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Abstract Background For patients with advanced non‐small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death‐1 (PD‐1)/cytotoxic T lymphocyte‐associated antigen‐4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti‐PD‐1/PD‐L1 antibodies. Methods We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab‐based regimens in later therapy lines. Results A total of 41 advanced NSCLC patients refractory to anti‐PD‐1/PD‐L1 therapy were enrolled. More than half of the patients received cadonilimab‐based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression‐free survival for all evaluated patients was 108.0 days. Due to the short follow‐up period, the median overall survival has not yet been reached. Treatment‐related adverse events (TRAEs) and immune‐related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma‐glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. Conclusions In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab‐based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti‐PD‐1/PD‐L1 therapy.

Abstract In the realm of experimental and epidemiological research, the impact of endotoxemia caused by obesity on male fertility is widely acknowledged. However, the existing body of evidence lacks rigorous studies to substantiate this notion. To address this gap, we have selected protocatechuic acid (PCA) as a potential inhibitor of endotoxemia induced by obesity. This selection is further supported by our utilization of a male model of C57BL/6J mice induced by a high‐fat diet (HFD) and the fecal microbiota transplantation assay. Our findings reveal a negative correlation between semen quality and endotoxin levels in the mice model induced by an HFD. Furthermore, intervention with PCA resulted in the restoration of testicular morphology, sperm traits, and function. The transplantation of PCA did not exhibit restorative effects on semen quality, but it did effectively prevent obesity‐induced intestinal leakage and endotoxemia. By directly enhancing antioxidant capacity, PCA successfully reversed the fertility reduction caused by obesity. These findings offer substantiation that endotoxemia does not play a significant role in the diminished fertility observed in obese males and propose that the inclusion of dietary antioxidant supplementation can potentially restore male fertility.

Abstract For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour‐associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy‐sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC‐XENA, GEO and TISCH databases were extracted for analysis. Based on both single‐cell datasets and bulk transcriptome profiles, a macrophage‐related score (MRS) consisting of the 10‐gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial‐mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high‐MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E‐knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.

Abstract Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal radiotherapy regimen, particularly in terms of total dose and planned range of irradiation field, remains unclear. This phase III clinical trial aimed to compare the survival benefits between different radiation doses and different target fields. Methods This trial compared two aspects of radiation treatment, total dose and field, using a two‐by‐two factorial design. The high‐dose (HD) group received 59.4 Gy radiation, and the standard‐dose (SD) group received 50.4 Gy. The involved field irradiation (IFI) group and elective nodal irradiation (ENI) group adopted different irradiation ranges. The participants were assigned to one of the four groups (HD+ENI, HD+IFI, SD+ENI and SD+IFI). The primary endpoint was overall survival (OS), and the secondary endpoints included progression‐free survival (PFS). The synergy indexwas used to measure the interaction effect between dose and field. Results The interaction analysis did not reveal significant synergistic effects between the dose and irradiation field. In comparison to the target field, patients in IFI or ENI showed similar OS (hazard ratio [HR] = 0.99, 95% CI: 0.80‐1.23, p = 0.930) and PFS (HR = 1.02, 95% CI: 0.82–1.25). The HD treatment did not show significantly prolonged OS compared with SD (HR = 0.90, 95% CI: 0.72–1.11, p = 0.318), but it suggested improved PFS (25.2 months to 18.0 months). Among the four groups, the HD+IFI group presented the best survival, while the SD+IFI group had the worst prognosis. No significant difference in the occurrence of severe adverse events was found in dose or field comparisons. Conclusions IFI demonstrated similar treatment efficacy to ENI in CCRT of ESCC. The HD demonstrated improved PFS, but did not significantly improve OS. The dose escalation based on IFI (HD+IFI) showed better therapeutic efficacy than the current recommendation (SD+ENI) and is worth further validation.

Objective It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure. Methods We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed. Results All six patients were followed up for 24 to 46 months (mean follow‐up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection‐related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation. Conclusion Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long‐term disease‐free survival with acceptable complications and satisfying neurological function.

Abstract Left ventricular assist device (LVAD) implantation is an effective alternative treatment to heart transplantation, especially for end‐stage heart failure patients who are ineligible for or unable to await a heart transplant. This report describes a complex and innovative surgery where LVAD implantation was performed alongside multiple concomitant cardiac and aortic procedures. A 62‐year‐old male patient with complicated comorbidities developed acute myocardial infarction and subsequent refractory advanced heart failure. Given his critically ill condition and intractable anatomical malformations, the CH‐VAD left ventricular assist system implantation was performed concomitantly with the Bentall procedure, coronary artery bypass grafting, tricuspid valvuloplasty, and foramen ovale closure. The patient was successfully discharged. This case details the medical decision‐making process and surgical strategy and demonstrates the feasibility of LVAD implantation combined with multiple additional cardiac and aortic procedures in expert cardiac centres. Success relies on experienced cardiac surgeons and a multidisciplinary LVAD Heart Team, ensuring excellence in surgical techniques, preoperative evaluation, post‐operative care, and rehabilitation.

Abstract The development of coalbed methane (CBM) in China is susceptible to the influence of microstructure. Therefore, it is crucial to understand the extension laws of hydraulic fractures and engineering responses in coal reservoirs affected by microstructure development. Utilizing the Dahebian block in western Guizhou as the study area, this investigation examines the coal reservoir characteristics, fracturing, and drainage engineering analysis of the well DC1 group in the region. The aim is to discuss the spatial distribution characteristics of hydraulic fractures, geological controlling factors influenced by microstructure, and their corresponding engineering responses. The results indicate that, for coal reservoirs unaffected by microstructure, the extension laws of the fracture network in both longitudinal and planar directions are influenced by burial depth and the regional stress field. In the microstructural belt, tectonic stress dominates, causing changes in the ground stress field. Consequently, the hydraulic fracture network deviates from the direction of the maximum principal stress during the extension process. When a secondary fracture is nearby, the hydraulic fracture network extends towards the shortest path radial secondary fracture direction, leading to a rapid increase in fracture width per unit length until it intersects with the secondary fracture. Additionally, the presence of secondary joints near the microfault structure decreases fracturing pressure and results in a dense distribution of the fracture network. This promotes the formation of a complex fracture network, favorable for fracturing. The extension of the fracture network in complex structural development areas is influenced by the microfault structure between wells, which is reflected in the fracturing construction pressure and fluid output. This accounts for the significant variations in the early drainage performance of CBM wells.

ABSTRACT Background Lung squamous cell carcinoma (LUSC) is a type of lung cancer that develops in the squamous cells. It is known to be promoted by the activation of various signaling pathways and the dysregulation of key regulatory molecules. One such molecule, 5′‐nucleotidase domain containing 2 (NT5DC2), has been identified as a critical regulator in various cancers including lung cancer. However, there are no data regarding its role in LUSC. Methods The mRNA expression of insulin‐like growth factor 2 mRNA–binding protein 3 (IGF2BP3), CCCTC‐binding factor (CTCF), and NT5DC2 was analyzed using quantitative real‐time polymerase chain reaction (qRT‐PCR), whereas their protein expression was assessed using a western blotting assay. Cell proliferation was determined using a cell counting kit‐8 (CCK‐8) assay. Cell apoptosis, CD11b expression, and CD206 expression were analyzed using flow cytometry. Tube formation was assessed through a tube formation assay. Glucose consumption, lactate production, and ATP levels were measured using colorimetric methods. The effect of NT5DC2 on the malignant progression of LUSC cells was analyzed using a xenograft mouse model assay. The levels of transforming growth factor‐beta 1 (TGF‐β1) and interleukin‐10 (IL‐10) were detected using enzyme‐linked immunosorbent assays. The associations among IGF2BP3, CTCF and NT5DC2 were identified using dual‐luciferase reporter assay, RNA immunoprecipitation assay and m6A RNA immunoprecipitation assay. Results The expression of NT5DC2 was found to be upregulated in LUSC tissues and cells when compared with normal lung tissues and normal human bronchial epithelial cells. Silencing of NT5DC2 inhibited LUSC cell proliferation, tube formation, glycolysis, M2 macrophage polarization, and tumor formation while inducing cell apoptosis. In addition, CTCF was found to transcriptionally activate NT5DC2 in LUSC cells. IGF2BP3 stabilized the mRNA expression of CTCF through m6A methylation. Further, overexpression of CTCF or NT5DC2 attenuated the effects of IGF2BP3 silencing in both NCI‐520 and SK‐MES‐1 cells. Conclusion The IGF2BP3/CTCF axis–dependent NT5DC2 promotes M2 macrophage polarization, thereby enhancing the malignant progression of LUSC. This study was the first to reveal the role of NT5DC2 in LUSC and the underlying mechanism. The result suggests that targeting the IGF2BP3/CTCF/NT5DC2 axis may have clinical significance in the treatment of LUSC.

Abstract Optical metasurfaces with pronounced spectral characteristics are promising for sensor applications. Currently, deep learning (DL) offers a rapid manner to design various metasurfaces. However, conventional DL models are usually assumed as black boxes, which is difficult to explain how a DL model learns physical features, and they usually predict optical responses of metasurfaces in a fuzzy way. This makes them incapable of capturing critical spectral features precisely, such as high quality (Q) resonances, and hinders their use in designing metasurface sensors. Here, a transformer‐based explainable DL model named Metaformer for the high‐intelligence design, which adopts a spectrum‐splitting scheme to elevate 99% prediction accuracy through reducing 99% training parameters, is established. Based on the Metaformer, all‐dielectric metasurfaces based on quasi‐bound states in the continuum (Q‐BIC) for high‐performance metasensing are designed, and fabrication experiments are guided potently. The explainable learning relies on spectral position encoding and multi‐head attention of meta‐optics features, which overwhelms traditional black‐box models dramatically. The meta‐attention mechanism provides deep physics insights on metasurface sensors, and will inspire more powerful DL design applications on other optical devices.

Abstract Silicon Carbide (SiC) Gate Turn‐off (GTO) thyristor is regarded as a promising option for pulsed power applications; however, the formation of high di/dt has been constrained by the slow current rise transient phase and the turn‐on current heterogeneity over the chip device. In this paper, a practical integrated multi‐cell simulation is performed to physically characterize the turn‐on transient of SiC GTO thyristor. Through examining electrical coupling between adjacent cells caused by both parasitics of electrode metallization and carrier travelling via SiC, the current distributions are observed, and the carrier transport dynamics are analyzed in detail. Furthermore, physical mechanisms dominating the current heterogeneity among multi‐cells are discovered in depth. It is revealed that the current heterogeneity during the turn‐on transient is primarily resulted from the Gate signal delay caused by the Gate Runner metallization, and the lateral interaction from adjacent semiconductor regions adds to this inhomogeneity; however, this situation can be improved once the electrical distance between each Anode contact and the Anode electrode gets lowered. Design method for turn‐on performance improvement is also proposed accordingly. Besides, based on the analysis conducted on the multi‐cell simulation results, the possible reason of the extremely slow current rise transient phase is speculated and experimentally verified. The improvement in the comprehension of SiC GTO's turn‐on transient, which cannot be obtained from the traditional investigation from the viewpoint of one elementary cell, will provide guiding principles helping in directing future efforts to advance the improvement of device design technology.

Abstract Objective To assess the impact of the IFIT3/TBK1 signalling pathway in activating plasmacytoid dendritic cells (pDCs) and its role in the development of SSc. Methods Utilized single‐cell RNA sequencing (scRNA‐seq) and high‐throughput transcriptome RNA sequencing to reveal the differential abundance of pDCs and the role of the key gene IFIT3 in SSc. Conducted in vitro cell experiments to evaluate the effect of IFIT3/TBK1 signalling pathway intervention on pDC activation cytokine release and fibroblast function. Constructed an IFIT3−/− mouse model using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) gene editing to assess the potential benefits of intervening in the IFIT3/TBK1 signalling pathway on skin and lung fibrosis in the SSc mouse model. Results The IFIT3/TBK1 signalling pathway plays a crucial role in activating pDCs, with IFIT3 acting as an upstream regulator of TBK1. Intervention in the IFIT3/TBK1 signalling pathway can inhibit pDC activation cytokine release and impact fibroblast function. The IFIT3−/− mouse model shows potential benefits of targeting the IFIT3/TBK1 signalling pathway in reducing skin and lung fibrosis in the SSc mouse model. Conclusion This study provides new insights into potential therapeutic targets for SSc, highlighting the critical role of the IFIT3/TBK1 signalling pathway in SSc development. Highlights This study elucidates the pivotal role of plasmacytoid dendritic cells (pDCs) in systemic sclerosis (SSc). This study identified the key regulatory gene involved in systemic sclerosis (SSc) as IFIT3. This study has found that IFIT3 functions as an upstream regulatory factor, activating TBK1. This study provides Evidence of the regulatory effects of the IFIT3/TBK1 pathway on plasmacytoid dendritic cells (pDCs). This study validated the therapeutic potential using the IFIT3−/− mouse model.

Abstract The development of the electric vehicle industry has spurred demand for secondary batteries capable of rapid‐charging and slow‐discharging. Among them, sodium‐ion batteries (SIBs) with layered oxide as the cathode exhibit competitive advantages due to their comprehensive electrochemical performance. However, to meet the requirements of rapid‐charging and slow‐discharging scenarios, it is necessary to further enhance the rate performance of the cathode material to achieve symmetrical capacity at different rates. Simultaneously, minimizing lattice strain during asymmetric electrochemical processes is also significant in alleviating strain accumulation. In this study, the ordered distribution of transition metal layers and the diffusion pathway of sodium ions are optimized through targeted K‐doping of sodium layers, leading to a reduction of the diffusion barrier and endowment of prominent rate performance. At a 20C rate, the capacity of the cathode can reach 94% of that at a 0.1C rate. Additionally, the rivet effect of the sodium layers resulted in a global volume strain of only 0.03% for the modified cathode during charging at a 10C rate and discharging at a 1C rate. In summary, high‐performance SIBs, with promising prospects for rapid‐charging and slow‐discharging capability, are obtained through the regulation of sodium layers, opening up new avenues for commercial applications.

Abstract In this article, a modified scheme of the fast dipole method (FDM) is proposed based on the Cartesian tensor. To achieve separation between the field and the source, the Taylor series used in the FDM is an incomplete second‐order expansion, which limits computational accuracy and flexibility. To address this issue, a Cartesian tensor is employed to expand the interactions between the far‐group pairs. This approach allows for a complete expansion of any order and offers flexibility in precision control, enabling a balance between computational efficiency and accuracy requirements across different application scenarios. Moreover, the computational accuracy of the proposed method can be improved without a substantial increase in time and memory requirements compared to the FDM. The validity and accuracy of the proposed method are demonstrated with numerical examples.

Key Clinical Message This case illustrates the clinical heterogeneity of porokeratosis (PK), with a patient presenting with both disseminated superficial actinic PK‐like facial lesions and PK of Mibelli‐like lesions on the buttocks and lower limbs. Ultraviolet exposure, infection, and immunosuppression may contribute to the manifestation of multiple clinical forms in a single patient. Close monitoring for potential malignant transformation is essential, particularly in elderly patients with long disease duration and a history of oncological conditions.

Abstract In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient‐derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function‐associated single‐cell RNA sequencing (FascRNA‐seq) platform allowing both phenotypic evaluation and scRNA‐seq at single‐organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA‐seq data of individual pLCOs with their responses to anti‐PD‐1 (αPD‐1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti‐tumor immunity, to identify potential tumor‐reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA‐seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.

Abstract To tackle misdiagnosis in lung cancer screening with low‐dose computed tomography (LDCT), we aimed to compile a genome atlas for differentiating benign, preinvasive, and invasive lung nodules and characterize their molecular pathogenesis. We collected 432 lung nodule tissue samples from Chinese patients, spanning benign, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA). We performed comprehensive sequencing, examining somatic variants, gene expressions, and methylation levels. Our findings uncovered EGFR and TP53 mutations as key drivers in ‐ early lung cancer development, with EGFR mutation frequency increasing with disease progression. Both EGFR mutations and EGF/EGFR hypo‐methylation activated the EGFR pathway, fueling cancer growth. Transcriptome analysis identified four lung nodule subtypes (G1‐4) with distinct molecular features and immune cell infiltrations: EGFR‐driven G1, EGFR/TP53 co‐mutation G2, inflamed G3, stem‐like G4. Estrogen/androgen response was associated with the EGFR pathway, proposing a new therapy combining tyrosine kinase inhibitors with antiestrogens. Preinvasive nodules exhibited stem cell pathway enrichment, potentially hindering invasion. Epigenetic regulation of various genes was essential for lung cancer initiation and development. This study provides insights into the molecular mechanism of neoplastic progression and identifies potential diagnostic biomarkers and therapeutic targets for lung cancer.

Abstract Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age‐related osteoarthritis (OA). In the present study, highly lubricated and drug‐loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)‐modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti‐chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA‐seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO‐/P53 pathway. Notably, the intra‐articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age‐related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

Abstract Efficient neutrophil migration to infection sites plays a vital role in the body's defense against bacterial infections and natural immune responses. Neutrophils have a short lifespan and cannot be mass‐cultured in vitro. Therefore, developing more stable artificial neutrophils (AN) in a controllable manner has become a research focus. However, existing AN lack chemotaxis, which is the ability to migrate toward high‐signal‐concentration positions in a dynamic blood‐ flow environment. Supplying AN with chemotaxis is key to designing AN that are more similar to natural neutrophils in terms of morphology and function. In this study, micrometer‐sized, spherical, biocompatible AN are developed. These AN consist of zeolitic imidazolate framework‐8 nanoparticles encapsulating two enzymes, coacervate droplet frameworks, and outer phospholipid bilayers carrying enzymes. The AN exhibit responsiveness to elevated hydrogen peroxide levels at inflammation sites, actively chemotaxing toward these sites along concentration gradients. They also demonstrate effective combat against Staphylococcus aureus infections. The capabilities of the AN are further validated through in vitro experiments and in vivo evaluations using vascular graft infection models. This study replicates natural neutrophils in terms of chemical composition, functionality, and physiological impact. It introduces new ideas for advancing the development of advanced artificial cells.

Abstract Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia–reperfusion (I/R) injury, we found that the prophylactic administration of a well‐known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R‐induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro‐inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen‐glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R‐induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.

Abstract Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi‐omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population‐specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon‐stimulated genes (ISGs). Validation through multi‐immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune‐negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi‐omics analysis integrating bulk transcriptomic, single‐cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.

Abstract Beijing is undergoing multiple challenges including urbanization, warming and aging. The Beijing megalopolis of 20 million people now suffers more cold‐related than heat‐related deaths. Stratospheric aerosol injection (SAI) geoengineering is designed to lower surface temperatures, so if SAI were ever done, it may reduce future heat‐related mortality, while also increasing cold‐related mortality. Here we use four Earth System Models (ESM) downscaled to 10 km resolution with the Weather Research and Forecasting (WRF) system to capture urban temperature, humidity and wind speeds. Temperature‐related mortality risk were calculated using a distributed lag nonlinear model (DLNM) of the elderly (over 65s) under the dynamically downscaled moderate (RCP4.5) and extreme (RCP8.5) greenhouse gas, and the G4 SAI scenarios. We used population demographics for all five shared socioeconomic pathways (SSP) and various adaptation measures. Heat‐related excess deaths under G4 are 630∼3,160 per year fewer than RCP4.5, while cold‐related deaths are 370∼1,990 more than RCP4.5 during 2060–2069, with a marginally significant net reduction. G4 significantly reduces the excess deaths relative to RCP8.5. Both heat‐related and cold‐related mortality will increase by 240∼490% when the aging population is accounted for, and decrease by 11%, 23% and 44% under low, medium and high adaptation relative to a no adaptation scenario. Dynamical downscaling produces better quality climate simulations than commonly used statistical approaches, and in the case of Beijing, significantly fewer heat‐related deaths. The marginal health benefits of modest future SAI in Beijing may be representative of the population impacts in the extra‐tropics where deaths due to cold are more than those caused by heat.

Artificial intelligence for graph‐structured data has achieved remarkable success in applications such as recommendation systems, social networks, drug discovery, and circuit annotation. Graph convolutional networks (GCNs) are an effective way to learn representations of various graphs. The increasing size and complexity of graphs call for in‐memory computing (IMC) accelerators for GCN to alleviate massive data transmission between off‐chip memory and processing units. However, GCN implementation with IMC is challenging because of the large memory consumption, irregular memory access, and device nonidealities. Herein, a fully binarized GCN (BGCN) accelerator based on computational resistive random‐access memory (RRAM) through software–hardware codesign is presented. The essential operations including aggregation and combination in GCN are implemented on the RRAM crossbar arrays with cooperation between multiply‐and‐accumulation and content‐addressable memory operations. By leveraging the model quantization and IMC on the RRAM, the BGCN accelerator demonstrates less RRAM usage, high robustness to the device variations, high energy efficiency, and comparable classification accuracy compared to the current state‐of‐the‐art GCN accelerators on both graph classification task using the MUTAG and PTC datasets and node classification task using the Cora and CiteSeer datasets. These results provide a promising approach for edge intelligent systems to efficiently process graph‐structured data.

Abstract The design of high‐entropy single‐atom catalysts (HESAC) with 5.2 times higher entropy compared to single‐atom catalysts (SAC) is proposed, by using four different metals (FeCoNiRu‐HESAC) for oxygen reduction reaction (ORR). Fe active sites with intermetallic distances of 6.1 Å exhibit a low ORR overpotential of 0.44 V, which originates from weakening the adsorption of OH intermediates. Based on density functional theory (DFT) findings, the FeCoNiRu‐HESAC with a nitrogen‐doped sample were synthesized. The atomic structures are confirmed with X‐ray photoelectron spectroscopy (XPS), X‐ray absorption (XAS), and scanning transmission electron microscopy (STEM). The predicted high catalytic activity is experimentally verified, finding that FeCoNiRu‐HESAC has overpotentials of 0.41 and 0.37 V with Tafel slopes of 101 and 210 mVdec−1 at the current density of 1 mA cm−2 and the kinetic current densities of 8.2 and 5.3 mA cm−2, respectively, in acidic and alkaline electrolytes. These results are comparable with Pt/C. The FeCoNiRu‐HESAC is used for Zinc–air battery applications with an open circuit potential of 1.39 V and power density of 0.16 W cm−2. Therefore, a strategy guided by DFT is provided for the rational design of HESAC which can be replaced with high‐cost Pt catalysts toward ORR and beyond.

Abstract To investigate the hypolipidemic and modulation effects of probiotics, the golden hamster of hyperlipidemia model was established and intervened with Lactobacillus fermentum GLF‐217 (GLF‐217) and lovastatin (LOV) for 6 weeks. Body weight and serum biochemical indexes were measured, and liver, colonic contents, and feces were collected after autopsy for pathological and gut microbiota analysis. The results showed that the intervention of GLF‐217 and LOV could significantly reduce serum lipid levels and liver fat accumulation in golden hamsters on a high‐fat diet, more importantly, the LOV intervention could cause damage to the liver. The LOV intervention significantly reduced the contents of short‐chain fatty acids (SCFAs) in the colonic and downregulated the abundance of SCFAs‐producing bacteria, but GLF‐217 intake increased butyric acid, thus reducing blood lipids and protected the liver. This study elucidates the possible mechanism of the hypolipidemic effect of probiotics in terms of regulating gut microbiota.

Abstract Diabetic cardiomyopathy (DCM) is a significant cause of heart failure in patients with diabetes, and its pathogenesis is closely related to myocardial mitochondrial injury and functional disability. Studies have shown that the development of diabetic cardiomyopathy is related to disorders in mitochondrial metabolic substrates, changes in mitochondrial dynamics, an imbalance in mitochondrial Ca2+ regulation, defects in the regulation of microRNAs, and mitochondrial oxidative stress. Physical activity may play a role in resistance to the development of diabetic cardiomyopathy by improving myocardial mitochondrial biogenesis, the level of autophagy and dynamic changes in fusion and division; enhancing the ability to cope with oxidative stress; and optimising the metabolic substrates of the myocardium. This paper puts forward a new idea for further understanding the specific mitochondrial mechanism of the occurrence and development of diabetic cardiomyopathy and clarifying the role of exercise‐mediated myocardial mitochondrial changes in the prevention and treatment of diabetic cardiomyopathy. This is expected to provide a new theoretical basis for exercise to reduce diabetic cardiomyopathy symptoms.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

Abstract Background To investigate the distribution pattern of V1+2d in the left superior pulmonary vein and its clinical significance. Methods A retrospective analysis was conducted using three‐dimensional computed tomographic bronchography and angiography (3D‐CTBA) data from 500 lung cancer patients. Statistical analyses were performed to evaluate the incidence and drainage patterns of the three sub‐branches of V1+2d, namely V1+2d1, V1+2d2 and V1+2d3. Furthermore, clinical data from 10 patients' lesions involving V1+2d were reviewed to illustrate the impact of adjacency to V1+2d on the surgical approach. Results The incidences of V1+2d1, V1+2d2 and V1+2d3 were 100%, 76.4% and 100% respectively. The relative interlobar distribution sizes of B3a and B1+2c and the left upper division (LUD) vein type influenced the incidence of V1+2d2 (p B3a patterns. V1+2d2 was entirely absent in the B3a > B1+2c pattern. V1+2d2 exhibited a higher incidence in both the central vein (CV) type and the noncentral vein (NCV) type when compared to the semi‐central vein (SCV) type (100% vs. 100% vs. 64.8%). The most prevalent venous drainage pattern was the three sub‐branches of V1+2d constituting a major trunk to drain (41.2%). All 10 cases with lesions involving V1+2d successfully underwent sublobar resection with no complications, and the surgical margin was ≥2 cm. Conclusions The three sub‐branches of V1+2d exhibit a high incidence with diverse distribution patterns, yet a discernible pattern exists. For inter‐ or multi‐intersegmental nodules involving V1+2d, combined segmentectomy and subsegmentectomy or combined subsegmentectomy can ensure the safe margin.

Abstract There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p

Abstract Background To develop and validate a preoperative nomogram model combining the radiomics signature and clinical features for preoperative prediction of visceral pleural invasion (VPI) in lung nodules presenting as part‐solid density. Methods We retrospectively reviewed 156 patients with pathologically confirmed invasive lung adenocarcinomas after surgery from January 2016 to August 2019. The patients were split into training and validation sets by a ratio of 7:3. The radiomic features were extracted with the aid of FeAture Explorer Pro (FAE). A CT‐based radiomics model was constructed to predict the presence of VPI and internally validated. Multivariable regression analysis was conducted to construct a nomogram model, and the performance of the models were evaluated with the area under the receiver operating characteristic curve (AUC) and compared with each other. Results The enrolled patients were split into training (n = 109) and validation sets (n = 47). A total of 806 features were extracted and the selected 10 optimal features were used in the construction of the radiomics model among the 707 stable features. The AUC of the nomogram model was 0.888 (95% CI: 0.762–0.961), which was superior to the clinical model (0.787, 95% CI: 0.643–0.893; p = 0.049) and comparable to the radiomics model (0.879, 95% CI: 0.751–0.965; p > 0.05). The nomogram model achieved a sensitivity of 90.5% and a specificity of 76.9% in the validation dataset. Conclusions The nomogram model could be considered as a noninvasive method to predict VPI with either highly sensitive or highly specific diagnoses depending on clinical needs.

Abstract The type parameter helps in scattering mechanism analysis and scattering centre identification. However, current approximate solution methods based on spectral estimation are noise‐sensitive and exhibit low accuracy. In this letter, a high‐precision approach for the type parameter based on the alternating direction method of multipliers (ADMM) is proposed. Logarithmic transformation is used to separate the type parameter and the amplitude from the coupling term, and initially obtain the closed‐form solution of the type parameter. Then, the regularization term of l2‐norm is used for denoising. Finally, a joint optimization model based on ADMM is constructed to effectively estimate the type parameter. Simulation results confirm the high accuracy of the proposed approach.

Abstract The gut microbiome has emerged as a potential target for the treatment of cardiovascular disease. Ischemia/reperfusion (I/R) after myocardial infarction is a serious complication and whether certain gut bacteria can serve as a treatment option remains unclear. Lactobacillus reuteri (L. reuteri) is a well‐studied probiotic that can colonize mammals including humans with known cholesterol‐lowering properties and anti‐inflammatory effects. Here, the prophylactic cardioprotective effects of L. reuteri or its metabolite γ‐aminobutyric acid (GABA) against acute ischemic cardiac injury caused by I/R surgery are demonstrated. The prophylactic gavage of L. reuteri or GABA confers cardioprotection mainly by suppressing cardiac inflammation upon I/R. Mechanistically, GABA gavage results in a decreased number of proinflammatory macrophages in I/R hearts and GABA gavage no longer confers any cardioprotection in I/R hearts upon the clearance of macrophages. In vitro studies with LPS‐stimulated bone marrow‐derived macrophages (BMDM) further reveal that GABA inhibits the polarization of macrophages toward the proinflammatory M1 phenotype by inhibiting lysosomal leakage and NLRP3 inflammasome activation. Together, this study demonstrates that the prophylactic oral administration of L. reuteri or its metabolite GABA attenuates macrophage‐mediated cardiac inflammation and therefore alleviates cardiac dysfunction after I/R, thus providing a new prophylactic strategy to mitigate acute ischemic cardiac injury.

Abstract Urban aquatic ecosystems in plains are often subject to extensive anthropogenic pollutant inputs and have prolonged times for pollutant degradation, potentially leading to diverse carbon emission patterns. This study explored carbon emission patterns and underlying mechanisms in Ge Lake and its tributaries, located in an urban area within a plain in China. The results revealed that carbon emissions from rivers were significantly higher than those from the downstream lake. Spatial interpolation analysis further revealed that CO2‐eq emissions from a 1‐km2 river area can be equivalent to those from an area as large as 86‐km2 of the downstream lake. Rivers are the gateway for the entry of organic compounds, often carrying substances that are readily biodegradable. As the river water moves slowly, these compounds accumulate and undergo degradation in rivers before they reach downstream lakes. The findings may benefit the estimates of carbon emissions in these regions with greater precision.

Abstract Due to the excellent characteristics of Synthetic Aperture Radar (SAR), it has become an important technical means for land and sea target detection applications worldwide. However, the SAR image imaging process is often accompanied by speckle noise, which affects the accuracy of target detection. For this problem, this paper proposes an SAR image reconstruction model based on image denoising and feature extraction. Given a noisy SAR image, at each pixel of the image, the value of the singularity index of a metric defined by the signal gradient norm density is calculated. Then through a hierarchical decomposition of these singular indices, a set of pixels containing the most informative feature set of the image is extracted, and a denoised image is reconstructed using the extracted features. In comparison to traditional filtering and denoising techniques such as non‐local filtering, this algorithm achieves remarkable local filtering and denoising effects while preserving the image's texture information. The denoising performance of the proposed method is evaluated through a series of quantitative indicators and visual comparisons. The results demonstrate that this method effectively reduces background clutter, resulting in a higher contrast between the target and the background.

Abstract Background The value of SyMRI‐derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R‐ISS) in participants with multiple myeloma (MM) is unknown. Methods We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Abstract Acute radiation‐induced esophagitis is a common complication of radiotherapy for esophageal, lung, and other malignancies. Therefore, understanding the diagnosis, grading, risk factors, prevention, and treatment of radiation‐induced esophagitis is essential. Currently, there are few consensuses and guidelines on radiation‐induced esophagitis worldwide, mainly the American College of Gastroenterology (ACG) clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE) and the Digestive Endoscopy Society of Chinese Medical Association's “Guidelines for the Diagnosis and Treatment of Reflux Esophagitis.” However, no consensus or guidelines specifically addressing radiation‐induced esophagitis have been established. Efforts have been made to organize experts to draft Chinese consensus or guidelines, but the recommendations in these guidelines also vary owing to differences in expert backgrounds. The clinical practice guidelines presented herein were developed for the first time with the joint participation of Chinese radiotherapy experts. Drugs and methods with clinical significance were selected by reviewing and summarizing the prevention and treatment of radiation‐induced esophagitis and combining them with China's national conditions. After multiple rounds of discussion and revision, clinical practice guidelines were established in line with the needs of Chinese clinicians, providing useful clinical guidance for the prevention and treatment of radiation‐induced esophagitis.

Abstract Recent studies reveal the crucial role of local features in learning robust and discriminative representations for person re‐identification (Re‐ID). Existing approaches typically rely on external tasks, for example, semantic segmentation, or pose estimation, to locate identifiable parts of given images. However, they heuristically utilise the predictions from off‐the‐shelf models, which may be sub‐optimal in terms of both local partition and computational efficiency. They also ignore the mutual information with other inputs, which weakens the representation capabilities of local features. In this study, the authors put forward a novel Attribute‐guided Transformer (AiT), which explicitly exploits pedestrian attributes as semantic priors for discriminative representation learning. Specifically, the authors first introduce an attribute learning process, which generates a set of attention maps highlighting the informative parts of pedestrian images. Then, the authors design a Feature Diffusion Module (FDM) to iteratively inject attribute information into global feature maps, aiming at suppressing unnecessary noise and inferring attribute‐aware representations. Last, the authors propose a Feature Aggregation Module (FAM) to exploit mutual information for aggregating attribute characteristics from different images, enhancing the representation capabilities of feature embedding. Extensive experiments demonstrate the superiority of our AiT in learning robust and discriminative representations. As a result, the authors achieve competitive performance with state‐of‐the‐art methods on several challenging benchmarks without any bells and whistles.

Abstract Background Gastrointestinal cancer poses a serious health threat owing to its high morbidity and mortality. Although immune checkpoint blockade (ICB) therapies have achieved meaningful success in most solid tumors, the improvement in survival in gastrointestinal cancers is modest, owing to sparse immune response and widespread resistance. Metabolic reprogramming, autophagy, and ferroptosis are key regulators of tumor progression. Methods A literature review was conducted to investigate the role of the metabolic reprogramming, autophagy, and ferroptosis in immunotherapy resistance of gastrointestinal cancer. Results Metabolic reprogramming, autophagy, and ferroptosis play pivotal roles in regulating the survival, differentiation, and function of immune cells within the tumor microenvironment. These processes redefine the nutrient allocation blueprint between cancer cells and immune cells, facilitating tumor immune evasion, which critically impacts the therapeutic efficacy of immunotherapy for gastrointestinal cancers. Additionally, there exists profound crosstalk among metabolic reprogramming, autophagy, and ferroptosis. These interactions are paramount in anti‐tumor immunity, further promoting the formation of an immunosuppressive microenvironment and resistance to immunotherapy. Conclusions Consequently, it is imperative to conduct comprehensive research on the roles of metabolic reprogramming, autophagy, and ferroptosis in the resistance of gastrointestinal tumor immunotherapy. This understanding will illuminate the clinical potential of targeting these pathways and their regulatory mechanisms to overcome immunotherapy resistance in gastrointestinal cancers.

Abstract Background The aim of this study was to analyze the effectiveness and safety of H101 in Chinese patients with malignant pleural effusion and ascites (MPE/MA) in the real world. Methods This multicenter, observational, real‐world study recruited patients with MPE/MA caused by malignant tumor receiving H101‐containing treatment between January 2020 and June 2022. Effectiveness was evaluated by overall remission rate (ORR), and safety was evaluated based on adverse events (AEs). Subgroup analysis was performed on patients grouped according to tumor type, the volume of MPE and MA, and dosage of H101. Results A total of 643 eligible patients were enrolled, and 467 received H101 monotherapy and 176 received H101 combined with chemotherapy. The ORR of total patients was60.3% with 388 case of PR. In the H101 monotherapy group, the decrease of MPE or MA was achieved in 282 (60.4%, PR) patients, 176 (37.7%, NC) patients showed no change in volume of MPE or MA, and nine (1.9%, PD) patients showed an increase, yielding an ORR of 60.4% (282/467). The ORR for the combination therapy group was 60.2% (106/176), with 106 cases of PR, 69 cases of NC and one case of PD. Subgroup analyses based on tumor type, volume of MPE and MA, and dosage of H101 all showed high ORR, approximately 60%. The main AEs associated with H101‐containing regimens were fever, nausea and vomiting. No serious AEs occurred in both groups. Conclusion Encouraging clinical benefits and manageable toxicity of H101 against MPE/MA were preliminarily observed in the real‐world clinical setting, indicating that the H101‐containing regimen is reliable, safe, and feasible, providing a novel and effective option for the treatment of this disease.

Abstract Background In this study, the focus was primarily on examining the occurrence of lymph node metastasis in T1 lung adenocarcinoma, while also analyzing the relationship between clinical variables such as imaging characteristics, pathological classifications, and lymph node metastasis. Methods We retrospectively analyzed data from patients with T1 lung adenocarcinoma who underwent lobectomy and lymph node dissection between January 2016 and December 2019. Utilizing univariate and multivariate analyses, we assessed the associations between lymph node metastasis and various clinical factors, including imaging characteristics, lesion location and depth, and pathological subtypes. Results Of the 433 patients with T1 lung adenocarcinoma, 139 had lymph node metastasis. Moreover, the incidence of node 1 (N1) lymph node, sequential, and node 2 (N2) skip metastases were 12.2%, 12.7%, and 7.2%, respectively. Univariate analysis revealed that tumor diameter, depth ratio, sex, invasive imaging features, and pathological subtype were significantly associated with lymph node metastasis. Multivariate analysis revealed that the tumor depth ratio, tumor diameter, pleural indentation or traction sign, nonvascular penetration sign, solid component, nonadherence, and micropapillary pathological subtype were risk factors for lymph node metastasis. In the multivariate analysis, the micropapillary pathological subtype was an independent risk factor for N2 skip metastasis. Conclusions In patients with clinical stage T1 lung adenocarcinoma, the risk of lymph node metastasis is higher for tumors located deep within the lung tissue with solid components, invasive preoperative imaging features, and larger diameters. For N2 skip lymph node metastasis, the micropapillary pathological subtype represents a significant high‐risk factor.

Abstract Neutropenia is the most common hematological toxicity of concurrent chemoradiotherapy (CCRT), and leads to subsequent treatment delays and/or dose reductions. Neutropenia often advances to febrile neutropenia and serious infections, which can affect the prognosis and safety of patients. The reasonable prevention and management of neutropenia is vital for patients with malignancies undergoing CCRT. Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF), a long‐acting recombinant human granulocyte colony‐stimulating factor, can prevent and treat neutropenia in more convenient clinical settings. Based on relevant guidelines and the most recent clinical data, the Chinese Association for Therapeutic Radiation Oncologists, China Society for Radiation Oncology, and Chinese Association of Radiation Therapy have evaluated the safety and efficacy of PEG‐rhG‐CSF during CCRT, clearly defined the clinical pathway and route of administration for the prevention and treatment of neutropenia, and formed a Chinese expert consensus on PEG‐rhG‐CSF application during CCRT, with the goal of promoting the reasonable clinical use of this treatment.

Abstract Remimazolam is a new benzodiazepine with a short half‐life, good efficacy, and safety profiles in general anesthesia. Combining esketamine with propofol (P + E) could reduce propofol consumption and injection pain. It is, however, unclear if a low dose of remimazolam co‐administrated with esketamine (R + E) is comparable to the increasingly used P + E for surgical abortion with general anesthetic. We conducted a double‐blind randomized controlled trial to compare the efficacy and safety of R + E and P + E. Two hundred patients scheduled for a surgical abortion were randomized to receive remimazolam 0.3 mg/kg plus esketamine 0.3 mg/kg (R + E), and propofol 2 mg/kg plus esketamine 0.3 mg/kg (P + E). Sedative effectiveness was evaluated by measuring the time to lose consciousness (LOC), recovery time, and successful sedation rate. Safety was assessed by hemodynamics and adverse events during and postoperation. The time to LOC and recovery time in R + E was 5 s shorter and 1 min longer than that in P + E, respectively (both p

Abstract Aim To explore the acquisition behaviours for nutrition‐related information of older adults in a long‐term care facility. Design A qualitative descriptive design was used in this study. Methods Sixteen older adults in a long‐term care facility were recruited using purposive sampling between March and May 2021. Data were collected via face‐to‐face semi‐structured interviews, based on open questions regarding acquisition behaviours for nutrition‐related information and flexible question formulation, and the data were analysed using an inductive–deductive method. A health promotion model was used as a conceptual framework to regulate the refinement of themes. Results Three themes were identified in this study. The first theme discussed the individual characteristics and experiences of older adults that contributed to their acquisition behaviours for nutrition‐related information. The second theme described behaviour‐specific cognitions of and the effects on the participants regarding the influencing factors involving various internal individual elements and external physical environment. The third theme explored the positive behavioural outcomes of the participants resulting from these acquisition behaviours. Conclusion Acquisition behaviours for nutrition‐related information of older adults in long‐term care facilities were affected by both individual characteristics and external physical environment factors. Access to nutritional information can help older adults cultivate a healthy diet. Although they exhibited a significant interest in nutrition, the participants still encountered several difficulties. Based on the actual care needs of the older people, appropriate nutritional information interventions should be provided by healthcare providers working in long‐term care facilities so as to improve the ability of the older people to acquire information independently. Patient or public contribution All 16 participants actively participated in the interview process and the preliminary preparation of the article.

Abstract Purpose The role and mechanism of zinc finger DHHC protein 11B (ZDHHC11B) in lung adenocarcinoma (LUAD) remain unclear. We, thus, analyzed the expression pattern, biological function, and potential mechanism of ZDHHC11B in LUAD. Methods The expression level and prognostic value of ZDHHC11B were evaluated based on The Cancer Genome Atlas (TCGA) database and further confirmed in LUAD tissues and cells. The effect of ZDHHC11B on the malignant biological progression of LUAD was evaluated in vitro and in vivo. Gene set enrichment analysis (GSEA) and western blot were used to explore the molecular mechanisms of ZDHHC11B. Results In vitro, ZDHHC11B inhibited the proliferation, migration, and invasion of LUAD cells and induced the apoptosis of LUAD cells. In addition, ZDHHC11B inhibited the growth of tumors in nude mice. GSEA revealed that ZDHHC11B expression is positively correlated with epithelial–mesenchymal transition (EMT). Western blot analysis demonstrated that molecular markers of EMT were inhibited under ZDHHC11B overexpression conditions. Conclusions Our findings indicated that ZDHHC11B plays a significant role in inhibiting tumorigenesis via EMT. In addition, ZDHHC11B may be a candidate molecular target for LUAD treatment.

Abstract Background To assess the prognostic effect of plasma Epstein–Barr virus (EBV) DNA load after induction chemotherapy (postIC‐EBV DNA) on survival outcomes in locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). Methods Patients who were diagnosed with LA‐NPC between August 2017 and October 2021 were included. The chi‐squared test, receiver operating characteristic, Kaplan–Meier survival analysis, and Cox proportional hazard model were used for statistical analysis. Results We included 172 patients with EBV DNA‐positive LA‐NPC in this study. There were 35.5% (n = 61) of patients had plasma residual EBV DNA after induction chemotherapy (IC). Patients with higher EBV DNA before IC (p

Abstract Despite the potential of protein therapeutics, the cytosolic delivery of proteins with high efficiency and bioactivity remains a significant challenge owing to exocytosis and lysosomal degradation after endocytosis. Therefore, it is important to develop a safe and efficient strategy to bypass endocytosis. Inspired by the extraordinary capability of filamentous‐actin (F‐actin) to promote cell membrane fusion, a cyanine dye assembly‐containing nanoplatform mimicking the structure of natural F‐actin is developed. The nanoplatform exhibits fast membrane fusion to cell membrane mimics and thus enters live cells through membrane fusion and bypasses endocytosis. Moreover, it is found to efficiently deliver protein cargos into live cells and quickly release them into the cytosol, leading to high protein cargo transfection efficiency and bioactivity. The nanoplatform also results in the superior inhibition of tumor cells when loaded with anti‐tumor proteins. These results demonstrate that this fusogenic nanoplatform can be valuable for cytosolic protein delivery and tumor treatment.

Site investigation is crucial in geotechnical engineering. The cone penetration test (CPT) and the multichannel analysis of surface waves (MASWs) are widely used as geotechnical and geophysical methods, respectively. CPT offers high precision but requires a high cost and only provides soil information at limited locations. In contrast, MASW covers a broad range of soil information but has less accuracy compared to CPT. This study proposes a novel ensemble prediction method that fuses both CPT and MASW data to overcome the limitations of using either dataset alone. The method employs random forest (RF) and gradient boosting decision tree (GBDT) to achieve the transformation between the shear velocity and cone tip resistance (Vs–qc) and the prediction of qc at unknown locations. Unlike traditional empirical regression models, this method provides more accurate and reliable predictions by leveraging the complementary strengths of CPT and MASW. The proposed RF-GBDT ensemble model is validated using data from the New Zealand Geotechnical Database. The results show that the established RF-GBDT ensemble model outperforms simple empirical regression models and various popular machine learning models in the Vs–qc transformation and in predicting qc at unknown locations. Specifically, integrating MASW data increases the R2 at location CPT3 from 0.477 to 0.758, demonstrating that the proposed method can improve the predictions of soil parameters in areas with sparse data.