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Abstract Objective To provide evidence for choosing surgical or nonsurgical treatment for epilepsy in patients with unilateral multilobar and hemispheric polymicrogyria (PMG). Methods We searched published studies until September 2022 related to unilateral multilobar and hemispheric PMG and included patients who were followed up at the Pediatric Epilepsy Centre of Peking University First Hospital in the past 10 years. We summarized the clinical characteristics and compared the long‐term outcomes after surgical or nonsurgical (anti‐seizure medications, ASMs) treatment. Results A total of 70 patients (49 surgical, 21 non‐surgical) with unilateral multilobar and hemispheric PMG were included. The median age at epilepsy onset was 2.5 years (1.0–4.1). The most common seizure types were focal and atypical absence seizures. In the whole cohort, 87.3% had hemiparesis and 67.1% had electrical status epilepticus during slow sleep (ESES). There were significant differences in age at epilepsy onset, extent of lesion, and EEG interictal discharges between the two groups. At the last follow‐up (median 14.1 years), the rates of seizure‐freedom (81.6% vs. 57.1%, p = 0.032) and ASM discontinuation (44.4% vs. 6.3%, p = 0.006) were higher in the surgical group than in the nonsurgical group. Patients in the surgical group had a higher rate of seizure‐freedom with complete resection/disconnection than with subtotal resection (87.5% vs. 55.6%, p = 0.078), but with no statistically significant difference. In the nonsurgical group, more extensive lesions were associated with worse seizure outcomes. Cognition improved postoperatively in 90% of surgical patients. Significance In patients with unilateral multilobar and hemispheric PMG, the age of seizure onset, the extent of the lesion and EEG features can help determine whether surgery should be performed early. Additionally, surgery could be more favorable for achieving seizure freedom and cognitive improvement sooner. Plain Language Summary We aim to summarize clinical characteristics and compare the long‐term outcomes after surgical and nonsurgical (ASM) treatment to provide a basis for treatment decisions for patients with unilateral multilobar and hemispheric polymicrogyria (PMG)‐related epilepsy. We found that patients with unilateral hemispheric and multilobar PMG had significantly higher rates of seizure freedom and ASM discontinuation with surgical treatment than with nonsurgical treatment. In the surgical group, seizure outcomes were better in patients treated with complete resection/disconnection than in those treated with subtotal resection, but the difference was not statistically significant.

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Its pathogenesis is not fully understood, and early diagnosis is challenging owing to the lack of effective biomarkers. This study aimed to analyze different samples to identify potential biomarkers and therapeutic targets. Methods Microarray datasets of RA, osteoarthritis (OA), and healthy control (HC) were downloaded from the Gene Expression Omnibus database. R software was used to identify differentially expressed genes (DEGs), which were visualized using volcano and heat maps. Venn diagrams, principal component analysis, gene set enrichment analysis, gene ontology, and Kyoto Encyclopedia of genes and genomes were used to analyze the data. A protein–protein interaction network was constructed, and synovial tissues from patients with RA and OA were collected for verification using the collagen‐induced arthritis mouse model. Results More DEGs were found in synovial tissues than in peripheral blood mononuclear cells or fibroblast‐like synoviocytes. Principal component analysis revealed significant differences between the RA and OA samples, highlighting the unique advantages of synovial tissue. Enrichment analysis revealed that metabolic and cytokine signaling pathways play crucial roles in the development of RA. Further analysis of the four synovial datasets identified 54 DEGs, of which signaling lymphocytic activation molecule family (SLAMF) 8 was identified as the key molecule. SLAMF8 levels were increased in the synovial tissue of patients with RA compared to those of patients with OA (0.38 ± 0.19 vs. 12.40 ± 1.66), and SLAMF8 levels were similarly elevated in collagen‐induced arthritis model mice compared with those in the healthy mice (1.13 ± 0.47 vs. 9.05 ± 2.52). Conclusions This study established the unique advantages of synovial tissue for RA research and identified metabolic and cytokine signaling pathways as important for RA development. Thus, SLAMF8 may be a potential therapeutic target for RA.

Abstract To investigate the significant deformation of the surrounding rock within the dynamic pressure zone of the gateroad, this study utilized the tailgate of the 1506 longwall face in Anyang Coal Mine as the engineering context. A combined approach of field measurement and numerical analysis was employed to explore the deformation and failure mechanisms of the surrounding rock under dynamic pressure. The findings indicate that before the exploitation of the 1506 longwall face, there was a notable reduction in stress across the floor and immediate roof, with minimal stress concentration observed in the coal pillar and the entity rib side. The plastic zone surrounding the tailgate was limited, suggesting a high degree of stability in the entry's surrounding rock. However, during the extraction of the 1506 longwall face, the tailgate, extending 60 m ahead of the working face, was subjected to dynamic pressure, leading to a marked increase in stress within the floor, coal pillar, and immediate roof. Stress concentration was more pronounced on the entity rib side than on the pillar rib side. This resulted in significant fissuring and severe deformation of the entry's surrounding rock. The primary failure mechanism involved damage to both the roof and floor corners, with the severity of damage escalating alongside the stress in the surrounding rock. This culminated in the failure of roof corner bolts and anchor cables, thereby compromising the stability of the entry within the dynamic pressure zone.

Abstract Graphene films grown by the chemical vapor deposition (CVD) method suffer from contamination and damage during transfer. Herein, an innovative ice‐enabled transfer method under an applied electric field and in the presence of Cu2O (or Cu2O‐Electric‐field Ice Transfer, abbreviated as CEIT) is developed. Ice serves as a pollution‐free transfer medium while water molecules under the electric field fully wet the graphene surface for a bolstered adhesion force between the ice and graphene. Cu2O is used to reduce the adhesion force between graphene and copper. The combined methodology in CEIT ensures complete separation and clean transfer of graphene, resulting in successfully transferred graphene to various substrates, including polydimethylsiloxane (PDMS), Teflon, and C4F8 without pollution. The graphene obtained via CEIT is utilized to fabricate field‐effect transistors with electrical performances comparable to that of intrinsic graphene characterized by small Dirac points and high carrier mobility. The carrier mobility of the transferred graphene reaches 9090 cm2 V−1 s−1, demonstrating a superior carrier mobility over that from other dry transfer methods. In a nutshell, the proposed clean and efficient transfer method holds great potential for future applications of graphene.

ABSTRACT Background Non–small cell lung cancer (NSCLC) is one of the cancers with the highest mortality and morbidity in the world. Circular RNAs (circRNAs) are newly identified players in carcinogenesis and development of various cancers. This study is aimed at exploring the functional effects and mechanism of circ_0028826 in the development of NSCLC. Methods Real‐time quantitative PCR (RT‐qPCR) was used to detect the expression levels of circ_0028826, IDH2 mRNA, and miR‐758‐3p. IDH2, Bcl2, Bax, and E‐cadherin protein levels were detected using a western blot. Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays were used to assess the capacities of proliferation, apoptosis, migration, and invasion. Interaction between miR‐758‐3p and circ_0028826 or IDH2 was validated using a dual‐luciferase reporter assay. The role of circ_0028826 in vivo was checked based on a xenograft tumor model. Results Circ_0028826 was elevated in NSCLC, and its absence inhibited NSCLC cell proliferation, migration, invasion, and induced apoptosis. In terms of mechanism, circ_0028826 increased IDH2 expression by targeting miR‐758‐3p. In addition, circ_0028826 knockdown also regulated IDH2 by targeting miR‐758‐3p to inhibit tumor growth in vivo. Conclusion Circ_0028826 promoted the development of NSCLC via regulation of the miR‐758‐3p/IDH2 axis, providing a new strategy for NSCLC treatment.

Abstract Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine‐selective warheads face challenges due to cross‐reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro‐ or phenoxy‐substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy‐NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH‐overexpressed cancer cells. Conversely, alkoxy‐NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti‐interfering ability against thiols. Leveraging a proximity‐driven approach, alkoxy‐NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

Abstract The extensive application of nuclear technology has increased the potential of uncontrolled radiation exposure to the public. Since skin is the largest organ, radiation‐induced skin injury remains a serious medical concern. Organisms evolutionally develop distinct strategies to protect against environment insults and the related research may bring novel insights into therapeutics development. Here, 26 increased peptides are identified in skin tissues of frogs (Pelophylax nigromaculatus) exposed to electron beams, among which four promoted the wound healing of irradiated skin in rats. Specifically, radiation‐induced frog skin peptide‐2 (RIFSP‐2), from histone proteolysis exerted membrane permeability property, maintained cellular homeostasis, and reduced pyroptosis of irradiated cells with decreased TBK1 phosphorylation. Subsequently, stearyl‐CoA desaturase 1 (SCD1) is identified, a critical enzyme in biogenesis of monounsaturated fatty acids (MUFAs) as a direct target of RIFSP‐2 based on streptavidin‐biotin system. The lipidomic analysis further assured the restrain of MUFAs biogenesis by RIFSP‐2 following radiation. Moreover, the decreased MUFA limited radiation‐induced and STING‐mediated inflammation response. In addition, genetic depletion or pharmacological inhibition of STING counteracted the decreased pyroptosis by RIFSP‐2 and retarded tissue repair process. Altogether, RIFSP‐2 restrains radiation‐induced activation of SCD1‐MUFA‐STING axis. Thus, the stress‐induced amphibian peptides can be a bountiful source of novel radiation mitigators.

Abstract FOXG1 syndrome is a developmental encephalopathy caused by FOXG1 (Forkhead box G1) mutations, resulting in high phenotypic variability. However, the upstream transcriptional regulation of Foxg1 expression remains unclear. This report demonstrates that both deficiency and overexpression of Men1 (protein: menin, a pathogenic gene of MEN1 syndrome known as multiple endocrine neoplasia type 1) lead to autism‐like behaviors, such as social defects, increased repetitive behaviors, and cognitive impairments. Multifaceted transcriptome analyses revealed that Foxg1 signaling is predominantly altered in Men1 deficiency mice, through its regulation of the Alpha Thalassemia/Mental Retardation Syndrome X‐Linked (Atrx) factor. Atrx recruits menin to bind to the transcriptional start region of Foxg1 and mediates the regulation of Foxg1 expression by H3K4me3 (Trimethylation of histone H3 lysine 4) modification. The deficits observed in menin deficient mice are rescued by the over‐expression of Foxg1, leading to normalized spine growth and restoration of hippocampal synaptic plasticity. These findings suggest that menin may have a putative role in the maintenance of Foxg1 expression, highlighting menin signaling as a potential therapeutic target for Foxg1‐related encephalopathy.

Abstract The regulation of PD‐L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD‐L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD‐L1 expression and protein stability, and the deubiquitinase ubiquitin‐specific peptidase 22 (USP22) is identified as a key mediator in this process. EZH2 inhibition transcriptionally upregulates USP22 expression, and upregulated USP22 further stabilizes PD‐L1. Importantly, a combination of EZH2 inhibitors with anti‐PD‐1 immune checkpoint blockade therapy improves the tumor microenvironment, enhances sensitivity to immunotherapy, and exerts synergistic anticancer effects. In addition, knocking down USP22 can potentially enhance the therapeutic efficacy of EZH2 inhibitors on colon cancer. These findings unveil the novel role of EZH2 inhibitors in tumor immune evasion by upregulating PD‐L1, and this drawback can be compensated by combining ICI immunotherapy. Therefore, these findings provide valuable insights into the EZH2‐USP22‐PD‐L1 regulatory axis, shedding light on the optimization of combining both immune checkpoint blockade and EZH2 inhibitor‐based epigenetic therapies to achieve more efficacies and accuracy in cancer treatment.

Abstract Fluorescent‐patterned materials are widely used in information storage and encryption. However, preparing a patterned fluorescent display on a matrix currently requires a time‐consuming (hours or even days) and complex multi‐step process. Herein, a rapid and mild technique developed for the in‐situ controllable synthesis of fluorescent nitrogen‐doped carbon dots (NCDs) on eco‐friendly transparent wood films (TEMPO‐oxidized carboxyl wood film [TOWF]) within a few minutes was developed. A wood skeleton was employed as the carbon precursor for NCD synthesis as well as the matrix for the uniform and controlled distribution of NCDs. Moreover, the in‐situ synthesis mechanism for preparing NCDs in TOWF was proposed. The resulting fluorescent wood films have excellent tensile strength (310.00 ± 15.57 MPa), high transmittance (76.2%), high haze (95.0%), UV‐blocking properties in the full ultraviolet (UV) range, and fluorescent performance that can be modified by changing the heating parameters. Fluorescent patterning was simply achieved by regulating the in‐situ NCD synthesis regions, and the fluorescent patterns were formed within 10 s. These fluorescent‐patterned wood films can effectively store and encrypt information, and they can interact with external information through a transparent matrix. This work provides a green and efficient strategy for fabricating fluorescent information storage and encryption materials.

Abstract Recent studies have reported the role of the M3 muscarinic acetylcholine receptor (M3R), a member of the G‐protein coupled receptor superfamily, encoded by the CHRM3 gene, in cardiac function and the regulation of blood pressure (BP). The aim of this study was to investigate the associations of CHRM3 genetic variants with salt sensitivity, longitudinal BP changes, and the development of hypertension in a Chinese population. We conducted a chronic dietary salt intervention experiment in a previously established Chinese cohort to analyze salt sensitivity of BP. Additionally, a 14‐year follow‐up was conducted on all participants in the cohort to evaluate the associations of CHRM3 polymorphisms with longitudinal BP changes, as well as the incidence of hypertension. The single nucleotide polymorphism (SNP) rs10802811 within the CHRM3 gene displayed significant associations with low salt‐induced changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), while rs373288072, rs114677844, and rs663148 exhibited significant associations with SBP and MAP responses to a high‐salt diet. Furthermore, the SNP rs58359377 was associated with changes in SBP and pulse pressure (PP) over the course of 14 years. Additionally, the 14‐year follow‐up revealed a significant association between the rs619288 polymorphism and an increased risk of hypertension (OR = 1.74, 95% CI: 1.06‐2.87, p = .029). This study provides evidence that CHRM3 may have a role in salt sensitivity, BP progression, and the development of hypertension.

Abstract In China, several problems were common in the telemedicine systems, such as the poor network stability and difficult interconnection. A new telemedicine system jointly driven by multinetwork integration and remote control has been designed to address these problems. A multilink aggregation algorithm and an overlay network for telemedicine system (ONTMS) were developed to improve network stability, and a non‐intervention remote control method was designed for Internet of Things (IoT) devices/systems. The authors monitored the network parameters, and distributed the questionnaire to participants, for evaluating the telemedicine system and services. Under a detection bandwidth of 8 Mbps, the aggregation parameters of Unicom 4G, Telecom 4G, and China Mobile 4G were optimal, with an uplink bandwidth, delay, and packet loss ratio (PLR) of 7.93 Mbps, 58.80 ms, and 0.06%, respectively. These parameters were significantly superior to those of China Mobile 4G, the best single network (p < 0.001). Through the ONTMS, the mean round‐trip transporting delay from Beijing to Sanya was 76 ms, and the PLR was 0 at vast majority of time. A total of 1988 participants, including 1920 patients and 68 doctors, completed the questionnaires. More than 97% of participants felt that the audio and video transmission and remote control were fluent and convenient. 96% of patients rated the telemedicine services with scores of 4 or 5. This system has shown robust network property and excellent interaction ability, and satisfied the needs of patients and doctors.

Abstract According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell‐mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA‐mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA‐ERK1/2‐ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA‐treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.

Background Although cardiovascular mortality continued declining from 2000 to 2019, the rate of this decrease decelerated. We aimed to assess the trends and disparities in risk factor control and treatment among US adults with atherosclerotic cardiovascular disease to find potential causes of the deceleration. Methods and Results A total of 55 ,021 participants, aged ≥20 years, from the 1999 to 2018 National Health and Nutrition Examination Survey were included, of which 5717 were with atherosclerotic cardiovascular disease. Risk factor control was defined as hemoglobin A1c

Abstract Acoustic communication plays important roles in the survival and reproduction of anurans. The perception and discrimination of conspecific sound signals of anurans were always affected by masking background noise. Previous studies suggested that some frogs evolved the high‐frequency hearing to minimize the low‐frequency noise. However, the molecular mechanisms underlying the high‐frequency hearing in anurans have not been well explored. Here, we cloned and obtained the coding regions of a high‐frequency hearing‐related gene (KCNQ4) from 11 representative anuran species and compared them with orthologous sequences from other four anurans. The sequence characteristics and evolutionary analyses suggested the highly conservation of the KCNQ4 gene in anurans, which supported their functional importance. Branch‐specific analysis showed that KCNQ4 genes were under different evolutionary forces in anurans and most anuran lineages showed a generally strong purifying selection. Intriguingly, one significantly positively selected site was identified in the anuran KCNQ4 gene based on FEL model. Positive selection was also found along the common ancestor of Ranidae and Rhacophoridae as well as the ancestral O. tianmuii based on the branch‐site analysis, and the positively selected sites identified were involved in or near the N‐terminal ion transport and the potassium ion channel functional domain of the KCNQ4 genes. The present study revealed valuable information regarding the KCNQ4 genes in anurans and provided some new insights for the underpinnings of the high‐frequency hearing in frogs.

Abstract The development of magnetocaloric materials with a significantly enhanced volumetric cooling capability is highly desirable for the application of adiabatic demagnetization refrigerators in confined spatial environments. Here, the thermodynamic characteristics of a magnetically frustrated spin‐7/2 Gd9.33[SiO4]6O2 is presented, which exhibits strongly correlated spin disorder below ≈1.5 K. A quantitative model is proposed to describe the magnetization results by incorporating nearest‐neighbor Heisenberg antiferromagnetic and dipolar interactions. Remarkably, the recorded magnetocaloric responses are unprecedentedly large and applicable below 1.0 K. It is proposed that the S = 7/2 spin liquids serve as versatile platforms for investigating high‐performance magnetocaloric materials in the sub‐kelvin regime, particularly those exhibiting a superior cooling power per unit volume.

Abstract Inadequate β‐cell mass and insulin secretion are essential for the development of type 2 diabetes (T2D). TNF‐α‐induced protein 8‐like 1 (Tipe1) plays a crucial role in multiple diseases, however, a specific role in T2D pathogenesis remains largely unexplored. Herein, Tipe1 as a key regulator in T2D, contributing to the maintenance of β cell homeostasis is identified. The results show that the β‐cell‐specific knockout of Tipe1 (termed Ins2‐Tipe1BKO) aggravated diabetic phenotypes in db/db mice or in mice with high‐fat diet‐induced diabetes. Notably, Tipe1 improves β cell mass and function, a process that depends on Gαs, the α subunit of the G‐stimulating protein. Mechanistically, Tipe1 inhibited the K48‐linked ubiquitination degradation of Gαs by recruiting the deubiquitinase USP5. Consequently, Gαs or cAMP agonists almost completely restored the dysfunction of β cells observed in Ins2‐Tipe1BKO mice. The findings characterize Tipe1 as a regulator of β cell function through the Gαs/cAMP pathway, suggesting that Tipe1 may emerge as a novel target for T2D intervention.

Abstract Objective The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. Methods The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Results Median follow‐up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5‐year OS and disease‐free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p

Abstract Background In recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC. Methods We screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR‐1470 in healthy volunteers and CRC patients were analyzed using qRT‐PCR. To evaluate the diagnostic potential of the selected miR‐1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR‐1470 in CRC cell lines, we detected the miR‐1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR‐1470 in SW480, HCT‐116 cells. Results Exosomal miR‐1470 exhibited significant up‐regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876–0.7920) for exosomal miR‐1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR‐1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR‐1470 in CRC cell lines. CCK8 proliferation assay showed that miR‐1470 promoted the proliferation ability of SW480 and HCT‐116 cells. Transwell assay showed that miR‐1470 promoted the migration and invasion ability of SW480 and HCT‐116 cells. Conclusion This suggested that non‐invasive diagnosis of CRC is possible by detecting the level of miR‐1470 in exosomes, which has important implications for early detection and treatment of this disease.

Abstract Detrusor underactivity (DUA) is a common and thorny problem in urology, which severely impairs patients’ bladder function and quality of life. However, its underlying pathophysiological mechanism remains unclear. Hence, we sequenced 69,973 cells from five controls and nine patients with bladder dysfunction using single‐cell RNA sequencing. Twelve distinct cell types were identified and they showed high cellular and functional heterogeneity among each group. Among them, fibroblasts, macrophages, and epithelial cells had the most intercellular communications. Their aberrant gene expressions and altered intercellular interactions were mainly involved in extracellular matrix organization, inflammation/immune regulation, and cellular injury. Further re‐cluster analysis revealed an accumulation of the RBFOX1+ fibroblasts and RIPOR2+ macrophages in dysfunctional bladder wall, which mediated bladder remodeling through dysfunctional extracellular matrix organization and inflammation/immune reaction. Besides, the subtype of the epithelial cells was significantly altered. They underwent an intricate process including inflammation, damage, and repair during bladder remodeling. Overall, this work constructed the first single‐cell atlas for obstruction‐induced DUA, which could provide a valuable resource for deciphering the cellular heterogeneity and function changes in DUA, as well as potential strategies for bladder function improvement.

Abstract Breast cancer classification and segmentation play an important role in identifying and detecting benign and malignant breast lesions. However, segmentation and classification still face many challenges: 1) The characteristics of cancer itself, such as fuzzy edges, complex backgrounds, and significant changes in size, shape, and intensity distribution make accurate segment and classification challenges. 2) Existing methods ignore the potential relationship between classification and segmentation tasks, due to the classification and segmentation being treated as two separate tasks. To overcome these challenges, in this paper, a novel Semantic‐aware transformer (SaTransformer) for breast cancer classification and segmentation is proposed. Specifically, the SaTransformer enables doing the two takes simultaneously through one unified framework. Unlike existing well‐known methods, the segmentation and classification information are semantically interactive, reinforcing each other during feature representation learning and improving the ability of feature representation learning while consuming less memory and computational complexity. The SaTransformer is validated on two publicly available breast cancer datasets – BUSI and UDIAT. Experimental results and quantitative evaluations (accuracy: 97.97%, precision: 98.20%, DSC: 86.34%) demonstrate that the SaTransformer outperforms other state‐of‐the‐art methods.

Abstract The maintenance of wind farms is one of the major factors affecting their profitability. During preventive maintenance, the shutdown of wind turbines causes downtime energy losses. The selection of when and which turbines to maintain can significantly impact the overall downtime energy loss. This paper leverages a wind farm power generation model to calculate downtime energy losses during preventive maintenance for an offshore wind farm. Wake effects are considered to accurately evaluate power output under specific wind conditions. In addition to wind speed and direction, the influence of wake effects is an important factor in selecting time windows for maintenance. To minimize the overall downtime energy loss of an offshore wind farm caused by preventive maintenance, a mixed‐integer nonlinear optimization problem is formulated and solved by the genetic algorithm, which can select the optimal maintenance time windows of each turbine. Weather conditions are imposed as constraints to ensure the safety of maintenance personnel and transportation. Using the climatic data of Cape Cod, Massachusetts, the schedule of preventive maintenance is optimized for a simulated utility‐scale offshore wind farm. The optimized schedule not only reduces the annual downtime energy loss by selecting the maintenance dates when wind speed is low but also decreases the overall influence of wake effects within the farm. The portion of downtime energy loss reduced due to consideration of wake effects each year is up to approximately 0.2% of the annual wind farm energy generation across the case studies—with other stated opportunities for further profitability improvements.

Abstract Background Three‐dimensional visualization preoperative evaluation (3D‐VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D‐VPE and ERAS would improve the outcome of patients undergoing surgery for GBC. Objective This study aimed to determine if 3D‐VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC. Methods A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D‐VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups. Results Patients who underwent 3D‐VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p

Abstract Background Pathogenic germline variants (PGVs) can play a vital role in the oncogenesis process in carriers. Previous studies have recognized that PGVs contribute to early onset of tumorigenesis in certain cancer types, for example, colorectal cancer and breast cancer. However, the reported prevalence data of cancer‐associated PGVs were highly inconsistent due to nonuniform patient cohorts, sequencing methods, and prominent difficulties in pathogenicity interpretation of variants. In addition to the above difficulties, due to the rarity of cases, the prevalence of cancer PGV carriers in young cancer patients affected by late‐onset cancer types has not been comprehensively evaluated to date. Methods A total of 131 young cancer patients (1–29 years old at diagnosis) were enrolled in this study. The patients were affected by six common late‐onset cancer types, namely, lung cancer, liver cancer, colorectal cancer, gastric cancer, renal cancer, and head–neck cancer. Cancer PGVs were identified and analyzed. based on NGS‐based targeted sequencing followed by bioinformatic screening and strict further evaluations of variant pathogenicity. Results Twenty‐three cancer PGVs in 21 patients were identified, resulting in an overall PGV prevalence of 16.0% across the six included cancer types, which was approximately double the prevalence reported in a previous pancancer study. Nine of the 23 PGVs are novel, thus expanding the cancer PGV spectrum. Seven of the 23 (30.4%) PGVs are potential therapeutic targets of olaparib, with potential implications for clinical manipulation. Additionally, a small prevalence of somatic mutations of some classic cancer hallmark genes in young patients, in contrast to all‐age patients, was revealed. Conclusion This study demonstrates the high prevalence of PGVs in young cancer patients with the common late‐onset cancers and the potentially significant clinical implications of cancer PGVs, the findings highlight the value of PGV screening in young patients across lung cancer, liver cancer, colorectal cancer, gastric cancer, renal cancer, or head–neck cancer.

Abstract Objective Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a new and rare histopathological entity of cortical developmental malformations. The clinical characteristics of MOGHE remain challenging. Methods Children with histologically confirmed MOGHE were retrospectively studied. The clinical findings, electroclinical and imaging features, and postoperative outcomes were analyzed, and previously published studies were reviewed up to June 2022. Results Thirty‐seven children were included in our cohort. Clinical characteristics included early onset in infancy (94.6% before 3 years), multiple seizure types, and moderate or severe delay. Epileptic spasm is the most common seizure type and initial manifestation. The lesions were mainly multilobar (59.5% multiple lobes and 8.1% hemispheres), and predominance in the frontal lobe was observed. The interictal EEG pattern was circumscribed or widespread. The prominent MRI characteristics were cortical thickening, cortical/subcortical hyperintense T2/FLAIR signal, and blurring at the GM and WM transition. Among the 21 children followed up for more than 1 year after surgery, 76.2% were seizure‐free. Preoperative interictal circumscribed discharges and larger resections were significantly associated with a good postoperative outcome. The clinical features of 113 patients in the reviewed studies were similar to those we reported, but the lesions were mainly unilobar (73.5%) and Engel I was achieved in only 54.2% after surgery. Significance Distinct clinical characteristics in MOGHE, especially age at onset, epileptic spasm, and age‐related MRI characteristics, can help in early diagnosis. Preoperative interictal discharge and surgical strategy may be predictors of postoperative outcomes.

Abstract T‐2 toxin causes renal dysfunction with proteinuria and glomerular podocyte damage. This work explores the role of metabolic disorder/reprogramming‐mediated epigenetic modification in the progression of T‐2 toxin‐stimulated podocyte injury. A metabolomics experiment is performed to assess metabolic responses to T‐2 toxin infection in human podocytes. Roles of protein O‐linked‐N‐acetylglucosaminylation (O‐GlcNAcylation) in regulating T‐2 toxin‐stimulated podocyte injury in mouse and podocyte models are assessed. O‐GlcNAc target proteins are recognized by mass spectrometry and co‐immunoprecipitation experiments. Moreover, histone acetylation and autophagy levels are measured. T‐2 toxin infection upregulates glucose transporter type 1 (GLUT1) expression and enhances hexosamine biosynthetic pathway in glomerular podocytes, resulting in a significant increase in β‐arrestin‐1 O‐GlcNAcylation. Decreasing β‐arrestin‐1 or O‐GlcNAc transferase (OGT) effectively prevents T‐2 toxin‐induced renal dysfunction and podocyte injury. Mechanistically, O‐GlcNAcylation of β‐arrestin‐1 stabilizes β‐arrestin‐1 to activate the mammalian target of rapamycin (mTOR) pathway as well as to inhibit autophagy during podocyte injury by promoting H4K16 acetylation. To sum up, OGT‐mediated β‐arrestin‐1 O‐GlcNAcylation is a vital regulator in the development of T‐2 toxin‐stimulated podocyte injury via activating the mTOR pathway to suppress autophagy. Targeting β‐arrestin‐1 or OGT can be a potential therapy for T‐2 toxin infection‐associated glomerular injury, especially podocyte injury.

Abstract Interactions between oncogenic proteins contribute to the phenotype and drug resistance. Here, EZH2 (enhancer of zest homolog 2) is identified as a crucial factor that mediates HIF‐1 (hypoxia‐inducible factor) inhibitor resistance. Mechanistically, targeting HIF‐1 enhanced the activity of EZH2 through transcription activation of SUZ12 (suppressor of zest 12 protein homolog). Conversely, inhibiting EZH2 increased HIF‐1α transcription, but not the transcription of other HIF family members. Additionally, the negative feedback regulation between EZH2 and HIF‐1α is confirmed in lung cancer patient tissues and a database of cell lines. Moreover, molecular prediction showed that a newly screened dual‐target compound, DYB‐03, forms multiple hydrogen bonds with HIF‐1α and EZH2 to effectively inhibit the activity of both targets. Subsequent studies revealed that DYB‐03 could better inhibit migration, invasion, and angiogenesis of lung cancer cells and HUVECs in vitro and in vivo compared to single agent. DYB‐03 showed promising antitumor activity in a xenograft tumor model by promoting apoptosis and inhibiting angiogenesis, which could be almost abolished by the deletion of HIF‐1α and EZH2. Notably, DYB‐03 could reverse 2‐ME2 and GSK126‐resistance in lung cancer. These findings clarified the molecular mechanism of cross‐regulation of HIF‐1α and EZH2, and the potential of DYB‐03 for clinical combination target therapy.

Abstract Dysfunction of parvalbumin (PV) neurons is closely involved in depression, however, the detailed mechanism remains unclear. Based on the previous finding that multiple endocrine neoplasia type 1 (Protein: Menin; Gene: Men1) mutation (G503D) is associated with a higher risk of depression, a Menin‐G503D mouse model is generated that exhibits heritable depressive‐like phenotypes and increases PV expression in brain. This study generates and screens a serial of neuronal specific Men1 deletion mice, and found that PV interneuron Men1 deletion mice (PcKO) exhibit increased cortical PV levels and depressive‐like behaviors. Restoration of Menin, knockdown PV expression or inhibition of PV neuronal activity in PV neurons all can ameliorate the depressive‐like behaviors of PcKO mice. This study next found that ketamine stabilizes Menin by inhibiting protein kinase A (PKA) activity, which mediates the anti‐depressant function of ketamine. These results demonstrate a critical role for Menin in depression, and prove that Menin is key to the antidepressant function of ketamine.

Background. Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research. Materials and Methods. A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein–protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes. Results. Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene. Conclusions. Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.

The variational inequality framework holds significant prominence across various domains including economic finance, network transportation, and game theory. In addition, a novel approach utilizing a neural network model is introduced in the current work to address a box constrained variational inequality problem. Initially, the original problem is reformulated into a nonsmooth equation, following which the neural network model is meticulously devised to tackle this reformulated equation. This study comprehensively investigated inherent characteristics and properties of this neural network model. In addition, employing the Lyapunov function method, stability analysis of the neural network model proposed is rigorously demonstrated in the Lyapunov sense. Furthermore, the efficacy of the proposed technique is substantiated through numerical simulations, providing empirical support for its applicability and effectiveness.

To investigate the mechanical properties of carbon-fiber-reinforced-polymer (CFRP)-restrained concrete in a saline soil environment, the degradation of the mechanical properties of CFRP-restrained concrete columns under the effect of continuous sulfate semisoak erosion is investigated based on sulfate continuous semisoak erosion, and unrestrained concrete columns with the same specifications are used in comparison tests. The results show that the strength, stiffness, and ductility of both plain concrete columns and CFRP-confined concrete columns first increase and then decrease after the continuous semi-submersion erosion by sulfate; compared with plain concrete columns, the decline rates of strength and stiffness of CFRP-confined concrete columns are significantly lower, and the CFRP demonstrates a certain protective effect on the core concrete. Through a regression analysis of experimental data, strength and ultimate strain models of CFRP-confined concrete columns under the continuous semi-submergence of sulfate are proposed based on the existing ultimate strength and ultimate strain models of CFRP-confined ordinary concrete columns, and a stress–strain model of CFRP-confined concrete columns under the continuous semi-submergence of sulfate is established. Based on a comparison with experimental data, the model prediction curves indicate good agreement with the experimental curves and can therefore provide a theoretical basis and practical reference for CFRP-reinforced semi-submerged concrete in saline soil areas.

Abstract Sweet potato stem nematode disease is a devastating disease, which seriously affects the yield and quality of sweet potato (Ipomoea batatas (L.) Lam.). At present, soil treatment with pesticides is mainly used to prevent sweet potato stem nematode disease. In this study, Illumina MiSeq high‐throughput sequencing technology was used to analyze the diversity of soil bacterial and fungal communities treated with different pesticides. At the same time, high performance liquid chromatography was used to determine the pesticide residues in soil and sweet potato, and the impact on sweet potato yield was investigated. Kruskal–Wallis test was used to analyze the four α‐diversity indexes of soil under different pesticide treatments, and the differences were not significant (p > 0.05), indicating that there was no significant difference in the diversity and abundance of bacterial and fungal communities in soil under different pesticide treatments. The results of principal coordinate analysis showed that there was no significant difference in bacterial and fungal community structure among different pesticide treatments (p > 0.05). Pesticide residue analysis and yield statistics of sweet potato showed that the residual amount of three kinds of pesticides in sweet potato did not exceed the maximum limit stipulated by the current National Standards for Food safety (GB2763‐2021). When 5% chlorpyrifos phoxim particles were applied at 15.18 kg/acre, sweet potato was unaffected by pests and diseases basically, and the yield was the highest.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive genetic disease characterized by clinical symptoms such as eczema, thrombocytopenia with small platelets, immune deficiency, prone to autoimmune diseases, and malignant tumors. This disease is caused by mutations of the WAS gene encoding WASprotein (WASP). The locus and type of mutations of the WAS gene and the expression quantity of WASP were strongly correlated with the clinical manifestations of patients. We found a novel mutation in the WAS gene (c.931+5G>C), which affected splicing to produce three abnormal mRNA, resulting in an abnormally truncated WASP. This mutation led to a reduction but not the elimination of the normal WASP population, resulting in causes X-linked thrombocytopenia (XLT) with mild clinical manifestations. Our findings revealed the pathogenic mechanism of this mutation.

Background. The long-term exposure to ultraviolet radiation (UVR) raises oxidative stress and chronic inflammation levels, which in turn has a series of deleterious effects on skin health, such as sunburn, photoaging, and skin cancer. Hence, our study was determined to investigate the effects and mechanisms of epigallocatechin gallate (EGCG) in zebrafish and human skin fibroblasts (HSF) cells to alleviate ultraviolet-induced photoaging. Methods. The 4 days postfertilization (dpf) zebrafish larvae and HSF cells were treated with 10 J/cm2 UVA + 30 mJ/cm2 UVB, or 25, or 50 μM EGCG for 72 hr. The indicators involving in oxidative stress, inflammatory, and photoaging were measured by the kits, ELISA Kits and western blot methods. Results. EGCGs protect against UVR-induced skin damage in zebrafish and HSF cells. EGCG markedly decreased the reactive oxygen species (ROS), malondialdehyde, 8-OHdG levels, increased superoxide dismutase (SOD) activity, and significantly inhibited inflammatory factors levels including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), interleukin-6 (IL-6) in zebrafish, and HSF cells irradiated with UVR. We found that EGCG could reduce UVR-induced p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation and effectively inhibited the activity of the transcriptional factor nuclear factor-κB (NF-κB), thereby reducing the protein-1 (AP-1), TNF-α, IL-1α, IL-6, and matrix metalloproteinase-1 (MMP-1) expressions, which are critical mediators of skin aging cascade causing the photoaging. Conclusion. These results validate that EGCG for protection of photoaging in zebrafish and HSF cells induced by UVR, which is closely related to the regulation of p38 MAPK/NF-κB, AP-1 signaling pathway which relieve oxidative stress, inflammation, and collagen degradation.

Background. Catheter ablation failure poses a clinical challenge for epicardial or intramural ventricular arrhythmia (VA); however, guidewire ablation within the coronary venous system (CVS) may be effective and safe for targeting VAs. Methods. The ex vivo phase included four steps. In step 1, the steam pop incidence rates during guidewire ablation at power settings of 5, 10, 15, 20, and 25 W were analyzed using 10 mm- and 20 mm-tip guidewires. In step 2, guidewire ablation was performed for application durations of 10, 20, 30, 40, 50, 60, and 90 s, and the lesion size was measured. In step 3, the effects of saline infusion (0, 1, 2, 3, and 4 mL/min) on lesion dimensions and steam pop formation were examined. In step 4, an orthogonal array was constructed to obtain the optimal guidewire ablation parameters. In the in vivo phase, guidewire ablation within the CVS was performed in three dogs, and the lesion features in 10 days after ablation were observed. Results. In step 1, the steam pop incidence rates at 5, 10, 15, 20, and 25 W were 0%, 0%, 12.5%, 62.5%, and 100% using the 10 mm-tip guidewires and 0%, 0%, 0%, 25%, and 75% using the 20 mm-tip guidewires, respectively. In step 2, we found that the lesion areas increased with an increase in the ablation duration (the maximum lesion diameters at 30, 60, and 90 s were 4.9 ± 0.4, 7.0 ± 0.8, and 9.2 ± 0.7 mm in the 10 mm group and 3.2 ± 0.5, 4.5 ± 0.4, and 5.3 ± 0.7 mm in the 20 mm-tip group, respectively). In step 3, we observed that saline infusion was negatively correlated with ablation lesions but had a lower risk of steam pop. The optimal parameters for the 20 mm-tip guidewire ablation were 15 W, 50 s, and 2 mL/min or 20 W, 70 s, and 2 mL/min. In the in vivo phase, effective ablation lesions with maximum and minimum diameters of 3.2 ± 0.3 and 2.8 ± 0.5 mm, respectively, were created by the guidewires during the 10-day observation period after ablation. Conclusion. This novel radiofrequency guidewire ablation technique can feasibly create effective lesions within the CVS, which may improve the efficacy of catheter ablation for challenging epicardial or intramural VA.

Abstract Background Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)‐positive subtype. This meta‐analysis aimed to objectively explore the efficacy and safety of TKIs. Methods Electronic databases were searched for relevant clinical trials. We conducted a pairwise meta‐analysis, pooled analysis, and estimated summary survival curves to compare survival outcomes following TKIs therapy for BCBM patients using Stata version 16.0 or R x64 4.0.5. Results Thirteen clinical trials involving 987 HER2‐positive BCBM patients were analyzed. A trend of longer progression‐free survival (PFS) was observed in the TKI‐containing arm compared to the non‐TKI‐containing arm (hazard ratio = 0.64, 95% confidence interval [CI]: 0.35–1.15, p = 0.132), although the difference is not statistically significant. Summary survival curves reported the summary median PFS and overall survival were 7.9 months and 12.3 months. Subgroup analysis revealed that TKIs combined with capecitabine (TKI + Cap) regimens resulted in improved survival outcomes. Tucatinib may be more effective in BCBM patients. The main grade 3–5 adverse events (AEs) were diarrhea (22%, 95% CI: 14%–32%), neutropenia (11%, 95% CI: 5%–18%), hepatic toxicity (7%, 95% CI: 1%–16%), and sensory neuropathy (6%, 95% CI: 2%–12%). Conclusion TKIs therapy improved the survival outcomes of HER2‐positive BCBM patients, especially when combined with capecitabine and tolerable AEs. We also identified the clinical value of tucatinib, which appears to be the most favorable TKI drug for BCBM patients.

Abstract Background Numerous studies have shown that the insulin‐like growth factor (IGF) pathway is highly associated with tumor initial and progression in several tumors. However, compared with IGF1/1R and IGF2/2R, insufficient studies have focused on IGF‐binding proteins (IGFBPs). Methods The GDC TCGA and GTEx data of 33 cancers, TCGA pan‐cancer immune phenotypes, tumor mutation burdens, and the copy number alterations of IGFBPs were extracted. Next, the prognostic value of IGFBPs was analyzed based on a univariate Cox analysis. Additionally, the ESTIMATE algorithm was used to calculate stromal and immune scores and tumor purity, and the CIBERSORT algorithm was used to estimate tumor‐infiltrating immunocyte levels. Ultimately, the correlation between IGFBP expression and cancer hallmark pathways was estimated with a Spearman analysis. Results The expression of IGFBPs was differentially expressed and correlated with prognosis in specific cancers. IGFBPs may operate as biological markers for carcinogenesis and progression and as prognostic biomarkers. Additionally, IGFBP5 has been proved that promotes the invasion and migration of ovarian cancer. Conclusions In general, IGFBPs can serve as predictable biomarkers and potential therapeutic targets for specific tumors. Our results could provide underlying targets for the design of laboratory experiments to elucidate the mechanism of IGFBPs in cancers and identify IGFBP5 as a prognostic factor in ovarian cancers.

Abstract Radiomics is a rapidly evolving field of research that extracts and analyzes quantitative features within medical images. Those features are termed as radiomic features that can characterize a tumor in a comprehensive and quantitative manner with regard to its internal structure and heterogeneity. Radiomic features can be used, alone or in combination with demographic, histological, genomic, or proteomic data, for predicting prognosis or treatment response. Immunotherapy, or immune‐oncology, is the study of cancer treatment by taking advantage of the body's immune system to prevent, control, and eliminate cancer. In this review, we first provide a brief introduction to both radiomics and immune‐oncology in lung cancer. Then, we discuss the need for developing immune‐oncology biomarkers, and the advantages of radiomics in identifying biomarkers related to immunotherapy. We also discuss potential areas in and out of tumors, such as the intra‐tumoral hypoxic region and tumor microenvironment, where radiomic markers might be extracted, as well as a potential application of radiomic biomarkers in clinical lung cancer management. Finally, we present radiation and immune modulation in non‐small cell lung cancer, clinical trials and their design to incorporate radiomic biomarkers, and radiomics‐guided precision radiation therapy.

Abstract A severe voltage sag on the wind‐farm grid side with doubly fed induction generators (DFIGs) can induce a peak inrush current in the rotors and damage converters, resulting in wind‐turbine disconnection from the grid. To prevent this from happening, a variable‐step model predictive control (VS‐MPC) strategy is proposed for improving the wind turbines’ ability to operate without disconnecting themselves from the grid when a fault occurs. First, the predictive‐control state‐space model of a doubly fed wind farm is established according to its working principle. Second, model predictive control (MPC) is applied on the rotor side of the DFIG to realize the rapid tracking of the rotor current to the reference value during low‐voltage ride‐through (LVRT) of the DFIG. Finally, a variable‐step size algorithm is introduced into the MPC controller to change the step size continuously during the LVRT period. This increases the control accuracy, realizing rapid attenuation of each transient component, whereby the wind‐farm LVRT capability is enhanced. The proposed control strategy was simulated and verified using MATLAB/Simulink. The simulation results indicated that VS‐MPC can effectively handle LVRT, allowing the recovery of a wind farm that uses DFIGs and improving the performance of wind‐farm.

Abstract Acquired digestive‐respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large‐scale evidence‐based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive‐respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive‐respiratory tract fistulas. The guidelines conduct an in‐depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Abstract The large‐scale mining of coal resources promotes the formation of section coal pillar groups between working faces. The overlying strata are supported by coal pillars, which leads to the formation of a unique fracture‐bearing structure in the key stratum, resulting in the evolution of fissures (cracks) and a generally high load on the supports. Studying the fracture‐bearing structure formed by coal pillars and overlying strata (fissures) is the basis for realizing rational mining of working faces. Here, the evolution characteristics of coal pillar‐overburden rock (fissures) in shallow coal seam mining and the working resistance of the support with stable fracture bearing structure of section coal pillar and overburden rock were studied in the No. 1‐2 coal mining of Longhua Coal Mine in Shenmu City, Northern Shaanxi. The fissure evolution characteristics on both sides of the coal pillar and the fracture‐bearing structure of the rock stratum were obtained by physical similarity simulation experiment. The mechanical calculation model of the coal pillar‐overburden rock (fissure) structure was established by theoretical derivation and calculation, and the working resistance of advanced support with a stable mechanical structure was studied. The research shows that the fracture evolution and rock fracture characteristics of a shallow coal seam mining face can be divided into three zones. Through the reanalysis of the mechanical structure of coal pillar‐overburden rock (fissure), the combined mechanical structure of the subkey stratum consisting of a lagging broken step rock beam structure and the main key stratum consisting of a hinged rock beam structure was obtained. Combined with the failure characteristics of the section coal pillar, a mechanical structure calculation method suitable for the bearing characteristics of section coal pillar support in shallow coal buried layers was obtained, and the field measurement results were verified.

Abstract The aim of this study was to provide a new effective carrier for rescuing the sensitivity of drug‐resistant in breast cancer cells. Nano‐gold micelles loaded with Dox and Elacridar (FP‐ssD@A‐E) were chemically synthesised. With the increase in the amount of Dox and Elacridar, the encapsulation rate of FP‐ssD@A‐E gradually increased, and the drug loading rate gradually decreased. FP‐ss@A‐E had a sustained‐release effect. Dox, Elacridar, FP‐ss@AuNPs, and FP‐ssD@A‐E significantly improved cell apoptosis, in which, FP‐ssD@A‐E was the most significant. FP‐ssD@A‐E significantly decreased the cell viability and improved the Dox uptake. The levels of VEGFR‐1, P‐gp, IL‐6, and i‐NOS were significantly decreased after Dox, Dox + Elacridar, FP‐ss@AuNPs, and FP‐ssD@A‐E treatment. It was worth noting that FP‐ssD@A‐E had the most significant effects. The prepared FP‐ssD@A‐E micelles, which were spherical in shape, uniform in particle size distribution, and had good drug loading performance and encapsulation efficiency.

Abstract Background TP53 mutations are frequent in non‐small cell lung cancer (NSCLC). Different categories of TP53 mutations may be associated with survival in advanced NSCLC, but their effect on prognosis is diverse. To date, a comprehensive comparison of the relationship between different classes of TP53 alterations and survival in advanced NSCLC has rarely been performed. Moreover, the prognostic significance of a novel approach called the evolutionary action of TP53 (EAp53) in advanced NSCLC is unclear. Methods A total of 210 patients with NSCLC harboring TP53 mutation data were enrolled. Genomic and clinical data for the Memorial Sloan Kettering Cancer Center (MSKCC) cohort with advanced NSCLC were obtained from cBioPortal. Relationship between clinical characteristics and TP53 mutations was performed by Fisher's exact test or χ2 test. Overall survival (OS) analysis was evaluated using Kaplan–Meier method and Cox proportional hazards regression model. Results TP53 mutations were identified in 51.4% of NSCLC patients and were mainly located in exons 5, 7, and 8. The distribution patterns of missense and truncating mutations of TP53 were remarkably different. Among patients with advanced NSCLC who never received immune checkpoint inhibitor treatments, EAp53 high‐risk mutations were significantly associated with poor OS in both our cohort and the MSKCC cohort. Moreover, marked differences were observed in the mutational landscape between patients with EAp53 high‐risk mutations (HR group) and other patients (OT group). The HR group displayed higher mutation frequencies in the RTK, cell cycle, and DNA damage repair (DDR) pathways than the OT group. In addition, the tumor mutation burden in the HR group was significantly higher than that in the OT group. Conclusions This study provided important insights into the molecular‐clinical profile of TP53‐mutated NSCLC patients. Moreover, the data revealed that EAp53 high‐risk mutations were an independent prognostic factor for worse OS in advanced NSCLC.

Abstract The inhomogeneous native oxide shells on the surfaces of III–V group semiconductors typically yield inferior and unstable electrical properties metrics, challenging the development of next‐generation integrated circuits. Herein, the native GaOx shells are profitably utilized by a simple in‐situ thermal annealing process to achieve high‐performance GaSb nanowires (NWs) field‐effect‐transistors (FETs) with excellent bias‐stress stability and synaptic behaviors. By an optimal annealing time of 5 min, the as‐constructed GaSb NW FET demonstrates excellent stability with a minimal shift of transfer curve (ΔVth ≈ 0.54 V) under a 60 min gate bias, which is far more stable than that of pristine GaSb NW FET (ΔVth ≈ 8.2 V). When the high bias‐stress stability NW FET is used as the chargeable‐dielectric free synaptic transistor, the typical synaptic behaviors, such as short‐term plasticity, long‐term plasticity, spike‐time‐dependent plasticity, and reliable learning stability are demonstrated successfully through the voltage tests. The mobile oxygen ion in the native GaOx shell strongly offsets the trapping states and leads to enhanced bias‐stress stability and charge retention capability for synaptic behaviors. This work provides a new way of utilizing the native oxide shell to realize stable FET for chargeable‐dielectric free neuromorphic computing systems.

Manipulating granular materials is a crucial function of robotic grippers. However, the existing approaches always suffer from low efficiency when dealing with large quantities of dispersed granules. To overcome this challenge, inspiration is drawn from an African elephant (Loxodonta Africana), which can employ both fingertip extensions on the trunk tip to efficiently grasp dispersed granular food all at once by mediating state transition of granules. Herein, this bio‐inspired intelligent strategy is integrated into a soft pneumatic gripper for transporting dispersed granules. To evaluate the critical actuation pressures while grasping granules, a library is constructed experimentally, and the effects of the initial relative height and relative lifting speed on the grasping success rate are examined. It is indicated in the experimental results that this trunk‐inspired robotic strategy leads to a success rate of over 90% and saves ≈50% duration of manipulation compared to the individual gripping fashion. Herein, new insights may be offered in this study into a novel manipulation strategy for efficiently transporting dispersed granular materials.

Abstract Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Patient‐derived organoid (PDO) has great potential in precision oncology, but low success rate, time‐consuming culture, and lack of tumor microenvironment (TME) limit its application. Mesenchymal stromal cells (MSC) accumulate in primary site to support tumor growth and recruit immune cells to form TME. Here, MSC and peripheral blood mononuclear cells (PBMC) coculture is used to construct HCC organoid‐on‐a‐chip mimicking original TME and provide a high‐throughput drug‐screening platform to predict outcomes of anti‐HCC immunotherapies. HCC‐PDOs and PBMC are co‐cultured with MSC and Cancer‐associated fibroblasts (CAF). MSC increases success rate of biopsy‐derived PDO culture, accelerates PDO growth, and promotes monocyte survival and differentiation into tumor‐associated macrophages. A multi‐layer microfluidic chip is designed to achieve high‐throughput co‐culture for drug screening. Compared to conventional PDOs, MSC‐PDO‐PBMC and CAF‐PDO‐PBMC models show comparable responses to chemotherapeutic or targeted anti‐tumor drugs but more precise prediction potential in assessing patients’ responses to anti‐PD‐L1 drugs. Moreover, this microfluidic platform shortens PDO growth time and improves dimensional uniformity of organoids. In conclusion, the study successfully constructs microengineered organoid‐on‐a‐chip to mimic TME for high‐throughput drug screening, providing novel platform to predict immunotherapy response of HCC patients.

Abstract Sonodynamic therapy (SDT) has been widely reported as a noninvasive and high‐penetration therapy for cancer; however, the design of an efficient sonosensitizer remains an urgent need. To address this issue, molybdenum disulfide nanoflowers (MoS2 NF) as piezo‐sonosensitizers and introduced sulfur vacancies on the MoS2 NF (Sv‐MoS2 NF) to improve their piezoelectric property for cancer therapy are designed. Under ultrasonic mechanical stress, the Sv‐MoS2 NF resulted in piezoelectric polarization and band tilting, which enhanced the charge carrier separation and migration. This resulted in an improved catalytic reaction for reactive oxygen species (ROS) production, ultimately enhancing the SDT performance. Thanks to the high efficiency of ROS generation, the Sv‐MoS2 NF have demonstrated a good anticancer effect in vitro and in vivo. Following a systematic evaluation, Sv‐MoS2 NF also demonstrated good biocompatibility. This novel piezo‐sonosensitizer and vacancy engineering strategy provides a promising new approach for achieving efficient SDT.

Abstract Objective Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self‐efficacy, self‐injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal‐deprived rhesus monkey animal model, which mimic early adversity in human. Methods Twenty‐five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother‐reared (MR) monkeys and 14 maternally deprived and peer‐reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis. Results The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques. Conclusion This study suggests that early adversity‐induced anxious behaviors are associated with changes in the strength of the amygdala–prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity. Significance Statement This study suggests that early adversity‐induced anxious behaviors are associated with changes in the strength of the amygdala–prefrontal connection. The higher the amygdala–prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala–prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.

Abstract Background Currently there is no standard therapy recommended for second‐line treatment for thymic carcinoma. Our study compared multidrug chemotherapy, single‐agent chemotherapy, and PD‐1 inhibitors in patients diagnosed with advanced thymic carcinoma who had previous platinum‐based chemotherapy at the clinic. Methods The study included patients with thymic carcinoma who failed first‐line platinum‐based chemotherapy. Kaplan–Meier methods were applied in the study for estimating the progression‐free survival (PFS) and overall survival (OS) curves. Pearson chi‐square or Fisher's exact chi‐square test was adopted to make comparisons of the objective response rate (ORR) between treatment groups. Cox regression was used for the multivariate analyses in PFS and OS. Results Among the 92 patients enrolled, multidrug chemotherapy was used in 51 (55.4%) patients for second‐line therapy. Thirty‐six patients (35.9%) received single‐agent chemotherapy, and eight patients (8.7%) underwent PD‐1 inhibitors. The multidrug chemotherapy group showed better efficacy than the other two groups, with an ORR of 35.3% (p = 0.006). The median PFS of multidrug chemotherapy, single‐agent chemotherapy and PD‐1 inhibitors were 5.0 months, 3.0 months, and 4.0 months, respectively (p = 0.008). Patients in the multidrug chemotherapy group also showed an advantage in OS in comparison with the other two treatment groups (p = 0.045), with a median OS of 30.4 months. Multivariate analysis showed that second‐line treatment was independent factor for both PFS (p = 0.035) and OS (p = 0.037). Grade 3–4 AEs were mostly detected in patients receiving multidrug chemotherapy and were primarily hematologic. Treatment‐related mortality was not found in any of the groups. Conclusions Multidrug chemotherapy had a trend toward a more positive response rate and outcomes in longer survival time than single‐agent chemotherapy and PD‐1 inhibitors. Multidrug chemotherapy is a choice worth considering for second‐line therapy in patients with thymic carcinoma if tolerable.