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Abstract Staphylococcal Enterotoxin C2 (SEC2), a classical superantigen, is an antitumor immunotherapy agent. However, the injectable formulation of SEC2 limits its clinical application. Here, it is reported that oral administration of SEC2 activates the intestinal immune system and benefits intestinal health in a mouse model. These results indicate that intact SEC2 is detected in the stomach, intestine, and serum after oral administration. Continuous oral administration of SEC2 activates immune cells in gut‐associated lymphoid tissues, promoting extensive differentiation and proliferation of CD4+ and CD8+ T cells and CD19+ B cells, leading to increased production of cytokines and secretory immunoglobulin A. SEC2 also enhances intestinal barrier function, as demonstrated by an increased villus length/crypt depth ratio and elevated expression of mucins and tight junction proteins. Additionally, SEC2 indirectly influenced gut microbiota, reinforcing potential probiotics and short‐chain fatty acid synthesis. Enhanced differentiation of T and B cells in the spleen, coupled with elevated serum interleukin‐2 levels, suggests systemic immune enhancement following oral administration of SEC2. These findings provide a scientific basis for the development of SEC2 as an oral immunostimulant for immune enhancement and anti‐tumor immunotherapy.

Abstract The quest for mechanoluminescence (ML) in zinc sulfide (ZnS) spans more than a century, initially sparked by observations of natural minerals. There has been a resurgence in research into ML materials in recent decades, driven by advances in optoelectronic technologies and a deeper understanding of their luminescent properties under mechanical stress. ZnS, in particular, has garnered attention owing to its remarkable ability to sustain luminescence after more than 100,000 mechanical stimulations, positioning it as a standout candidate for optoelectronic applications. In contrast to conventional photoluminescent and electroluminescent light sources, ZnS composite elastomers have emerged as flexible, stretchable self‐powered light sources with considerable practical implications. This review introduces the development history, ML mechanisms, prototype ML devices, ZnS‐based ML material preparation methods, and their diverse applications spanning environmental mechanical‐to‐optical energy conversion, E‐signatures, anti‐counterfeiting, wearable information sensing devices, advanced battery‐free displays, biomedical imaging, and optical fiber sensors for human–computer interactions, among others. By integrating insights from ML‐optics, mechanics, and flexible optoelectronics, and by summarizing pertinent perspectives on current scientific challenges, application technology hurdles, and potential solutions for emerging scientific frontiers, this review aims to furnish fundamental guidance and conceptual frameworks for the design, advancement, and cutting‐edge application of novel mechanoluminescent materials.

Abstract Background Germline mutations have been identified in a small number of hereditary cancers, but the genetic predisposition for many familial cancers remains to be elucidated. Methods This study identified a Chinese pedigree that presented different cancers (breast cancer, BRCA; adenocarcinoma of the esophagogastric junction, AEG; and B‐cell acute lymphoblastic leukemia, B‐ALL) in each of the three generations. Whole‐genome sequencing and whole‐exome sequencing were performed on peripheral blood or bone marrow and cancer biopsy samples. Whole‐genome bisulfite sequencing was conducted on the monozygotic twin brothers, one of whom developed B‐ALL. Results According to the ACMG guidelines, bioinformatic analysis of the genome sequencing revealed 20 germline mutations, particularly mutations in the DNAH11 (c.9463G > A) and CFH (c.2314G > A) genes that were documented in the COSMIC database and validated by Sanger sequencing. Forty‐one common somatic mutated genes were identified in the cancer samples, displaying the same type of single nucleotide substitution Signature 5. Meanwhile, hypomethylation of PLEK2, MRAS, and RXRA as well as hypermethylation of CpG island associated with WT1 was shown in the twin with B‐ALL. Conclusions These findings reveal genomic alterations in a pedigree with multiple cancers. Mutations found in the DNAH11, CFH genes, and other genes predispose to malignancies in this family. Dysregulated methylation of WT1, PLEK2, MRAS, and RXRA in the twin with B‐ALL increases cancer susceptibility. The similarity of the somatic genetic changes among the three cancers indicates a hereditary impact on the pedigree. These familial cancers with germline and somatic mutations, as well as epigenomic alterations, represent a common molecular basis for many multiple cancer pedigrees.

ABSTRACT Background The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan‐cancers. Methods Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross‐validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. Results A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36–62.65 months). In the training cohort of 1425 patients, through Lasso regression cross‐validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C‐indexes of the model for predicting 1‐, 3‐, 5‐, and 10‐year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723–8.397; log‐rank p

Abstract The silicon carbide (SiC) crystal growth is a multiple‐phase aggregation process of Si and C atoms. With the development of the clean energy industry, the 4H‐SiC has gained increasing attention as it is an ideal material for new energy automobiles and optoelectronic devices. The aggregation process is normally complex and dynamic due to its distinctive formation energy, and it is hard to study and trace back in a non‐destructive and comprehensive way. Here, this work developed a non‐destructive and deep learning‐enhanced characterization method of 4H‐SiC material, which was based on micro‐CT scanning, the verification of various optical measurements, and the convolutional neural network (ResNet‐50 architecture). Harmful defects at the micro‐level, polytypes, micropipes, and carbon inclusions could be identified and orientated with more than 96% high performance on both accuracy and precision. The three‐dimensional visual reconstruction with quantitative analyses provided a vivid tracing back of the SiC aggregation process. This work demonstrated a useful tool to understand and optimize the SiC growth technology and further enhance productivity.

Abstract Field application of beef cattle feedlot runoff may transport manure‐borne microbes and antibiotic resistant bacteria to agricultural soils eventually impacting deeper soils and groundwater. To evaluate this potential, total soil, antibiotic resistance (AR), and fecal indicator bacteria (Escherichia coli and Enterococcus) and the presence/abundance of AR genes were examined to a depth of 1.8 m in an agricultural field receiving long‐term application of feedlot runoff and compared to a nearby pasture receiving no runoff. While plate counts of total soil bacteria and cefotaxime‐resistant, erythromycin‐resistant, and tetracycline‐resistant bacteria decreased with depth on both fields (p

Abstract In this study, an observation points‐based positive‐unlabeled learning algorithm (hence called OP‐PUL) is proposed to deal with positive‐unlabeled learning (PUL) tasks by judiciously assigning highly credible labels to unlabeled samples. The proposed OP‐PUL algorithm has three components. First, an observation point classifier ensemble (OPCE) algorithm is constructed to divide unlabeled samples into two categories, which are temporary positive and permanent negative samples. Second, a temporary OPC (TOPC) is trained based on the combination of original positive samples and permanent negative samples and then the permanent positive samples that are correctly classified with TOPC are retained from the temporary positive samples. Third, a permanent OPC (POPC) is finally trained based on the combination of original positive samples, permanent positive samples and permanent negative samples. An exhaustive experimental evaluation is conducted to validate the feasibility, rationality and effectiveness of the OP‐PUL algorithm, using 30 benchmark PU data sets. Results show that (1) the OP‐PUL algorithm is stable and robust as unlabeled samples and positive samples are increased in unlabeled data sets and (2) the permanent positive samples have a consistent probability distribution with the original positive samples. Moreover, a statistical analysis reveals that POPC in the OP‐PUL algorithm can yield better PUL performances on the 30 data sets in comparison with four well‐known PUL algorithms. This demonstrates that OP‐PUL is a viable algorithm to deal with PUL tasks.

Abstract Immunotherapy targeting PD‐L1 is still ineffective for a wide variety of tumors with high unpredictability. Deploying combined immunotherapy with alternative targeting is practical to overcome this therapeutic resistance. Here, the deficiency of serine‐threonine kinase STK24 is observed in tumor cells causing substantial attenuation of tumor growth in murine syngeneic models, a process relying on cytotoxic CD8+ T and NK cells. Mechanistically, STK24 in tumor cells associates with and directly phosphorylates AKT at Thr21, which promotes AKT activation and subsequent PD‐L1 induction. Deletion or inhibition of STK24, by contrast, blocks IFN‐γ‐mediated PD‐L1 expression. Various murine models indicate that in vivo silencing of STK24 can significantly enhance the efficacy of the anti‐PD‐1 blockade strategy. Elevated STK24 levels are observed in patient specimens in multiple tumor types and inversely correlated with intratumoral infiltration of cytotoxic CD8+ T cells and with patient survival. The study collectively identifies STK24 as a critical modulator of antitumor immunity, which engages in AKT and PD‐L1/PD‐1 signaling and is a promising target for combined immunotherapy.

Abstract Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post‐surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti‐recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti‐recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.

Abstract Mechanoluminescence is a smart light‐emitting phenomenon in which applied mechanical energy is directly converted into photon emissions. In particular, mechanoluminescent materials have shown considerable potential for applications in the fields of energy and sensing. This study thoroughly investigates the mechanoluminescence and long afterglow properties of singly doped and codoped Sr2MgSi2O7(SMSO) with varying concentrations of Eu2+ and Dy3+ ions. Subsequently, a comprehensive analysis of its multimode luminescence properties, including photoluminescence, mechanoluminescence, long afterglow, and X‐ray‐induced luminescence, is conducted. In addition, the density of states mapping is acquired through first‐principles calculations, confirming that the enhanced mechanoluminescence properties of SMSO primarily stem from the deep trap introduced by Dy3+. In contrast to traditional mixing with Polydimethylsiloxane, in this study, the powders are incorporated into optically transparent wood to produce a multiresponse with mechanoluminescence, long afterglow, and X‐ray‐excited luminescence. This structure is achieved by pretreating natural wood, eliminating lignin, and subsequently modifying the wood to overall modification using various smart phosphors and epoxy resin composites. After natural drying, a multifunctional composite wood structure with diverse luminescence properties is obtained. Owing to its environmental friendliness, sustainability, self‐power, and cost‐effectiveness, this smart mechanoluminescence wood is anticipated to find extensive applications in construction materials and energy‐efficient displays.

Abstract Background Primary focal hyperhidrosis (PFH) is an autonomic neurological disease in which exocrine glands are oversecreted due to autonomic dysfunction of the sympathetic nervous system. Chrna1 promotes the pathogenesis of PFH. We aimed to check if downregulating of Chrna1 by cisatracurium could alleviate the symptoms of PFH. Methods The effect of cisatracurium in a hyperhidrosis mice model induced by pilocarpine hydrochloride was monitored for sweat gland secretion, and ultrastructural sweat secretory granules in sweat glands were analyzed. Meanwhile, markers of hyperhidrosis were checked, and release of Bdnf and Nrg1 from sympathetic ganglia axon was tested. Furthermore, the mechanism of cisatracurium function was evaluated in vitro using HEK293 expressing Chrna1. Finally, the effect of cisatracurium was determined in the hyperhidrosis mice model with overexpression or downregulation of Chrna1. Results In hyperhidrosis mice, pretreatment with cisatracurium effectively inhibited sweat secretion, along with fewer particle secretion in sweat glands. The molecular markers of hyperhidrosis (Aqp5 and Cacna1c) were inhibited by cisatracurium, acetylcholine (Ach) level in serum was found decreased. Neurotrophic factors (Bdnf and Nrg1) secreted by sympathetic axon activation were also inhibited. At last, it was confirmed that cisatracurium could not alter the gene or protein expression level of Chrna1, but could block the ion channel. Overexpression of Chrna1 abolished the effect of cisatracurium on hyperhidrosis, while cisatracurium could not function more in siChrna1‐treated mice. Conclusion Our results suggested that pretreatment of cisatracurium could alleviate hyperhidrosis in mice, probably through blocking the ion channel function of Chrna1.

Abstract Background The aim of this network meta‐analysis (NMA) was to evaluate the efficacy and safety of PD‐1/PD‐L1 inhibitors, alone or in combination with chemotherapy, as first‐line treatment for wild‐type advanced non‐small cell lung cancer. Methods We systematically searched databases, Clinical Trial.gov and included randomized clinical trials focusing on advanced NSCLC using PD‐1/PD‐L1 inhibitors as first‐line treatment. Hazard ratio for overall survival and progression‐free survival, odds ratio for any‐cause high‐adverse events (grade 3 or higher) were documented according to Bayesian NMA. Subgroup analysis was performed according to PD‐L1 level and histology. Results Thirteen trials including 9154 patients were included. In the PD‐L1 nonselective cohort, chemotherapy in combination with pembrolizumab and atezolizumab, respectively, were significantly better than any other treatment strategies in both OS benefit (HR = 0.63; HR = 0.85) and PFS benefit (HR = 0.52; HR = 0.63). In subgroup analysis, pembrolizumab appeared to provide the best OS benefit (HR = 0.67) as well as the best PFS benefit (HR = 0.67) in the PD‐L1 ≥ 50% cohort. In contrast, pembrolizumab combined with chemotherapy exhibited the best OS benefit in the PD‐L1

Abstract Background The aim of this study was to estimate the efficacy and safety of bevacizumab combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in advanced non‐small cell lung cancer (NSCLC) patients. Methods We searched randomized controlled trials (RCTs) on bevacizumab combined with EGFR TKIs in the NSCLC Cochrane Library, Web of Science, PubMed and Embase. The data were extracted and assessed according to the Cochrane Handbook. We calculated the hazard ratio (HR), risk ratio (RR), and confidence interval (CI), and accomplished this meta‐analysis with Stata 14 software. Results Of 1301 articles scanned, five articles were involved in this meta‐analysis. We determined that compared with using EGFR TKIs alone, combination treatment significantly prolongs progression‐free survival (PFS) (HR = 0.61, 95% CI = 0.52–0.70; p

Abstract Inflammatory bowel disease (IBD) is characterized by recurring inflammatory disorders in digestive system, and devoid of effective treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9), stimulated via inflammation whose inhibition could decrease secretion of inflammatory factors. We then determined whether inhibition of PCSK9 could improve the inflammation. First, rats model of colitis was first established via administration of 2,4,6‐trinitrobenzenesulfonic acid (TNBS), and then verified via determination of body weight loss, myeloperoxidase (MPO) activity, and histopathological analysis of colonic damage. Results showed that treatment with TNBS induced a great body weight loss, MPO activity increase, and serious colonic damage, showing an obviously character of IBD. PCSK9 was elevated in TNBS‐induced rats, and PCSK9 inhibition delivered by adenovirus vector increased the body weight, decreased MPO activity, and ameliorated histological change of colon. Second, the protective effect of PCSK9 inhibition against TNBS‐induced colitis was accompanied by decrease of proinflammatory factors secretion, including tumor necrosis factor‐α, interleukin‐1β, interleukin‐6, intercellular adhesion molecule 1, and monocyte chemoattractant protein‐1. TNBS could activate toll‐like receptor 4 (TLR4)/nuclear factor‐kappa B (NF‐κB) signaling pathway, while PCSK9 inhibition suppressed activation of TLR4/NF‐κB in TNBS‐induced rats. In conclusion, PCSK9 inhibition attenuated TNBS‐induced rat colitis through anti‐inflammatory effect under inactivation of TLR4/NF‐κB, suggesting potential therapeutic strategy in IBD.

In order to comprehensively analyze the dynamic response of full-depth asphalt pavement under moving load, a three-dimensional model of pavement structure and dynamic load moving zone are established based on ABAQUS finite element software. Based on the time history curves of different structures, the stress-strain states at the bottom of each structural layer in different structures under moving load are analyzed. The results show that the stress, strain, and shear stress of the middle layer of full-depth pavement are smaller than those of semirigid base pavement, and rutting is closely related to the deformation of this layer. The dynamic response results of the same structure at different speeds are similar, but the increase of the maximum speed will increase the shear stress at the bottom of the layer, and the road is more prone to longitudinal crack.

In the terminal guidance phase of intercepting aerial target, a guidance law, satisfying impact angle constraint, acceleration constraint, and second-order dynamic characteristic of interceptor autopilot, is designed based on the prescribed performance control and dynamic surface control method. Firstly, a two-dimensional plane interception model considering the dynamic characteristics of autopilot and input constraints is established. Furthermore, for the nonconstrained system, based on the dynamic surface control, the prescribed performance reaching law is used to ensure that the line-of-sight angle and the line-of-sight angle rate can converge to the prescribed range in finite time. At the same time, an adaptive law is used to estimate the uncertainty caused by target maneuver and autopilot. Then, aiming at the acceleration constraint, an auxiliary system is established to convert the restricted system into a nonrestricted system. The finite-time convergence of the terminal line-of-sight tracking error, the line-of-sight rate, and the uniform ultimate boundedness of the system are rigorously proved by Lyapunov stability theory. Finally, the simulation results show that the proposed guidance law can make the interceptor have better interception performance when attacking targets with different maneuvering forms.

The iASSIST navigation system is a handheld accelerometer‐based navigation system that has been applied in clinical practice in recent five years. This meta‐analysis aimed to compare the radiographic and clinical outcomes of iASSIST navigation with conventional surgical techniques for patients undergoing total knee arthroplasty (TKA) and to compare the surgery time between an iASSIST group and a conventional treatment group. This systematic review and meta‐analysis included all comparative prospective and retrospective studies published in Pubmed, Embase, the Cochrane Central Register of Controlled Trials, the Web of Science and the CNKI databases over the past 20 years. Inclusion criteria were studies that compared the iASSIST navigation system with conventional TKA. The primary outcomes were mechanical axis (MA) and outliers, which means postoperative MA varus or valgus of more than 3°. Secondary outcomes were coronal femoral angle (CFA) and coronal tibial angle (CTA). Knee Society Score (KSS) was used to evaluate functional outcome. The Newcastle–Ottawa Scale (NOS) was used to assess the methodological quality of included studies. Eight studies involving 558 knees were included in this meta‐analysis. Of these, 275 patients used the iASSIST navigation system and 283 used conventional surgical techniques. A total of 5 studies were considered high quality and the other 3 were considered to be of moderate quality. The occurrence of malalignment of >3° in the iASSIST group was 13.3%, compared with 29.04% in the conventional group. Postoperative MA of the iASSIST group was significantly better than that of the conventional group (I2 = 19%, OR = −0.92, 95% CI = −1.09 to −0.75, P

Abstract Multivesicular bodies (MVBs) fuse with not only the plasma membranes to release extracellular vesicles (EVs) but also lysosomes for degradation. Rab7 participates in the lysosomal targeting of MVBs. However, the proteins on MVB that directly bind Rab7, causing MVB recruitment of Rab7 remain unidentified. Here, we show that Coro1a undergoes neddylation modification at K233 by TRIM4. Neddylated Coro1a is associated with the MVB membrane and facilitates MVB recruitment and activation of Rab7 by directly binding Rab7. Subsequently, MVBs are targeted to lysosomes for degradation in a Rab7‐dependent manner, leading to reduced EV secretion. Furthermore, a decrease in neddylated Coro1a enhances the production of tumour EVs, thereby promoting tumour progression, indicating that neddylated Coro1a is an ideal target for the regulation of EV biogenesis. Altogether, our data identify a novel substrate of neddylation and reveal an unknown mechanism for MVB recruitment of Rab7, thus providing new insight into the regulation of EV biogenesis.

Objectives The arthroscopic “lateral gutter drive‐through” (LGDT) sign is reported to diagnose popliteus tendon (PT) injury with high sensitivity and specificity. However, no study has provided a postoperative evaluation of combined posterior cruciate ligament (PCL) and posterolateral corner (PLC) injuries using the LGDT test. Methods From January 2012 to January 2015, a total of 80 consecutive patients who underwent combined PCL reconstruction and PLC surgeries were identified. Fifty eligible patients were included in this study for evaluation with subjective scoring systems, physical examinations, posterior and varus stress radiographs, and second‐look arthroscopic surgeries during hardware removal operation. Results Forty‐nine patients were available for a mean of 31.5 ± 9.3 months follow‐up (range, 24.0–81.0 months). In terms of PLC injury pattern, there were 27 type A, 10 type B, and 12 type C patients, with 21 acute cases and 28 chronic cases. At the final follow‐up, subjective scores were all significantly improved. The side‐to‐side difference (SSD) of posterior tibial translation (PTT) improved from 18.4 ± 9.2 mm (range, 12.9–25.6 mm) to 5.2 ± 5.0 mm (range, −5.0−18.5 mm, P

Abstract Background Thus far, the incidence, mortality, and temporal trend data of oropharyngeal cancers (OPC) in China were few. We estimated the incidence, mortality, and temporal patterns of OPC in China during 2008–2012 according to the data from 135 population-based cancer registries to better understand the epidemiological pattern of OPC and to provide more precise information for OPC control in China. Methods According to the data of diagnosed OPC reported to 135 cancer registries during 2008–2012, we calculated age-standardized rate of incidence and mortality by 2000 Chinese standard population (ASRIC and ASRMC) and by 1985 Segi’s world standard population (ASRIW and ASRMW) by age, sex, and geographic regions; annual percentage changes of OPC incidence and mortality were calculated using Joinpoint trend analysis. Results ASRIW and ASRMW were 2.22/100,000 person-years and 0.94/100,000 person-years, respectively. The incidence and mortality in urban areas were higher than those in rural areas. ASRIC and ASRIW of males were higher than those of females. The overall ASRIC of OPC was significantly increased by 6.2% annually between 2003 and 2006 (P = 0.038), but remained stable between 2007 and 2012 (P = 0.392). ASRIC and ASRMC of males and in rural areas were significantly increased in the last decade (P 0.05). Conclusions Across multiple cancer registries in China, there was an obvious increase in OPC in the recent decade, especially for incidence and mortality of males and in rural areas, whereas the rates of females remained stable. A healthy lifestyle should be advocated and early diagnosis and early treatment of OPC should be enhanced.