hairpin RNA transfection. Migration effects were assessed through wound healing assays. Furthermore, the expression of EMT‐associated molecules was measured via western blotting. Results Claudin‐1 expression decreased as TSCC malignancy increased. Adenosine monophosphate–activated protein kinase (AMPK) activation led to increased Claudin‐1 expression and membrane translocation, inhibiting TSCC cell migration and epithelial–mesenchymal transition (EMT). Conversely, Claudin‐1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation. Conclusions Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin‐1 and EMT pathways.

Abstract The Standardized Precipitation Evapotranspiration Index (SPEI) is a widely recognized and effective tool for monitoring meteorological droughts. However, existing SPEI datasets suffer from spatial discontinuity or coarse spatial resolution problems, which limits their applications at the local level for drought monitoring research. Therefore, we calculated the SPEI index at meteorological stations, combined with the Global Precipitation Measurement (GPM) Precipitation (Pre), Moderate Resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST), ERA5‐Land Shortwave Radiation (SR), Shuttle Radar Topography Mission (SRTM) Digital Elevation Model (DEM) datasets and Random Forest Regression (RFR) model, developed a high spatial resolution (1 km) SPEI (HSPEI) datasets with multiple time scales in mainland China from 2001 to 2022. Compared to other SPEI datasets, the HSPEI datasets have higher spatial resolution and can effectively identify the detailed characteristics of drought in mainland China from 2001 to 2022. Overall, the HSPEI datasets can be effectively applied to the research of different droughts in China from 2001 to 2022.

Abstract Maintenance of power transmission lines is essential for the safe and reliable operation of the power grid. The use of deep learning‐based networks to improve the performance of power line defect detection faces significant challenges, such as small target sizes, shape similarities, and occlusion issues. In response to these challenges, a transformer‐based end‐to‐end power line detection network called Power‐DETR is introduced. Initially, building upon Deformable DETR, a large pre‐trained model (Swin‐large) is utilized to increase the number of multi‐scale features, and activation checkpoint technology is applied to ensure effective training within limited memory capacity. Subsequently, a contrastive denoising training strategy is integrated to combat ambiguity and instability of the Hungarian matching algorithm during training, aiming to expedite model convergence. Additionally, a hybrid label assignment strategy combining OHEM and cost‐based ATSS is proposed to provide the model with high‐quality queries, ensuring adequate training for the decoder and enhancing encoder supervision. Experimental results substantiate the efficacy of the proposed Power‐DETR model as a novel end‐to‐end detection paradigm, surpassing both one‐stage and two‐stage detection models. Furthermore, the model demonstrates a significant 15.7% enhancement in mAP0.5 compared to the baseline.

Abstract Underwater sensor networks hold immense potential for advancing the field of underwater target tracking, yet they encounter significant resource constraints stemming from energy storage and communication methods. In order to balance tracking accuracy and energy consumption, the authors present a distributed bearing‐only target tracking algorithm that can be used in underwater sensor networks with resource constraints. Anchored in the diffusion cubature information filter framework, this algorithm achieves fusion for non‐linear bearing measurements and state estimation. During the incremental update stage, individual nodes leverage the Posterior Cramer‐Rao Lower Bound as a metric for tracking performance. Subsequently, a strategy for selecting neighbouring nodes is introduced, ensuring tracking accuracy while efficiently kerbing energy consumption. In the diffusion update stage, a multi‐threshold event triggering mechanism is employed to partially diffuse the intermediate estimation. Additionally, an adaptive convex combination weight is proposed for cases involving partial diffusion. Through theoretical analysis, the asymptotic unbiasedness and convergence of the algorithm have been proven. Through Monte Carlo simulation experiments, the authors verify that the algorithm is superior to existing algorithms. Furthermore, the algorithm significantly reduces energy consumption in information interaction, minimising tracking accuracy loss.

Abstract Binder plays a crucial role in constructing high‐performance electrodes for water electrolysis. While most research has been focused on advancing electrocatalysts, the application of binders in electrode design has yet to be fully explored. Herein, the in situ incorporation of polytetrafluoroethylene (PTFE) as a multifunctional binder, which increases electrochemical active sites, enhances mass transfer, and strengthens the mechanical and chemical robustness of oxygen evolution reaction (OER) electrodes, is reported. The NiFe‐LDH@PTFE/NF electrode prepared by co‐deposition of PTFE with NiFe‐layered double hydroxide onto nickel foam demonstrates exceptional long‐term stability with a minimal potential decay rate of 0.034 mV h−1 at 500 mA cm−2 for 1000 h. The alkaline water electrolyzer utilizing NiFe‐LDH@PTFE/NF requires only 1.584 V at 500 mA cm−2 and sustains high energy efficiency over 1000 h under industrial operating conditions. This work opens a new path for stabilizing active sites to obtain durable electrodes for OER as well as other electrocatalytic systems.

Abstract Migraine exhibits a substantial prevalence worldwide. The current diagnostic criteria rests exclusively on clinical characteristics without any objective and reliable means. The calcitonin gene‐related peptide (CGRP), as a biomarker for distinguishing migraine, undergoes swift degradation, featuring a half‐life of under 10 min, which poses a significant challenge to the point‐of‐care testing of CGRP in clinical application. Here, a photonic crystal (PC)‐based biochip has been developed to detect CGRP via the fluorescence competition assay. The chip integrates the functionalities of fluorescence enhancement and hydrophilic–hydrophobic patterning enrichment, enabling rapid and sensitive detection of CGRP. After investigating the optimal enhancement distance of fluorescence near PCs, the chip allows CGRP detection using

Abstract Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated with the development of a variety of tumors. Combining the GEO database and GBC mRNA‐seq analysis, it is found high expression of the splicing factor polypyrimidine region‐ binding protein 3 (PTBP3) in GBC. Multi‐omics analysis revealed that PTBP3 promoted exon skipping of interleukin‐18 (IL‐18), resulting in the expression of ΔIL‐18, an isoform specifically expressed in tumors. That ΔIL‐18 promotes GBC immune escape by down‐regulating FBXO38 transcription levels in CD8+T cells to reduce PD‐1 ubiquitin‐mediated degradation is revealed. Using a HuPBMC mouse model, the role of PTBP3 and ΔIL‐18 in promoting GBC growth is confirmed, and showed that an antisense oligonucleotide that blocked ΔIL‐18 production displayed anti‐tumor activity. Furthermore, that the H3K36me3 promotes exon skipping of IL‐18 by recruiting PTBP3 via MRG15 is demonstrated, thereby coupling the processes of IL‐18 transcription and alternative splicing. Interestingly, it is also found that the H3K36 methyltransferase SETD2 binds to hnRNPL, thereby interfering with PTBP3 binding to IL‐18 pre‐mRNA. Overall, this study provides new insights into how aberrant alternative splicing mechanisms affect immune escape, and provides potential new perspectives for improving GBC immunotherapy.

Abstract Background Sphingolipids not only serve as structural components for maintaining cell membrane fluidity but also function as bioactive molecules involved in cell signaling and the regulation of various biological processes. Their pivotal role in cancer cell development, encompassing cancer cell proliferation, migration, angiogenesis, and metastasis, has been a focal point for decades. However, the contribution of sphingolipids to the complexity of tumor microenvironment promoting cancer progression has been rarely investigated. Methods Through the integration of publicly available bulk RNA‐seq and single‐cell RNA‐seq data, we conducted a comprehensive analysis to compare the transcriptomic features between tumors and adjacent normal tissues, thus elucidating the intricacies of the tumor microenvironment (TME). Results Disparities in sphingolipid metabolism (SLM)‐associated genes were observed between normal and cancerous tissues, with the TME characterized by the enrichment of sphingolipid signaling in macrophages. Cellular interaction analysis revealed robust communication between macrophages and cancer cells exhibiting low SLM, identifying the crucial ligand‐receptor pair, macrophage inhibitory factor (MIF)‐CD74. Pseudo‐time analysis unveiled the involvement of SLM in modulating macrophage polarization towards either M1 or M2 phenotypes. Categorizing macrophages into six subclusters based on gene expression patterns and function, the SPP1+ cluster, RGS1+ cluster, and CXCL10+ cluster were likely implicated in sphingolipid‐induced M2 macrophage polarization. Additionally, the CXCL10+, AGER+, and FABP4+ clusters were likely to be involved in angiogenesis through their interaction with endothelial cells. Conclusion Based on multiple scRNA‐seq datasets, we propose that a MIF‐targeted strategy could potentially impede the polarization from M1 to M2 and impair tumor angiogenesis in low‐SLM non‐small cell lung cancer (NSCLC), demonstrating its potent antitumor efficacy.

Abstract The Surface Water and Ocean Topography (SWOT) mission provides a good opportunity to study fine‐scale processes in the global ocean but whether it can detect balanced submesoscale eddies is uncertain due to the “contamination” by unbalanced inertial gravity waves. Here, based on concurrent observations from SWOT and a mooring array in the northwestern Pacific, we successfully captured two submesoscale cyclonic eddies with negative sea level anomalies (SLAs) in spring 2023. We find that the SLA amplitude and equivalent radius of the first (second) eddy are 2.5 cm and 16.0 km (2.0 cm and 18.8 km), respectively. For both eddies, their vertical scales are around 150 m and their horizontal velocities and Rossby numbers exceed 15.0 cm/s and 0.4, respectively. Further analysis suggests that similar submesoscale eddies can commonly occur in the northwestern Pacific and that SWOT is capable to detect larger submesoscale eddies with scales greater than ∼10 km.

Abstract Sepsis is an infection‐triggered, rapidly progressive systemic inflammatory syndrome with a high mortality rate. Currently, there are no promising therapeutic strategies for managing this disease in the clinic. Heparanase plays a crucial role in the pathology of sepsis, and its inhibition can significantly relieve related symptoms. Here, a novel heparanase inhibitor CV122 is rationally designed and synthesized, and its therapeutic potential for sepsis with Lipopolysaccharide (LPS) and Cecal Ligation and Puncture (CLP)‐induced sepsis mouse models are evaluated. It is found that CV122 potently inhibits heparanase activity in vitro, protects cell surface glycocalyx structure, and reduces the expression of adhesion molecules. In vivo, CV122 significantly reduces the systemic levels of proinflammatory cytokines, prevents organ damage, improves vitality, and efficiently protects mice from sepsis‐induced death. Mechanistically, CV122 inhibits the activity of heparanase, reduces its expression in the lungs, and protects glycocalyx structure of lung tissue. It is also found that CV122 provides effective protection from organ damage and death caused by Crimean‐Congo hemorrhagic fever virus (CCHFV) infection. These results suggest that CV122 is a potential drug candidate for sepsis therapy targeting heparanase by inhibiting cytokine storm.

Abstract The one‐stage object detector has been widely applied in many computer vision applications due to its high detection efficiency and simple framework. However, one‐stage detectors heavily rely on Non‐maximum Suppression to remove the duplicated predictions for the same objects, and the detectors produce detection confidence to measure the quality of those predictions. The localisation quality is an important factor to evaluate the predicted bounding boxes, but its role has not been fully utilised in previous works. To alleviate the problem, the Quality Prediction Block (QPB), a lightweight sub‐network, is designed by the authors, which strengthens the effect of localisation quality evaluation on detection confidence by leveraging the features of predicted bounding boxes. The QPB is simple in structure and applies to different forms of detection confidence. Extensive experiments are conducted on the public benchmarks, MS COCO, PASCAL VOC and Berkeley DeepDrive. The results demonstrate the effectiveness of our method in the detectors with various forms of detection confidence. The proposed approach also achieves better performance in the stronger one‐stage detectors.

Abstract New therapeutic targets and drugs are urgently needed to halt the fibrosing process in idiopathic pulmonary fibrosis (IPF). SHR‐1906 is a novel fully humanized monoclonal antibody against the connective tissue growth factor, which plays an essential role in the genesis of IPF. We assessed the safety, tolerability, pharmacokinetics (PKs), and immunogenicity of single dose SHR‐1906 in healthy participants. This was a randomized, double‐blind, placebo‐controlled, dose‐escalation, phase I study. Twelve healthy participants for each dose level were enrolled to receive single ascending doses of SHR‐1906 intravenously (1.5, 6, 12, 20, 30, and 45 mg/kg) or placebo and followed for 71 days. The primary end points were safety and tolerability. Treatment‐related treatment‐emergent adverse events occurred in 25 participants (46.3%) in the SHR‐1906 group and 11 (61.1%) in the placebo group. No serious adverse events occurred. Over the dose range investigated, the geometric mean clearance was 0.14–0.63 mL/h/kg, the geometric mean volume of distribution at steady‐state was 47.4–75.5 mL/kg, and the terminal elimination half‐life was 51.9–349 h. SHR‐1906 showed nonlinear PKs. The peak concentration increased in a dose‐proportional manner, whereas the area under the concentration–time curve showed a greater than dose‐proportional increase. Anti‐drug antibodies of SHR‐1906 were detected in nine of 54 participants (16.7%). A single dose of SHR‐1906 up to 45 mg/kg demonstrated a favorable tolerability profile in healthy participants. The PKs and immunogenicity of SHR‐1906 were evaluated, supporting further clinical development.

Abstract Earthworms, long utilized in traditional medicine, serve as a source of inspiration for modern therapeutics. Lysenin, a defensive factor in the coelom fluid of the earthworm Eisenia fetida, has multiple bioactivities. However, the inherent toxicity of Lysenin as a pore‐forming protein (PFP) restricts its application in therapy. Here, a gene therapy strategy based on Lysenin for cancer treatment is presented. The formulation consists of polymeric nanoparticles complexed with the plasmid encoding Lysenin. After transfection in vitro, melanoma cells can express Lysenin, resulting in necrosis, autophagy, and immunogenic cell death. The secretory signal peptide alters the intracellular distribution of the expressed product of Lysenin, thereby potentiating its anticancer efficacy. The intratumor injection of Lysenin gene formulation can efficiently kill the transfected melanoma cells and activate the antitumor immune response. Notably, no obvious systemic toxicity is observed during the treatment. Non‐viral gene therapy based on Lysenin derived from Eisenia foetida exhibits potential in cancer therapy, which can inspire future cancer therapeutics.

Abstract Objective To explore the role of miRNA in liver damage caused by Echinococcus multilocularis infection. Methods Six female C57BL mice were randomly divided into two groups, the control group and the infection group. Mice in the control group were injected with 100 μL PBS through the hepatic portal vein, and mice in the infection group were infected with E. multilocularis via the hepatic portal vein to establish a mouse model of infection. Small RNA sequencing was performed for detecting the expression of miRNAs in the liver of mice infected with 2000 E. multilocularis after 3 months of infection, screen out miRNAs related to liver damage, and verify by RT‐PCR. Results Seventy‐one differentially expressed miRNAs were found in the liver in comparison with control, and a total of 36 mouse miRNAs with |FC| >0.585 were screened out, respectively. In addition, Targetscan (V5.0) and miRanda (v3.3a) software were used to predict differential miRNAs target genes and functional enrichment of target genes. Functional annotation showed that “cytokine‐cytokine interaction,” “positive regulation of cytokine production,” “inflammatory response,” and “leukocyte activation” were enriched in the liver of E. multilocularis‐infected mice. Moreover, the pathways “human cytomegalovirus infection,” “cysteine and methionine metabolism,” “Notch signaling pathway,” and “ferroptosis” were involved in liver disease. Furthermore, four miRNAs (mmu‐miR‐30e‐3p, mmu‐miR‐203‐3p, mmu‐miR‐125b‐5p, and mmu‐miR‐30c‐2‐3p) related to liver injury were screened and verified. Conclusion This study revealed that the expression profiling of miRNAs in the livers was changed after E. multilocularis infection, and improved our understanding of the transcriptomic landscape of hepatic echinococcosis in mice.

Abstract Background Cancer threat is relevant to age, and the threat of a foreshortened life coupled with a lengthy treatment process negatively affects middle‐aged and older adults. Understanding the coping throughout the cancer experience in middle‐aged and older cancer survivors will help develop supportive care to promote their physiological and psychological coping effects. Objectives To explore the cancer coping experiences of middle‐aged adults aged 40–59 and older adults over 60. Design A descriptive phenomenological study was employed. Methods Face‐to‐face, in‐depth, semistructured interviews were conducted with 22 oncology patients in a tertiary university hospital aged 40 or above from August to October 2023. The interview data were analyzed using thematic analysis procedures. Results Five themes and 13 subthemes were formed through analysis: acceptance of cancer (considering cancer as chronic, believing in fate and attributing cancer to karma); having different information needs (desired to be truthfully informed, information‐seeking behaviour, information avoidance behaviour); getting families involved (developing dependent behaviours, feeling emotional support, family members suffering worse); striving to maintain positive psychological state (positive thinking, seeking peer support) and negative experience (undesirable, low self‐esteem). Conclusion Our study reveals that cancer survivors' attitudes towards having cancer have changed from a death sentence to a more positive perception of a chronic disease. Supportive programmes for developing coping strategies should consider the cultural traditions and religious beliefs, different information needs, involvement of family and promoting a positive psychological state while avoiding negative factors. Patient or Public Contribution Participants with experience of coping with cancer were involved in the semistructured interview.

Abstract Gravity‐induced drainage is one of the main destabilizing mechanisms for soap bubbles and foams. Here we show that solely through acoustic levitation without introducing any chemical stabilizers, liquid drainage in the bubble film can be completely inhibited, therefore leading to a significant enhancement of bubble lifetime by more than two orders of magnitude and enabling the bubble to survive puncturing by a needle. Based on sound simulation and force analysis, it has been found that acoustic radiation force, exerted on both the inner and outer surfaces of the levitated bubble, acts in opposite directions, thus providing a squeezing effect to the bubble film. The hydrostatic pressure that induces drainage has been balanced by the acoustic radiation pressure exerted on both sides of the film, which is at the origin of the sound stabilization mechanism. This study provides new insights into the interplay between sound and soap bubbles or films, thus stimulating a wide range of fundamental research concerning bubble films and expanding their applications in bio/chemical reactors.

Abstract To improve the development efficiency of ultradeep fault‐controlled carbonate reservoirs, the deformation and connectivity mechanism of fractures was revealed through large‐scale rock mechanical experiments. The in situ stress field and fracture activity distribution law of fault‐control carbonate reservoirs were clarified through geomechanical modeling. It is revealed that the fracture activity in different directions and the connectivity of the fracture and cavity in different parts are significantly different, the development effect of different well trajectories is analyzed, and the integrated working method of geological engineering is proposed to scientifically guide the well trajectory design and water injection scheme optimization. The results show that: (1) Large‐scale fractures and high‐angle fracture systems in the deformation of strike–slip faults are the key factors affecting reservoir quality. High‐pressure water injection can activate preexisting fractures, and it can extend on the basis of preexisting fractures, and even generate new fractures, which promote the interconnection of fault‐controlled fracture‐cave bodies in the vertical and horizontal directions. (2) During the process of high‐pressure water injection, the coupling change between mechanics and flow occurs inside the fracture body, the seepage environment is improved, and the oil and gas recovery factor is improved through cyclic lifting. (3) According to the shape and occurrence of the fault body and the dynamic shear deformation connectivity of the fault surface, the best well point and well trajectory of the directional well can be optimized, and the water injection scheme can be optimized. (4) The single‐well production increased by 1.45 × 104 t through high‐pressure water injection, the cumulative oil increase of the same fracture‐cavity body increased by 4.63 × 104 t. This method is highly efficient for ultradeep fault‐controlled oil reservoirs. The development provides a good theoretical basis and technical support, and plays a leading and exemplary role.

Abstract Crosstalk between tumors and the nervous system has emerged as a significant hallmark of human cancer. In the central nervous system, neurons closely interact with tumor cells, promoting the proliferation of glioma and neuroblastoma. Additionally, the peripheral nervous system plays a crucial role in reshaping the tumor microenvironment, modulating angiogenesis, and regulating immune cell function, while also directly promoting tumorigenesis and metastasis. Current research has elucidated some of the specific neural signaling mechanisms involved in this crosstalk, including neurotransmitters, neuropeptides, and growth factors. In this review, we aim to summarize these mechanisms and highlight the latest discoveries in various solid tumors, such as glioma, pancreatic, prostate, and gastrointestinal cancers. By understanding the intricate crosstalk between cancer cells and the nervous system, we can develop more effective and targeted treatments for cancer patients.

Abstract In this paper, an improved two‐step method is presented for the sensitivity analysis of vector network analyzer (VNA) S‐parameter measurements due to the non‐ideal line‐reflect‐match (LRM) calibration standards. This improved method is based on the indirect uncertainty propagation mechanism, which is especially suitable for the S‐parameter measurements applying the self‐calibration technique. To further simplify the formula derivation, the deviation matrices [δA] and [δB] are newly defined to represent the uncertainties of the T‐matrices of error boxes. With this definition, formulas for the deviations of device under test (DUT) S‐parameters can be concluded as functions of [δA] and [δB] in a concise form. Eventually, by solving only three linear combinations of the elements from [δA] and [δB], the sensitivity coefficients of DUT S‐parameters due to non‐ideal LRM can be conveniently deduced in an analytical form. Finally, experiments are performed to verify the proposed method.

Abstract Background The association between adrenal size and metabolic profiles in patients with diabetes mellitus (DM) is unclear. This study was conducted to determine whether the adrenal thickness measured by computed tomography (CT) is correlated with the metabolic profiles of patients with DM. Methods This was a cross‐sectional study including 588 Chinese hospitalized patients with DM without comorbidities or medications known to affect adrenal morphology or hormone secretion. Adrenal limb thickness was measured on unenhanced chest CT. Participants were stratified into tertiles according to their total adrenal limb thickness. Linear and logistic regression models were used to estimate the correlations. Results After adjustment for sex and age, the adrenal thickness was positively associated with body mass index (BMI), waist circumference (WC), urinary albumin/creatinine ratio, and 24‐h urinary free cortisol (UFC) and negatively correlated with high‐density lipoprotein cholesterol. The sequential equation model (SEM) suggested UFC partially mediated the effect of adrenal limb thickness on WC by 12%. Adrenal thickness, but not UFC, was associated with a higher risk of existing hypertension (odds ratio [OR] = 3.78, 95% confidence interval [CI] 1.58, 9.02) and hyperlipidemia (OR = 2.76, 95% CI 1.03, 7.38), independent of age, gender, BMI, and WC. Conclusions The adrenal thickness is independently associated with BMI, WC, cortisol levels, urinary albumin/creatinine ratio, hypertension, and dyslipidemia but not glycemic parameters in patients with diabetes. Our study encourages further studies to investigate the role of adrenal physiology in patients with diabetes.

Abstract The plant hormone salicylic acid (SA) plays critical roles in plant innate immunity. Several SA derivatives and associated modification are identified, whereas the range and modes of action of SA‐related metabolites remain elusive. Here, the study discovered 2,4‐dihydroxybenzoic acid (2,4‐DHBA) and its glycosylated form as native SA derivatives in plants whose accumulation is largely induced by SA application and Ps. camelliae‐sinensis (Pcs) infection. CsSH1, a 4/5‐hydroxylase, catalyzes the hydroxylation of SA to 2,4‐DHBA, and UDP‐glucosyltransferase UGT95B17 catalyzes the formation of 2,4‐DHBA glucoside. Down‐regulation reduced the accumulation of 2,4‐DHBA glucosides and enhanced the sensitivity of tea plants to Pcs. Conversely, overexpression of UGT95B17 increased plant disease resistance. The exogenous application of 2,4‐DHBA and 2,5‐DHBA, as well as the accumulation of DHBA and plant resistance comparison, indicate that 2,4‐DHBA functions as a potentially bioactive molecule and is stored mainly as a glucose conjugate in tea plants, differs from the mechanism described in Arabidopsis. When 2,4‐DHBA is applied exogenously, UGT95B17‐silenced tea plants accumulated more 2,4‐DHBA than SA and showed induced resistance to Pcs infection. These results indicate that 2,4‐DHBA glucosylation positively regulates disease resistance and highlight the role of 2,4‐DHBA as potentially bioactive molecule in the establishment of basal resistance in tea plants.

Abstract Neuroinflammation is associated with poor outcomes in patients with spinal cord injury (SCI). Recent studies have demonstrated that stimulator of interferon genes (Sting) plays a key role in inflammatory diseases. However, the role of Sting in SCI remains unclear. In the present study, it is found that increased Sting expression is mainly derived from activated microglia after SCI. Interestingly, knockout of Sting in microglia can improve the recovery of neurological function after SCI. Microglial Sting knockout restrains the polarization of microglia toward the M1 phenotype and alleviates neuronal death. Furthermore, it is found that the downregulation of mitofusin 2 (Mfn2) expression in microglial cells leads to an imbalance in mitochondrial fusion and division, inducing the release of mitochondrial DNA (mtDNA), which mediates the activation of the cGas‐Sting signaling pathway and aggravates inflammatory response damage after SCI. A biomimetic microglial nanoparticle strategy to deliver MASM7 (named MSNs‐MASM7@MI) is established. In vitro, MSNs‐MASM7@MI showed no biological toxicity and effectively delivered MASM7. In vivo, MSNs‐MASM7@MI improves nerve function after SCI. The study provides evidence that cGas‐Sting signaling senses Mfn2‐dependent mtDNA release and that its activation may play a key role in SCI. These findings provide new perspectives and potential therapeutic targets for SCI treatment.

Abstract Advanced sustainable biomedical materials are urgently needed for clinical applications; however, developing biomedical materials with exceptional mechanical and bactericidal properties as well as removable functionalities to reduce unintended secondary injury remains a challenge. Here, we report a biomass‐derived composite consisting of water‐soluble fish gelatin (FG) and antibacterial ZnO@silk fibroin (ZSF) microspheres for potential application as the wound dressing. The ZSF microspheres are embedded in a FG matrix to realize the stretchable, antibacterial, and removable ZSF/FG composites. By introducing glycerin as the plasticizer, ZSF/FG composites deliver a tensile strength of 4.5 MPa and stretchability of 550%. Acting as both the germicide and hydrophile components, ZSF microspheres endow the composites with excellent antibacterial capacity and water solubility. To prevent secondary injury, the ZSF/FG composites can be easily removed from the wounds by simply exposing them to excess water. Additionally, the ZSF/FG composites exhibit favorable biocompatibility and sustain high cell viability of over 100%. The full‐thickness skin wound model on infected mice demonstrated an efficient rate of wound closure and a reduced inflammatory response. The ZSF/FG composite shows promise to hasten the healing of infected wounds and is expected a promising candidate as wound dressing for clinical therapy.

Abstract Background Giant cell tumor of the bone (GCTB), an intermediate locally aggressive neoplasm that frequently involves the epiphyseal region of the long bones. GCTB of the distal phalanx and soft‐tissue recurrences are extremely rare. Little is known about the cellular and molecular differences between GCTB of the long bones and rare sites. Methods We employed single‐cell RNA sequencing to elucidate the transcriptional profiles of 28,992 cells originating from patients afflicted with GCTB in the femur, distal phalanx, and soft‐tissue relapse. To confirm the critical findings, we subjected the paraffin sections of GCTB to immunohistochemical staining. Results Our study revealed that GCTBs in rare sites display distinct immune subtypes and antigen presentation gene signatures. We observed minimal lymphocyte infiltration in GCTBs of the phalanx. Further analyses demonstrated that the transforming growth factor‐β pathway and profibrotic proteins were significantly upregulated in phalanx lesions. In contrast, GCTB cells from soft‐tissue recurrence exhibited discernible chondrocyte characteristics but presented lower antigen‐presenting ability compared to those from femur lesions. Notably, we identified an immunosuppressive subset of mast cells in the soft‐tissue recurrence. The secretion of proangiogenic and immunosuppressive factors from these mast cells suggests their potential role in the formation of vascular‐rich and immunosuppressive niches in recurrent lesions. Conclusions Collectively, this study broadens our comprehension of the gene expression patterns observed in infrequent location GCTBs and furnishes a repository of information for illuminating promising therapeutic targets for rare GCTBs.

Abstract Objective Cystic echinococcosis (CE), a zoonotic parasitic disease caused by Echinococcus granulosus, remains a public health and socioeconomic issue worldwide, making its prevention and treatment of vital importance. The aim of this study was to investigate changes in the intestinal microbiota of mice immunized with three peptide vaccines based on the recombinant antigen of E. granulosus, P29 (rEg.P29), with the hope of providing more valuable information for the development of vaccines against CE. Methods Three peptide vaccines, rEg.P29T, rEg.P29B, and rEg.P29T + B, were prepared based on rEg.P29, and a subcutaneous immunization model was established. The intestinal floras of mice in the different immunization groups were analyzed by 16 S rRNA gene sequencing. Results The intestinal microbiota analysis at both immunization time points revealed that Firmicutes, Bacteroidota, and Verrucomicrobiota were the predominant flora at the phylum level, while at the genus level, Akkermansia, unclassified_Muribaculaceae, Lachnospiraceae_NK4A136_group, and uncultured_rumen bacterium were the dominant genera. Some probiotics in the intestines of mice were significantly increased after immunization with the peptide vaccines, such as Lactobacillus_taiwanensis, Lactobacillus_reuteri, Lachnospiraceae_NK4A136_group, Bacteroides_acidifaciens, and so forth. Meanwhile, some harmful or conditionally pathogenic bacteria were decreased, such as Turicibacter sanguinis, Desulfovibrio_fairfieldensis, Clostridium_sp, and so forth, most of which are associated with inflammatory or infectious diseases. Kyoto Encyclopaedia of Genes and Genomes enrichment analysis revealed that the differential flora were enriched in multiple metabolic pathways, primarily biological systems, human diseases, metabolism, cellular processes, and environmental information processing. Conclusion In this study, we comprehensively analyzed and compared changes in the intestinal microbiota of mice immunized with three peptide vaccines as well as their related metabolic pathways, providing a theoretical background for the development of novel vaccines against E. granulosus.

Abstract Objective Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infectious disease in children. The study aimed to elucidate the therapeutic efficacy of aerosolized budesonide and N‐acetylcysteine combination therapy for MP infection in children. Methods One hundred and twenty children with MP infection were included and divided into the control group (received aerosol inhalation of budesonide) and the experimental group (aerosolized budesonide and N‐acetylcysteine). After treatment, the disappearance time of clinical symptoms and efficacy were contrasted between the two groups. Results With the passage of treatment time, the children's cough score of the two groups were gradually reduced. The children in the experimental group got well from the cough faster than the control group, and the difference reached a significant level on the 5th and 7th days. The time required for fever, rale, and cough to disappear in the experimental group was shorter than those in the control group. As the treatment progressed, a gradual decrease in serum interleukin‐6, tumor necrosis factor‐α, and C‐reactive protein values was detected in both groups, and the decrease was more significant in the experimental group. The total effective rate of the experimental group was 98.33%, which surpassed the control group (93.33%). Conclusion Budesonide and N‐acetylcysteine combination therapy in the treatment of MP infection in children has a significant effect, and can quickly relieve the clinical symptoms of children with good safety. It is worthy of widespread clinical use.

Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods and Results We performed cross‐sectional and prospective association analyses of blood‐derived mtDNA CN and cardiovascular disease outcomes in 27 316 participants in 8 cohorts of multiple racial and ethnic groups with whole‐genome sequencing. We also performed Mendelian randomization to explore causal relationships of mtDNA CN with coronary heart disease (CHD) and cardiometabolic risk factors (obesity, diabetes, hypertension, and hyperlipidemia). P

Abstract A significant portion (∼2.1 Sv, 1 Sv = 106 m3 s−1) of deep water penetrates into the Philippine Sea through the Yap‐Mariana Junction, the sole passage of the Philippine Sea below 4,000 m, and is then upwelled into shallower layers, closing regional overturning circulation. Yet, the structure and variability of this diapycnal upwelling remain poorly understood. Here, we report on a fine‐resolution hydrographic observation conducted at the most significant topographic feature in the Philippine Sea, the Kyushu‐Palau Ridge (KPR). Enhanced mixing up to O(10−2) m2 s−1 near the KPR is manifested, indicating the presence of substantial upwelling herein. Besides, the ridge‐related topography contributes more deep‐water mass transformation than abyssal basins in the Philippine Sea. This study highlights the significant role of rough bathymetry features in generating diapycnal upwelling in the North Pacific.

Abstract Background Preeclampsia (PE) is a pregnancy related disease that affects about 5% of pregnancies. Death receptor 3 (DR3) expression is significantly elevated in both placental tissue and plasma of PE patients. However, whether DR3 was involved in trophoblasts in pathogenesis of PE are not well elucidated. Objective Our research was designed to illustrate the biological roles of DR3 in placental trophoblasts, as well as explain its relevant mechanisms. Methods HTR‐8/SVneo cells viability, migration, invasion, and apoptosis were assessed using MTT, Transwell assay, and flow cytometry analysis, respectively. Levels of DR3, PI3K, and AKT in HTR‐8/SVneo cells were analyzed via reverse transcription‐quantitative polymerase chain reaction assay. Western blot analysis was utilized to assess DR3, p‐PI3K, p‐AKT, PI3K, and AKT protein expression. Results Upregulation of DR3 obviously inhibited HTR‐8/SVneo cells viability, migration, and invasion, as well as promoted HTR‐8/SVneo cells apoptosis, as opposed to the control‐plasmid group. We also found that DR3‐plasmid enhanced cleaved‐caspase3 expression, reduced p‐PI3K and p‐AKT protein expression, and p‐PI3K/PI3K or p‐AKT/AKT ratio in HTR‐8/SVneo cells. Importantly, IGF‐1, a PI3K/AKT signaling pathway agonist, partially reversed the effects of DR3‐plasmid on the cell viability, migration, invasion, apoptosis, and PI3K/AKT signal pathway in HTR‐8/SVneo cells. Conclusion DR3 was involved in PE through regulating placental trophoblast cell physiology via PI3K/AKT pathway, which might be a promising therapeutic target for PE therapy.

Abstract Objectives To explore the diagnostic value of radiomics in differentiating between lung adenocarcinomas appearing as ground‐glass opacity nodules (GGO) with high‐ and low Ki‐67 expression levels. Materials and Methods From January 2018 to January 2021, patients with pulmonary GGO who received lung resection were evaluated for potential enrollment. The included GGOs were then randomly divided into a training cohort and a validation cohort with a ratio of 7:3. Logistic regression (LR), decision tree (DT), support vector machines (SVM), and adaboost (AB) were applied for radiomic model construction. Area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of the established models. Results Seven hundred and sixty‐nine patients with 769 GGOs were included in this study. Two hundred and forty‐five GGOs were confirmed to be of high Ki‐67 labeling index (LI). In the training cohort, gender, age, spiculation sign, pleural indentation sign, bubble sign, and maximum 2D diameter of the nodule were found to be significantly different between high‐ and low Ki‐67 LI groups (p

Abstract Aims The optimal treatment for severe aortic valve disease complicated with moderate function mitral regurgitation (FMR) remains controversial. Although isolated surgical aortic valve replacement (SAVR) is reasonable, previous studies also show that moderate FMR might deteriorate after surgical treatment and result in poorer prognosis. Because the left ventricular remodelling plays a critical role in the development of FMR, these patients might potentially benefit from the administration of β‐blocker (BB). Unfortunately, relevant clinical evidence is lacking. This study aimed to investigate the impact of post‐operative administration of BB on the outcomes of moderate FMR patients undergoing isolated SAVR. Methods In this single‐centre cohort study, patients who underwent isolated SAVR and complicated with pre‐operative moderate FMR during 2010 and 2019 at our centre were retrospectively recruited. Patients were divided into two groups according to postoperative administration of BB (BB group vs. control group). The cumulative survival rates were calculated using the Kaplan–Meier method and tested by the log‐rank test, followed by inverse probability treatment weighting (IPTW) analysis to further control the between‐group imbalances. The primary outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), a composite endpoint of all‐cause death, repeat heart valve surgery, non‐fatal myocardial infarction, stroke, and hospitalization for heart failure. Results A total of 165 patients were enrolled, 57 (34.6%) of whom were female, and the mean age was 59.2 ± 12.2 years. Eighty (48.5%) patients received post‐operative BB therapy. The median follow‐up time was 18.4 months. The administration of BB was not associated with lower risk of MACCE [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.29–1.62, P = 0.388] or all‐cause death (HR: 1.03, 95% CI: 0.30–0.56, P = 0.967). In the IPTW dataset, the total number of patients were 326.89, and the outcomes regarding the risk of MACCE (HR: 0.79, 95% CI: 0.31–1.97, P = 0.607) and all‐cause death (HR: 1.33, 95% CI:0.35–5.05, P = 0.674) were in line with the unmatched analysis. The follow‐up echocardiographic results were available for 72.2% of the overall cohort, and the use of BB was observed to be associated with higher improvement rate of follow‐up FMR according to the IPTW analysis (92.2% vs. 98.3%, P = 0.033). Conclusions The administration of BB after SAVR was not associated with lower risk of MACCE for patients of severe aortic valve disease complicated with moderate FMR, but was potentially beneficial for improving FMR.

Objective A detailed analysis of the morphology of distal humeral articulation can help in the creation of anatomic prostheses of hemiarthroplasty. This study used statistical shape modeling to evaluate the 3D morphology of the distal humerus in healthy Chinese individuals and to investigate the proper articular morphology differences. Methods A statistical shape model (SSM) of the distal humerus was created using CT scans of 106 survey‐confirmed nonpathologic elbows. In addition, the articular components of each principal component (PC) were selected and fitted on the mean mode. The Euclidean point‐to‐mesh distance of articular modes was calculated as a measurement the proper change in the morphology of the articulation. Results The first seven PCs jointly accounted for 80.9% of the total variation (44.4%, 12.2%, 7.9%, 5.9%, 4.1%, 3.4% and 3%, respectively). In the mean model, the distance between the medial and lateral epicondyles was 57.4 mm, the width of the articulation was 42.1 mm, and the angle of the transepicondylar line (TEL) and C line was 4.8°. The articular surface differences of the first PC were significant (RMS: 1.43 mm in the −3 SD model and 2.38 mm in the +3 SD model), whereas under other conditions, the differences were not remarkable despite the maximum deformation not exceeding 1 mm. Conclusion A novel method (SSM) was used to evaluate the 3D morphology of the distal humerus in healthy Chinese individuals and investigate the proper articular shape differences. We found the proper shape of articular surface basically transformed into one variation pattern which was relevant to the bone size, even though the morphology of distal humerus possessed complicated variation modes. The findings of this study can be helpful to design the next generation of elbow hemiarthroplasty in the future.

Abstract Designing and synthesizing advanced electrocatalysts with superior intrinsic activity toward hydrogen evolution reaction (HER) in alkaline media is critical for the hydrogen economy. Herein, a novel Ir@Rhene heterojunction electrocatalyst is synthesized via epitaxially confining ultrasmall and low‐coordinate Ir nanoclusters on the ultrathin Rh metallene accompanying the formation of Ir/IrO2 Janus nanoparticles. The as‐prepared heterojunctions display outstanding alkaline HER activity, with an overpotential of only 17 mV at 10 mA cm−2 and an ultralow Tafel slope of 14.7 mV dec−1. Both structural characterizations and theoretical calculations demonstrate that the Ir@Rhene heterointerfaces induce charge density redistribution, resulting in the increment of the electron density around the O atoms in the IrO2 site and thus delivering much lower water dissociation energy. In addition, the dual‐site synergetic effects between IrO2 and Ir/Rh interface trigger and improve the interfacial hydrogen spillover, thereby subtly avoiding the steric blocking of the active site and eventually accelerating the alkaline HER kinetics.

Abstract Bubbles in air are ephemeral because of gravity‐induced drainage and liquid evaporation, which severely limits their applications, especially as intriguing bio/chemical reactors. In this work, a new approach using acoustic levitation combined with controlled liquid compensation to stabilize bubbles is proposed. Due to the suppression of drainage by sound field and prevention of capillary waves by liquid compensation, the bubbles can remain stable and intact permanently. It has been found that the acoustically levitated bubble shows a significantly enhanced particle adsorption ability because of the oscillation of the bubble and the presence of internal acoustic streaming. The results shed light on the development of novel air‐purification techniques without consuming any solid filters.

Abstract Converting building and environment heat into electricity is a promising strategy for energy harvest to tackle global energy and environmental problems. The processing challenges, mechanical brittleness, and low environmental tolerance of typical thermoelectric materials, however, prevent them from realizing their full potential when employed in outdoor building systems. Herein, a general concept based on synergistic ionic associations to significantly improve the mechanical properties and harsh environment stability for high‐performance ionic‐type thermoelectric (i‐TE) gels is explored. They demonstrate extraordinarily high stretchability (1300–2100%), fast self‐healing (120 s), temperature insensitivity, and great water‐proof performance, and could be painted on a variety of surfaces. The n‐type ionic Seebeck coefficient is up to −8.8 mV K−1 and the ionic conductivity is more than 0.14 mS cm−1. Both exhibit remarkable thermal and humidity stability (293–333 K, 20–100 RH%), which are rarely achieved in previous studies. Even on a cloudy day, the open‐circuit thermovoltage for a painted i‐TE array with an area of about 8.5 × 10−3 m2 is above 2 V. This research offers a promising approach for gathering significant waste heat and even solar energy on outside building surfaces in an effective and sustainable manner.

Abstract Introduction Epilepsy is one of the most common and serious brain syndromes and has adverse consequences on a patient's neurobiological, cognitive, psychological, and social wellbeing, thereby threatening their quality of life. Some patients with epilepsy experience poor treatment effects due to the unclear pathophysiological mechanisms of the syndrome. Dysregulation of the mammalian target of the rapamycin (mTOR) pathway is thought to play an important role in the onset and progression of some epilepsies. Methods This review summarizes the role of the mTOR signaling pathway in the pathogenesis of epilepsy and the prospects for the use of mTOR inhibitors. Results The mTOR pathway functions as a vital mediator in epilepsy development through diverse mechanisms, indicating that the it has great potential as an effective target for epilepsy therapy. The excessive activation of mTOR signaling pathway leads to structural changes in neurons, inhibits autophagy, exacerbates neuron damage, affects mossy fiber sprouting, enhances neuronal excitability, increases neuroinflammation, and is closely associated with tau upregulation in epilepsy. A growing number of studies have demonstrated that mTOR inhibitors exhibit significant antiepileptic effects in both clinical applications and animal models. Specifically, rapamycin, a specific inhibitor of TOR, reduces the intensity and frequency of seizures. Clinical studies in patients with tuberous sclerosis complex have shown that rapamycin has the function of reducing seizures and improving this disease. Everolimus, a chemically modified derivative of rapamycin, has been approved as an added treatment to other antiepileptic medicines. Further explorations are needed to evaluate the therapeutic efficacy and application value of mTOR inhibitors in epilepsy. Conclusions Targeting the mTOR signaling pathway provides a promising prospect for the treatment of epilepsy.

Abstract Objectives Neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII), easily accessible systemic inflammation response parameters, were reported to associate with poor lung cancer prognosis. However, research on the effects of these markers on the risk of positive nodules (PNs) and lung cancer is limited. Methods Participants in this retrospective study were those who had their first computed tomography (CT) screening at Jiangsu Province Hospital's Health Promotion Center between January 1, 2017 and December 31, 2020. We identified PNs (≥6 mm in diameter) from free text of CT reports and lung cancer from medical records. Multivariate logistic analysis was used to assess the association between NLR, PLR, or SII and PNs or lung cancer. Results The detected rate of PNs was 9.60% among the 96,476 participants. Age, smoking and body mass index were possible influencing factors for PNs. We observed linear dose‐effect relationship between NLR, PLR, or SII and PNs (pnon‐linear > 0.05). Compared with low quintile, participants with top quintiles of NLR, PLR or SII had an increased risk of PNs, with the adjusted ORs of 1.19 (1.11–1.28), 1.11 (1.04–1.19) or 1.11 (1.03–1.18), respectively. Meanwhile, NLR showed the U‐shaped relationship with lung cancer, with adjusted ORs of 1.40 (1.08–1.81) comparing highest NLR quintile to the third quintile. The high PLR and SII showed significantly associated with lung cancer with adjusted ORs of 1.29 (0.99–1.68) and 1.35 (1.04–1.74) comparing to the lowest quintile. Conclusions The high levels of systemic inflammation markers were associated with the risk of positive pulmonary nodules and lung cancer, which suggested systemic immune response may be an important pre‐clinical feature for the early identification of diseases.

Summary The metabolic flux of fatty acyl‐CoAs determines lipopeptide biosynthesis efficiency, because acyl donor competition often occurs from polyketide biosynthesis and homologous pathways. We used A40926B0 as a model to investigate this mechanism. The lipopeptide A40926B0 with a fatty acyl group is the active precursor of dalbavancin, which is considered as a new lipoglycopeptide antibiotic. The biosynthetic pathway of fatty acyl‐CoAs in the A40926B0 producer Nonomuraea gerenzanensis L70 was efficiently engineered using endogenous replicon CRISPR (erCRISPR). A polyketide pathway and straight‐chain fatty acid biosynthesis were identified as major competitors in the malonyl‐CoA pool. Therefore, we modified both pathways to concentrate acyl donors for the production of the desired compound. Combined with multiple engineering approaches, including blockage of an acetylation side reaction, overexpression of acetyl‐CoA carboxylase, duplication of the dbv gene cluster and optimization of the fermentation parameters, the final strain produced 702.4 mg l‐1 of A40926B0, a 2.66‐fold increase, and the ratio was increased from 36.2% to 81.5%. Additionally, an efficient erCRISPR‐Cas9 editing system based on an endogenous replicon was specifically developed for L70, which increased conjugation efficiency by 660% and gene‐editing efficiency was up to 90%. Our strategy of redirecting acyl donor metabolic flux can be widely adopted for the metabolic engineering of lipopeptide biosynthesis.

Abstract High‐grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single‐cell RNA sequencing (scRNA‐Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA‐Seq is used to identify a unique initiating cell subpopulation (SULT1E1+) in high‐grade meningiomas. This subpopulation modulates the polarization of M2‐type macrophages and promotes meningioma progression and recurrence. A novel patient‐derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1+ and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1+ in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high‐grade meningiomas and provide a novel therapeutic target for refractory high‐grade meningioma.

Precise control over flow rate and flow pattern is critical for investigating the contribution of shear force in cellular responses, biofluidic transport, and living matter in a flowing environment. Generation and control over the ultralow flow fields at microscale are, however, difficult, due to thermal agitation and fluctuations in the surrounding environment. Herein, pa novel microfluidic flow field generator is proposed, capable of generating stable flow field down to the limit of thermal noise. Integrated with a customized MATLAB program controlling timely open–close of 18 monolithic PDMS valves, the flow generator outperforms the existing methods by both achievable low flow rate, that is, 0.01 nL s−1, temporal resolution of flow rate fluctuation down to 100 ms, and provides complex flow patterns. Moreover, unlike external devices (e.g., the syringe pump), the design can be easily integrated into any fluidic chip and sealed from the disturbance of experimental conditions, for example, the airflow and the movement of connected pipelines. The methodology is, therefore, suitable for biological and biophysical studies requiring a well‐defined flowing environment.

Abstract Immunotherapy is an attractive treatment strategy for cancer, while its efficiency and safety need to be improved. A dual‐cascade activatable nanopotentiator for sonodynamic therapy (SDT) and chemodynamic therapy (CDT)‐cooperated immunotherapy of deep tumors via reshaping adenosine metabolism is herein reported. This nanopotentiator (NPMCA) is constructed through crosslinking adenosine deaminase (ADA) with chlorin e6 (Ce6)‐conjugated manganese dioxide (MnO2) nanoparticles via a reactive oxygen species (ROS)‐cleavable linker. In the tumor microenvironment with ultrasound (US) irradiation, NPMCA mediates CDT and SDT concurrently in deep tumors covered with 2‐cm tissues to produce abundant ROS, which results in dual‐cascade scissoring of ROS‐cleavable linkers to activate ADA within NCMCA to block adenosine metabolism. Moreover, immunogenic cell death (ICD) of dying tumor cells and upregulation of the stimulator of interferon genes (STING) is triggered by the generated ROS and Mn2+ from NPMCA, respectively, leading to activation of antitumor immune response. The potency of immune response is further reinforced by reducing the accumulation of adenosine in tumor microenvironment by the activated ADA. As a result, NPMCA enables CDT and SDT‐cooperated immunotherapy, showing an obviously improved therapeutic efficacy to inhibit the growths of bilateral tumors, in which the primary tumors are covered with 2‐cm tissues.

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy characterized by massive fibrosis and has ineffective adjuvant therapies. Here, we demonstrate the potential of angiotensin receptor blockers (ARBs) in targeting iCCA. Methods Masson's trichrome staining was used to assess the effect of ARBs in iCCA specimens, CCK8 and gel contraction assays in vitro and in xenograft models in vivo. RNA‐seq and ATAC‐seq were used for mechanistic investigations. Results Patients with iCCA who were administered ARBs had a better prognosis and a lower proportion of tumour stroma, indicating alleviated fibrosis. The presence of AGTR1, the ARBs receptor, is associated with a poor prognosis of iCCA and is highly expressed in tumour tissues and cancer‐associated fibroblasts (CAFs). The ARBs strongly attenuated the viability of AGTR1+CAFs in vitro and retarded tumour progression and fibrosis in xenograft models of co‐cultured CAFs and iCCA cells. Still, they did not have a significant effect on AGTR1−CAFs. Moreover, ARBs decreased the secretion of AGTR1+CAF‐derived MFAP5 via the Hippo pathway, weakened the interaction between CAFs and iCCA cells, and impaired the aggressiveness of iCCA cells by attenuating the activation of the Notch1 pathway in iCCA cells. Conclusions ARBs exhibit anti‐fibrotic function by inhibiting the viability of AGTR1+CAFs. These findings support using ARBs as a novel therapeutic option for targeting iCCA.

Abstract Introduction A high perceptual load can effectively prevent attention from being drawn to irrelevant stimuli; however, the neural pattern underlying this process remains unclear. Methods This study adopted a perceptual load paradigm to examine the temporal processes of attentional modulation by incorporating conditions of perceptual load, distractor‐target compatibility, and eccentricity. Results The behavioral results showed that a high perceptual load significantly reduced attentional distraction caused by peripheral distractors. The event‐related potential results further revealed that shorter P2 latencies were observed for peripheral distractors than for central distractors under a high perceptual load and that a suppressed compatibility effect with increasing load was reflected by the P3 component. Conclusion These findings suggested that (1) P2 and P3 components effectively captured different sides of attentional processing modulated by load (i.e., the filter processing of the object and the overall attentional resource allocation) and (2) response patterns of selective attention modulated by perceptual load were influenced by eccentricity. Our electrophysiological evidence confirmed the behavioral findings, indicating the neural mechanisms of attentional modulation.

Abstract Objective To explore the feasibility and clinical efficacy of a modified medial collateral ligament indentation technique in total knee arthroplasty (TKA) with severe type II valgus deformity. Methods Consecutive patients with Krackow type II valgus deformity >20° who underwent a primary unilateral TKA between May 2008 and June 2017 were studied retrospectively. A medial collateral ligament indentation technique was performed in 20 patients (MCLI group), and 23 patients received the routine lateral structures release technique (LSR group). Radiological parameters, such as the valgus angle (VA), and functional outcomes including the use of constraint implants, Knee Society Score (KSS), Knee Society Function score (KSF), and thickness of the polyethylene insert were compared between the two groups. Results A total of 43 consecutive patients had a minimum 2‐year follow‐up. The preoperative VA was comparable between the MCLI (23.5° ± 5.8°) and LSR groups (21.3° ± 3.2°, P = 0.134), as was the postoperative VA (1.1° ± 2.1° and 2.5° ± 3.0°, respectively, P = 0.084). The mean KSS and KSF scores in the MCLI group were 30.2 ± 4.8 and 38.8 ± 4.8, respectively, before surgery, and they increased to 91.3 ± 2.6 and 86.5 ± 2.4 at the last follow‐up. The scores in the LSR group were 31.5 ± 7.5 and 36.5 ± 7.8 before surgery and 92.4 ± 3.5 and 88.5 ± 3.6 at the last follow‐up. While no statistically significant differences in pre‐ or postoperative functional scores were found between the two groups, the MCLI group had thinner polyethylene inserts (9.5 ± 1.1 mm vs 12.9 ± 1.5 mm) and less use of constrained condylar inserts (15% vs 69.6%). During follow‐up, the MCLI group had fewer complications. Conclusion A modified MCLI technique can achieve good outcomes in TKA with type II valgus deformity of >20°. It can maintain a normal joint line level, reduce the use of constrained condylar knee prostheses, and is a reliable choice for severe genu valgum.

Abstract Background Emerging evidence has underscored infiltrating immune cells in the tumor microenvironment (TME) of non‐small cell lung cancer (NSCLC). Owing to screening programs, the prevalence of early‐stage NSCLC is growing, but its high recurrence risk and poor survival impose an increasing demand for further understanding the TME. Methods Tissue and plasma samples from 33 resectable stage IA NSCLC patients were collected from the surgery and subject to histological and genomic analyses. The distribution of CD8+ T cells, tumor‐associated macrophages (TAMs, M1 polarization and M2 polarization), and natural killer (NK) cells (CD56dim and CD56bright) was analyzed. The impact of clinical characteristics and immunotherapy‐related biomarkers on immune cell infiltration were also investigated. Results Using multiplex immunohistochemistry (mIHC), we found a significantly higher M1 polarization proportion of total TAMs in tumor parenchyma than in other tissues, while other immune cells remained stable. Patients under 50 showed higher infiltrating CD8+ T cell density and M1 ratio in tumor tissues. Tumors carrying RAS‐MAPK mutations were associated with significantly increased infiltration of CD8+ T cells. We also identified significantly higher infiltration of CD8+ T cells and enrichment of CD56bright NK cells in high tumor mutation burden (TMB) and high programmed cell death ligand 1 (PD‐L1) samples, respectively. Conclusions Our study highlighted the heterogeneity and dynamics of infiltrating immune cells in stage IA NSCLC TME, featured by M1 TAM enrichment in tumor parenchyma. Age, driver mutation type, TMB, and PD‐L1 level were found to associate with immune cell infiltration in the TME, shedding light on immunotherapy development.

Abstract Background The role of Numb, a protein that is important for cell fate and development and that, in human muscle, is expressed at reduced levels with advanced age, was investigated; adult mice skeletal muscle and its localization and function within myofibres were determined. Methods Numb expression was evaluated by western blot. Numb localization was determined by confocal microscopy. The effects of conditional knock out (cKO) of Numb and the closely related gene Numb‐like in skeletal muscle fibres were evaluated by in situ physiology, transmission and focused ion beam scanning electron microscopy, three‐dimensional reconstruction of mitochondria, lipidomics, and bulk RNA sequencing. Additional studies using primary mouse myotubes investigated the effects of Numb knockdown on cell fusion, mitochondrial function, and calcium transients. Results Numb protein expression was reduced by ~70% (P

Abstract With the increase in new energy power generation and the continuous augment in the penetration rate of electric vehicles, it is of crucial importance to use electric vehicles as energy storage devices to promote the consumption of new energy. Aiming at the uncertainty of electric vehicles, this paper proposes a method based on multiobjective optimization for electric vehicle‐supercapacitor hybrid energy storage system to track PV project output. The hybrid system consists of electric vehicles and supercapacitor. Electric vehicles and supercapacitors supplement the deviation of PV actual power and predicted power by charging and discharging. The electric vehicle is regarded as a nonspecific way to label a piece of equipment that can store energy. First and foremost, on the basis of traditional method of predicting PV output, a PSO‐BP prediction method based on PCA is proposed to improve the accuracy of PV output prediction. Secondarily, according to the different characteristics of electric vehicles and supercapacitors, the empirical mode decomposition (EMD) method is used to decompose the deviation that the hybrid energy storage system needs to bear with the purpose of initially allocating the energy. Furthermore, a multiobjective optimization model is established for the precise energy distribution of the hybrid energy storage system, and the NSGA‐III algorithm is used to solve it. Ultimately, the data of a domestic PV power station are used for simulation. After optimized control, the result shows that the standard deviation of the system output is reduced from 1967 to 75.77. The research in this article provides a theoretical basis for the application of electric vehicle virtual energy storage technology in the field of auxiliary new energy grid connection.

Abstract The gastrointestinal stromal tumour (GIST) is a common mesenchymal tumour that lacks specificity of clinical manifestations. Therefore, preoperative accurate localization and accurate prediction of tumour risk are of important clinical value. At present, the diagnosis of GIST relies mainly on manual annotation of CT by professional doctors, which is inefficient and affected by subjective factors. A GIST segmentation algorithm is proposed based on a convolutional neural network to fuse multi‐scale features. The algorithm is applied to GIST segmentation with an improved 3‐D U‐Net method. Skip connections are introduced between encoders and decoders at different layers to account for the obvious differences in tumour size between different cases, which increases the path of information transmission in the network and solves the problem that U‐Net is too weak to simultaneously extract the features of different scales. In addition, due to the difficulty of tumour labelling and the correlation between small intestine segmentation and GIST segmentation, the model of small intestine segmentation is transferred to the model of GIST segmentation. Experiments show that the proposed method achieves better performance than that of the traditional U‐Net. Finally, the graph neural network is introduced to reduce the repetitive work of doctors in refining the segmentation results.