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Abstract Background Despite extensive research on muscle loss in people living with HIV (PLWH), the prevalence and contributing factors specifically among middle‐aged men remain unclear. This study aimed to determine the prevalence of low muscle mass within this demographic and to identify associated factors. Methods A total of 378 men living with HIV were enrolled in the study. They were classified into low muscle mass group if they displayed a skeletal muscle index (SMI) 0.5, P

Abstract The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single‐cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI‐to‐CKD model of unilateral ischemia‐reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co‐localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro‐repair subsets, whereas infiltrating monocyte‐derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling‐associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin‐like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI‐to‐CKD transition, which could be a potential therapeutic target for preventing CKD development.

Abstract Integrated geophysical technology is a necessary and effective means for geothermal exploration. However, integration of geophysical technology for large‐scale surveys with those for geothermal reservoir localization is still in development. This study used the controlled source audio‐frequency magnetotelluric method technology for large‐scale exploration to obtain underground electrical structure information and micromotion detection technology to obtain underground wave velocity structure information. The combination of two detection technologies was used for local identification of geothermal reservoirs. Further, auxiliary correction and inversion constraint were implemented through the audio magnetotelluric sounding technology for maximum authenticity restoration of the near‐ and transition‐field data. Through these technology improvements, a geothermal geological model was established for the Binhai County of Jiangsu Province in China and potential geothermal well locations were identified. On this basis, a geothermal well was drilled nearly 3000 m deep, with a daily water volume of over 2000 m3/day and a geothermal water temperature of 51°C at the well head. It is found that predictions using the above integrated geophysical exploration technology are in good agreement with the well geological formation data. This integrated geophysical technology can be effectively applied for geothermal exploration with high precision and reliability.

Abstract Background Anaplastic lymphoma kinase (ALK) test in advanced non‐small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real‐world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC. Methods In this real‐world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)‐VENTANA‐D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well. Results The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC‐VENTANA‐D5F3 revealed an intra‐hospital consistency rate of 98.2% (879/895) and an inter‐hospital consistency rate of 99.2% (646/651). IHC‐VENTANA‐D5F3 was used in 53.6%, real‐time polymerase chain reaction (RT‐PCR) in 25.4%, next‐generation sequencing (NGS) in 18.3%, and fluorescence in‐situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC‐VENTANA‐D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT‐PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05). Conclusions This study highlights the real‐world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC‐VENTANA‐D5F3 with high consistency and distinct clinicopathological features in ALK‐positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision‐making in NSCLC.

Abstract The highly ordered film assembled by regularly 1D nanostructures has potential prospects in electronic, photoelectronic and other fields because of its excellent light‐trapping effect and electronic transport property. However, the controlled growth of highly ordered film remains a great challenge. Herein, large‐area and highly ordered Bi2S3 film is synthesized on fluorophlogopite mica substrate by chemical vapor deposition method. The Bi2S3 film features hollowed‐out crosslinked network structure, assembled by 1D nanobelts that regularly distribute in three orientations, which agrees well with the first principles calculations. Based on the as‐grown Bi2S3 film, the broadband photodetector with a response range from 365 to 940 nm is fabricated, exhibiting a maximum responsivity up to 98.51 mA W–1, specific detectivity of 2.03 × 1010 Jones and fast response time of 35.19 ms. The stable instantaneous on/off behavior for 500 cycles and reliable photoresponse characteristics of the Bi2S3 photodetector after storage in air for 6 months confirm its excellent long‐term stability and air stability. Significantly, as sensing pixel and signal receiving terminal, the device successfully achieves high‐resolution imaging of characters of “H”, “I” and “T”, and secure transmission of confidential information. This work shows a great potential of the large‐area and highly ordered Bi2S3 film toward the development of future multiple functional photoelectronic applications.

Background The association between nonalcoholic fatty liver disease and cardiovascular disease is firmly established, yet the association between noninvasive liver fibrosis scores and cardiovascular events remains a topic of uncertainty. Our study aimed to explore the association between liver fibrosis and heart failure. Methods and Results The data set was from the National Health and Nutrition Examination Survey 2011 to 2018. Advanced hepatic fibrosis risk was assessed through 3 noninvasive liver fibrosis scores: Fibrosis‐4 score (FIB‐4), the nonalcoholic fatty liver disease fibrosis score (NFS), and the aspartate aminotransferase to platelet ratio index (APRI). We included 19 695 eligible participants. The national prevalence of advanced liver fibrosis risk in the United States was 4.20%, 8.06%, and 0.35% as determined by FIB‐4, NFS, and APRI scores, respectively. Weighted logistic regression analysis revealed significant associations between advanced liver fibrosis risk and the prevalence of heart failure (continuous variables, FIB‐4: odds ratio [OR], 1.15 [95% CI, 1.07–1.23]; NFS: OR, 1.42 [95% CI, 1.23–1.64]; APRI: OR, 1.44 [95% CI, 1.15–1.81]). When the scores were assessed as categorical variables, the results were still significant (FIB‐4 ≥2.67 versus FIB‐4

ABSTRACT Background Early detection of bladder cancer (BCa) can have a positive impact on patients' prognosis. However, there is currently no widely accepted method for early screening of BCa. We aimed to develop an efficient, clinically applicable, and noninvasive method for the early screening of BCa by detecting specific serum miRNA levels. Methods A mixed‐cohort (including BCa, 12 different other cancers, benign disease patients, and health population) study was conducted using a sample size of 16,189. Five machine learning algorithms were utilized to develop screening models for BCa using the training dataset. The performance of the model was evaluated using receiver operating characteristic curve and decision curve analysis on the testing dataset, and subsequently, the model with the best predictive power was selected. Furthermore, the selected model's screening performance was evaluated using both the validation set and external set. Results The BCaS3miR model, utilizing only three serum miRNAs (miR‐6087, miR‐1343‐3p, and miR‐5100) and based on the KNN algorithm, is the superior screening model chosen for BCa. BCaS3miR consistently performed well in both the testing, validation, and external sets, exceeding 90% sensitivity and specificity levels. The area under the curve was 0.990 (95% CI: 0.984–0.991), 0.964 (95% CI: 0.936–0.984), and 0.917 (95% CI: 0.836–0.953) in the testing, validation, and external set. The subgroup analysis revealed that the BCaS3miR model demonstrated outstanding screening accuracy in various clinical subgroups of BCa. In addition, we developed a BCa screening scoring model (BCaSS) based on the levels of miR‐1343‐3p/miR‐6087 and miR‐5100/miR‐6087. The screening effect of BCaSS is investigated and the findings indicate that it has predictability and distinct advantages. Conclusions Using a mixed cohort with the largest known sample size to date, we have developed effective screening models for BCa, namely BCaS3miR and BCaSS. The models demonstrated remarkable screening accuracy, indicating potential for the early detection of BCa.

Abstract Pulmonary arterial hypertension (PAH) is associated with aberrant pulmonary vascular smooth muscle cell (PASMC) function and vascular remodeling. MiR‐30d plays an important role in the pathogenesis of several cardiovascular disorders. However, the function of miR‐30d in PAH progression remained unknown. Our study shows that circulating miR‐30d level is significantly reduced in the plasma from PAH patients. In miR‐30d transgenic (TG) rats, overexpressing miR‐30d attenuates monocrotaline (MCT)‐induced pulmonary hypertension (PH) and pulmonary vascular remodeling. Increasing miR‐30d also inhibits platelet‐derived growth factor‐bb (PDGF‐bb)‐induced proliferation and migration of human PASMC. Metadherin (MTDH) and phosphodiesterase 5A (PDE5A) are identified as direct target genes of miR‐30d. Meanwhile, nuclear respiratory factor 1 (NRF1) acts as a positive upstream regulator of miR‐30d. Using miR‐30d knockout (KO) rats treated with sildenafil, a PDE5A inhibitor that is used in clinical PAH therapies, it is further found that suppressing miR‐30d partially attenuates the beneficial effect of sildenafil against MCT‐induced PH and vascular remodeling. The present study shows a protective effect of miR‐30d against PAH and pulmonary vascular remodeling through targeting MTDH and PDE5A and reveals that miR‐30d modulates the beneficial effect of sildenafil in treating PAH. MiR‐30d should be a prospective target to treat PAH and pulmonary vascular remodeling.

Abstract Objective Incontinence seriously affects the lives of middle‐aged and older people. Pelvic floor muscle assessment is very important for incontinence, and handgrip strength can be used as an auxiliary diagnostic tool. Our study aims to find new cutoff points of handgrip strength as early indicators of incontinence and analyze the association between low handgrip strength and incontinence among Chinese middle‐aged and older people. Methods Participants were recruited from the 2015 China Health and Retirement Longevity Study. Receiver operating characteristic (ROC) curves were used to find the handgrip strength cutoff point. Logistic regression analysis was performed to explore other incontinence‐related risk factors. Results The study included 10,229 middle‐aged and older people. Compared with normal handgrip strength participants, medium strength participants had 1.510 [men, 95% confidence interval (CI) = 1.017–2.243] and 1.792 (women, 95% CI = 1.294–2.480) times greater risk of incontinence, and low strength participants had 2.420 (men, 95% CI = 1.787–3.277) and 1.516 (women, 95% CI = 1.130–2.032) times greater risk of incontinence. Trend test results showed that the risk of incontinence increased with decreasing handgrip strength in middle‐aged and older people. Conclusions Our study suggests that handgrip strength

Abstract Background Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample‐based methylation changes of skeletal muscle function‐related factors in patients with sarcopenia. Methods The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age‐ and sex‐matched non‐sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation‐specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut‐off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. Results Among 1149 cytosine‐phosphate‐guanine (CpG) sites of 27 skeletal muscle function‐related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation‐specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P

Abstract The AIoT, with its artificial intelligence capabilities, can further enhance Device‐to‐Device (D2D) communication. Based on Non‐Orthogonal Multiple Access (NOMA), D2D technology can effectively alleviate wireless spectrum resource pressure and improve the capacity of heterogeneous cellular networks. However, it also introduces significant system interference issues. In this paper, a resource allocation algorithm is proposed for the NOMA‐D2D heterogeneous cellular network, based on a multi‐agent deep reinforcement learning framework. Firstly, the algorithm allocates appropriate channels to D2D clusters. Then, the power allocation factors and D2D transmit power are jointly optimized to suppress the interference and improve the system performance. Simulation results show that both the channel allocation efficiency and the power control performance of the system can be significantly improved.

Abstract The effects of evodiamine (EVO) on oral squamous cell carcinoma (OSCC) are not yet understood. Based on our earlier findings, we hypothesized that evodiamine may affect OSCC cell proliferation and glutamate metabolism by modulating the expression of EPRS (glutamyl‐prolyl‐tRNA synthetase 1). From GEPIA, we obtained EPRS expression data in patients with OSCC as well as survival prognosis data. An animal model using Cal27 cells in BALB/c nude mice was established. The expression of EPRS was assessed by immunofluorescence, Western blotting, and quantitative PCR. Glutamate measurements were performed to evaluate the impact of evodiamine on glutamate metabolism of Cal27 and SAS tumor cells. transient transfection techniques were used to knock down and modulate EPRS in these cells. EPRS is expressed at higher levels in OSCC than in normal tissues, and it predicts poor prognosis in patients. In a nude mouse xenograft model, evodiamine inhibited tumor growth and the expression of EPRS. Evodiamine impacted cell proliferation, glutamine metabolism, and EPRS expression on Cal27 and SAS cell lines. In EPRS knockdown cell lines, both cell proliferation and glutamine metabolism are suppressed. EPRS's overexpression partially restores evodiamine's inhibitory effects on cell proliferation and glutamine metabolism. This study provides crucial experimental evidence supporting the potential therapeutic application of evodiamine in treating OSCC. Evodiamine exhibits promising anti‐tumor effects by targeting EPRS to regulate glutamate metabolism.

Abstract Intra‐tumour immune infiltration is a crucial determinant affecting immunotherapy response in non‐small cell lung cancer (NSCLC). However, its phenotype and related spatial structure have remained elusive. To overcome these restrictions, we undertook a comprehensive study comprising spatial transcriptomic (ST) data (28 712 spots from six samples). We identified two distinct intra‐tumour infiltration patterns: immune exclusion (characterised by myeloid cells) and immune activation (characterised by plasma cells). The immune exclusion and immune activation signatures showed adverse and favourable roles in NSCLC patients' survival, respectively. Notably, CD14+APOE+ cells were recognised as the main cell type in immune exclusion samples, with increased epithelial‒mesenchymal transition and decreased immune activities. The co‐location of CD14+APOE+ cells and MMP7+ tumour cells was observed in both ST and bulk transcriptomics data, validated by multiplex immunofluorescence performed on 20 NSCLC samples. The co‐location area exhibited the upregulation of proliferation‐related pathways and hypoxia activities. This co‐localisation inhibited T‐cell infiltration and the formation of tertiary lymphoid structures. Both CD14+APOE+ cells and MMP7+ tumour cells were associated with worse survival. In an immunotherapy cohort from the ORIENT‐3 clinical trial, NSCLC patients who responded unfavourably exhibited higher infiltration of CD14+APOE+ cells and MMP7+ tumour cells. Within the co‐location area, the MK, SEMA3 and Macrophage migration inhibitory factor (MIF) signalling pathway was most active in cell‒cell communication. This study identified immune exclusion and activation patterns in NSCLC and the co‐location of CD14+APOE+ cells and MMP7+ tumour cells as contributors to immune resistance.

Abstract Engineered bacteria‐mediated antitumor approaches have been proposed as promising immunotherapies for cancer. However, the off‐target bacterial toxicity narrows the therapeutic window. Living microbes will benefit from their controllable immunogenicity within tumors for safer antitumor applications. In this study, a genetically encoded microbial activation strategy is reported that uses tunable and dynamic expression of surface extracellular polysaccharides to improve bacterial biocompatibility while retaining therapeutic efficacy. Based on screening of genes associated with Salmonella survival in macrophages, a novel attenuated Salmonella chassis strain AIS (htrA gene‐deficient) highly enriched in tumors after administration and rapidly cleared from normal organs are reported. Subsequently, an engineered bacterial strain, AISI‐H, is constructed based on the AIS strain and an optimized quorum‐sensing regulatory system. The AISI‐H strain can achieve recovery of dynamic tumor‐specific bacterial virulence through a novel HTRA‐RCSA axis‐based and quorum‐sensing synthetic gene circuit‐mediated increase in extracellular polysaccharide content. These strains act “off” in normal organs to avoid unwanted immune activation and “on” in tumors for precise tumor suppression in mice. The AISI‐H strain shows significant tumor inhibition and potent activation of anticancer immunity in a melanoma mouse model. The AISI‐H strain exhibits excellent biocompatibility. This bacterial regulation strategy expands the applications of microbe‐based antitumor therapeutics.

Abstract Backgroud Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell‐free DNA (cfDNA) in patients with non‐small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell‐free RNA (cfRNA) is critical for resolving the issue. Methods A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT‐qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi‐gene mutations detection by RT‐qPCR. Results Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4‐ALK, ROS1, RET fusions, and MET ex14 skipping. Conclusion These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA‐based assay.

Abstract The Central Asian Orogenic Belt (CAOB) was formed by the aggregation and collage of numerous Paleozoic subduction‐accretion assemblages and Precambrian microcontinental blocks. However, the tectonic nature of the southeastern CAOB remains controversial, which complicates the reconstruction of the Paleo‐Asian Ocean. To address this issue, a deep seismic reflection survey was initiated across the southeastern CAOB and reveals broad gentle sub‐horizontal reflectors in the middle‐lower crust and a relatively transparent zone in the upper crust. Combining with the Precambrian geological outcrops and other geophysical features, we support a microcontinental block, the Xilinhot Block, existed in the Paleo‐Asian domain. Thus, the Paleo‐Asian Ocean was separated into two branches that underwent north‐dipping and double‐dipping oceanic plate subduction, respectively, to form the Hegenshan‐Heihe and Solonker sutures. Multiple relics beneath Hegenshan‐Heihe Suture indicate that multiple sets of unidirectional oceanic subduction‐accretion and magmatism were important mechanisms of continental growth.

Abstract With 75 known species, the freshwater fish genus Sinocyclocheilus is the largest cavefish radiation in the world and shows multiple adaptations for cave‐dwelling (stygomorphic adaptations), which include a range of traits such as eye degeneration (normal‐eyed, micro‐eyed and eyeless), depigmentation of skin, and in some species, the presence of “horns”. Their behavioural adaptations to subterranean environments, however, are poorly understood. Wall‐following (WF) behaviour, where an organism remains in close contact with the boundary demarcating its habitat when in the dark, is a peculiar behaviour observed in a wide range of animals and is enhanced in cave dwellers. Hence, we hypothesise that wall‐following is also present in Sinocyclocheilus, possibly enhanced in eyeless species compared to eye bearing (normal‐/micro‐eyed species). Using 13 species representative of Sinocyclocheilus radiation and eye morphs, we designed a series of assays, based on pre‐existing methods for Astyanax mexicanus behavioural experiments, to examine wall‐following behaviour under three conditions. Our results indicate that eyeless species exhibit significantly enhanced intensities of WF compared to normal‐eyed species, with micro‐eyed forms demonstrating intermediate intensities in the WF distance. Using a mtDNA based dated phylogeny (chronogram with four clades A–D), we traced the degree of WF of these forms to outline common patterns. We show that the intensity of WF behaviour is higher in the subterranean clades compared to clades dominated by normal‐eyed free‐living species. We also found that eyeless species are highly sensitive to vibrations, whereas normal‐eyed species are the least sensitive. Since WF behaviour is presented to some degree in all Sinocyclocheilus species, and given that these fishes evolved in the late Miocene, we identify this behaviour as being ancestral with WF enhancement related to cave occupation. Results from this diversification‐scale study of cavefish behaviour suggest that enhanced wall‐following behaviour may be a convergent trait across all stygomorphic lineages.

Abstract Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of kidney cancer. Many patients are diagnosed at advanced stages, making early detection crucial. Unfortunately, there are currently no noninvasive tests for ccRCC, emphasizing the need for new biomarkers. Additionally, ccRCC often develops resistance to treatments like radiotherapy and chemotherapy. Identifying biomarkers that predict treatment outcomes is vital for personalized care. The integration of artificial intelligence (AI), multi‐omics analysis, and computational biology holds promise in bolstering detection precision and resilience, opening avenues for future investigations. The amalgamation of radiogenomics and biomaterial‐basedimmunomodulation signifies a revolutionary breakthrough in diagnostic medicine. This review summarizes existing literature and highlights emerging biomarkers that enhance diagnostic, predictive, and prognostic capabilities for ccRCC, setting the stage for future clinical research.

Abstract Sodium‐ion batteries (NIBs) have emerged as a promising alternative to commercial lithium‐ion batteries (LIBs) due to the similar properties of the Li and Na elements as well as the abundance and accessibility of Na resources. Most of the current research has been focused on the half‐cell system (using Na metal as the counter electrode) to evaluate the performance of the cathode/anode/electrolyte. The relationship between the performance achieved in half cells and that obtained in full cells, however, has been neglected in much of this research. Additionally, the trade‐off in the relationship between electrochemical performance and cost needs to be given more consideration. Therefore, systematic and comprehensive insights into the research status and key issues for the full‐cell system need to be gained to advance its commercialization. Consequently, this review evaluates the recent progress based on various cathodes and highlights the most significant challenges for full cells. Several strategies have also been proposed to enhance the electrochemical performance of NIBs, including designing electrode materials, optimizing electrolytes, sodium compensation, and so forth. Finally, perspectives and outlooks are provided to guide future research on sodium‐ion full cells.

Abstract As one of the major causes of antimicrobial resistance, β‐lactamase develops rapidly among bacteria. Detection of β‐lactamase in an efficient and low‐cost point‐of‐care testing (POCT) way is urgently needed. However, due to the volatile environmental factors, the quantitative measurement of current POCT is often inaccurate. Herein, we demonstrate an artificial intelligence (AI)‐assisted mobile health system that consists of a paper‐based β‐lactamase fluorogenic probe analytical device and a smartphone‐based AI cloud. An ultrafast broad‐spectrum fluorogenic probe (B1) that could respond to β‐lactamase within 20 s was first synthesized, and the detection limit was determined to be 0.13 nmol/L. Meanwhile, a three‐dimensional microfluidic paper‐based analytical device was fabricated for integration of B1. Also, a smartphone‐based AI cloud was developed to correct errors automatically and output results intelligently. This smart system could calibrate the temperature and pH in the β‐lactamase level detection in complex samples and mice infected with various bacteria, which shows the problem‐solving ability in interdisciplinary research, and demonstrates potential clinical benefits.

Abstract Background White matter injury (WMI) is an important pathological process after traumatic brain injury (TBI). The correlation between white matter functions and the myeloid cells expressing triggering receptor‐2 (TREM2) has been convincingly demonstrated. Moreover, a recent study revealed that microglial sterol metabolism is crucial for early remyelination after demyelinating diseases. However, the potential roles of TREM2 expression and microglial sterol metabolism in WMI after TBI have not yet been explored. Methods Controlled cortical injury was induced in both wild‐type (WT) and TREM2 depletion (TREM2 KO) mice to simulate clinical TBI. COG1410 was used to upregulate TREM2, while PLX5622 and GSK2033 were used to deplete microglia and inhibit the liver X receptor (LXR), respectively. Immunofluorescence, Luxol fast blue staining, magnetic resonance imaging, transmission electron microscopy, and oil red O staining were employed to assess WMI after TBI. Neurological behaviour tests and electrophysiological recordings were utilized to evaluate cognitive functions following TBI. Microglial cell sorting and transcriptomic sequencing were utilized to identify alterations in microglial sterol metabolism‐related genes, while western blot was conducted to validate the findings. Results TREM2 expressed highest at 3 days post‐TBI and was predominantly localized to microglial cells within the white matter. Depletion of TREM2 worsened aberrant neurological behaviours, and this phenomenon was mediated by the exacerbation of WMI, reduced renewal of oligodendrocytes, and impaired phagocytosis ability of microglia after TBI. Subsequently, the upregulation of TREM2 alleviated WMI, promoted oligodendrocyte regeneration, and ultimately facilitated the recovery of neurological behaviours after TBI. Finally, the expression of DHCR24 increased in TREM2 KO mice after TBI. Interestingly, TREM2 inhibited DHCR24 and upregulated members of the LXR pathway. Moreover, LXR inhibition could partially reverse the effects of TREM2 upregulation on electrophysiological activities. Conclusions We demonstrate that TREM2 has the potential to alleviate WMI following TBI, possibly through the DHCR24/LXR pathway in microglia.

Abstract Introduction Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. Methods A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. Results Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. Conclusion This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

Abstract Tumor‐specific frameshift mutations encoding peptides (FSPs) are highly immunogenic neoantigens for personalized cancer immunotherapy, while their clinical efficacy is limited by immunosuppressive tumor microenvironment (TME) and self‐tolerance. Here, a thermosensitive hydrogel (FSP‐RZ‐BPH) delivering dual adjuvants R848 (TLR7/8 agonist) + Zn2+ (cGAS‐STING agonist) is designed to promote the efficacy of FSPs on murine forestomach cancer (MFC). After peritumoral injection, FSP‐RZ‐BPH behaves as pH‐responsive sustained drug release at sites near the tumor to effectively transform the immunosuppressive TME into an inflammatory type. FSP‐RZ‐BPH orchestrates innate and adaptive immunity to activate dendritic cells in tumor‐draining lymph nodes and increase the number of FSPs‐reactive effector memory T cells (TEM) in tumor by 2.9 folds. More importantly, these TEM also exhibit memory responses to nonvaccinated neoantigens on MFC. This epitope spreading effect contributes to reduce self‐tolerance to maintain long‐lasting anti‐tumor immunity. In MFC suppressive model, FSP‐RZ‐BPH achieves 84.8% tumor inhibition rate and prolongs the survival of tumor‐bearing mice with 57.1% complete response rate. As a preventive tumor vaccine, FSP‐RZ‐BPH can also significantly delay tumor growth. Overall, the work identifies frameshift MFC neoantigens for the first time and demonstrates the thermosensitive bi‐adjuvant hydrogel as an effective strategy to boost bystander anti‐tumor responses of frameshift neoantigens.

Abstract Introduction Dermatomyositis (DM) is often associated with interstitial lung disease (ILD) or pulmonary hypertension (PH). The aim of this study was to investigate the clinical characteristics of DM patients with ILD or PH. Methods This study retrospectively analysed the clinical characteristics of 372 patients with DM, including cytokines, lymphocyte subsets, immunoglobulin and complement. The DM patients were divided into different groups according to whether complicated with ILD, PH or anti‐melanoma differentiation‐associated gene 5 antibodies (MDA5). A qualitative and quantitative data analysis was performed. Results IgG, IgA and IgM in the DM‐associated ILD (ILD‐DM) were higher than that of the DM non‐complicating ILD (Non‐ILD‐DM) (p = 0.022, 0.002 and 0.029, respectively). Meanwhile, IL‐6 (p = 0.008) and IL‐10 (p = 0.001) were increased in the DM‐associated PH (PH‐DM) than in the DM non‐complicating PH (Non‐PH‐DM), while IL‐17 (p = 0.004), double positive (DP) cell ratio and B lymphocyte ratio were reduced in the PH‐DM. Moreover, the incidence of ILD and levels of C4 were higher in the DM with MDA5 (MDA5+ DM) than that of the DM without MDA5. Conclusion ILD‐DM has higher IgG, IgA and IgM than that of Non‐ILD‐DM. PH‐DM has higher IL‐6, IL‐10 and lower IL‐17, DP cell ratio and B lymphocyte ratio than that of Non‐PH‐DM.

Death receptor 5 (DR5) can inhibit malignant proliferation via tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL)‐induced apoptosis in many cancers. Here we examined the expression and sublocalization of DR5 in gastric cancer, as well as its effects on clinical prognosis and cellular processes. Our analysis included a cohort of 240 gastric cancer patients. Bioinformatic analysis showed a significant correlation between DR5 and DNA replication, tumor mutation burden (TMB), and tumor stemness. Unlike death receptor 4 (DR4TRAIL‐R1), DR5 was expressed in the cytoplasm and nucleus, and was found to be positively correlated with lymphovascular invasion, lymph node metastasis, and TNM stage. Patients with positive DR5 had worse overall survival (OS) (P = 0.006). The multivariate Cox model showed that DR5 is an independent poor prognostic factor (hazard ratio = 1.693). Furthermore, knockdown of DR5 inhibited aggressive behaviors, including proliferation and metastasis in gastric cancer cells, and inhibited lung metastasis in vivo. In summary, nuclear localization of DR5 expression is a poor prognosis factor in gastric cancer and promotes growth, invasion, and metastasis of tumor cells in vitro and in vivo.

Abstract Background Immune checkpoint inhibitor (ICI) combination therapies have shown promise in the first‐line treatment of advanced biliary tract cancer (BTC). However, the best partner remains to be validated. Moreover, progress on biomarkers predicting the efficacy of ICI in BTC is slow. This study aimed to assess the efficacy and investigate reliable predictive biomarkers of programmed cell death protein‐1 (PD‐1) antibody combination therapy in the first‐line treatment of advanced BTC. Methods Clinical data from patients with advanced BTC who received chemotherapy or anti‐PD‐1 combination therapy as first‐line were collected. The primary outcome was overall survival (OS). Biomarkers, including peripheral blood inflammation scores, genetic alterations, and tumor microenvironment were investigated. Findings Sixty‐four patients were recruited and divided into four treatment groups: chemotherapy, anti‐PD‐1 plus chemotherapy, anti‐PD‐1 plus targeted therapy, and triple group (anti‐PD‐1 plus chemotherapy and targeted therapy). The median OS was 7.9, 11.3, 12.8, and 28.7 months, respectively. Compared to chemotherapy, mOS significantly prolonged in the triple group (p = 0.031). It showed that patients with five different peripheral blood inflammation scores had significantly prolonged mOS (p 2) group showed significantly superior OS (p = 0.003). Interpretation First‐line anti‐PD‐1 combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune‐inflammation score, FOXP3/CD8 ratio, and PLUS have potential as biomarkers for predicting the efficacy of first‐line anti‐PD‐1 therapy in advanced BTC.

Abstract Background The biomarkers of immune checkpoint inhibitors in the treatment of non‐small cell lung cancer (NSCLC) patients have limited predictive performance. In this study we aimed to investigate the feasibility of molecular tumor burden index (mTBI) in circulating tumor DNA (ctDNA) as a predictor for immunotherapy in patients with NSCLC. Methods From February 2017 to November 2020, pretreatment and on‐treatment (3~6 weeks after first cycle of immunotherapy) dynamic plasma ctDNA samples from NSCLC patients receiving immune monotherapy or combination therapy were analyzed by targeted capture sequencing of 1021 genes. PyClone was used to infer the mTBI. The impact of pretreatment mTBI on survival outcomes was verified in the POPLAR/OAK trials. Results We found that patients without detectable baseline ctDNA had better survival outcomes (median overall survival [OS]: not reached vs. 12.8 months; hazard ratio [HR], 0.15; p = 0.035]). RB1 and SMARCA4 mutations were remarkably associated with worse survival outcomes. Furthermore, lower pretreatment mTBI was associated with superior OS (median: not reached vs. 8.1 months; HR, 0.22; p = 0.024) and PFS (median: 32.9 vs. 5.4 months; HR, 0.35; p = 0.045), but not objective response, which was validated in the POPLAR/OAK cohort, suggesting that baseline mTBI was a prognostic factor for NSCLC immunotherapy. Early dynamic changes of mTBI (ΔmTBI) significantly distinguished responsive patients, and patients with mTBI decrease to more than 68% at the final tumor evaluation had longer OS (median: 38.2 vs. 4.0 months; HR, 0.18; p = 0.017) and PFS (median: not reached vs. 2.3 months; HR, 0.24; p = 0.030). Conclusion ΔmTBI had a good sensitivity to identify potential beneficial patients based on the best effect CT scans, demonstrating that mTBI dynamics were predictive of benefit from immune checkpoint blockade.

Objective Although pilon fractures are rare in clinical practice, they are difficult to treat because of their complexity. Effective fixation of the fracture fragment is the key to the treatment of pilon fractures. Plate osteosynthesis is common clinically, but there are many types of plates and the evaluation of the effect of fixation plates is not comprehensive. This study attempted to compare the capture effect of different fixation plates on the fracture fragments based on 3D modeling and fine distinctions of fracture fragments. Methods The computed tomography (CT) images before treatment of 127 patients with pilon fractures from January 2019 to December 2021 were retrospectively collected. The fracture lines were mapped and digitally displayed as 3D images using MIMICS 21 software. APLUS distal tibia anatomical locking plate (Plate A) and ZIMMER distal tibia anatomical plate (Plate B) were placed on a pseudo‐bone model and CT scans were used to determine the number of screws in the major and minor fragments of pilon fractures. The frequency of the two plates capturing the fracture fragments was recorded. Results Under Assumption 1 or 2, Plate A performed significantly better than Plate B in capturing the major, Chaput, Volkmann, medial malleolus, and die‐punch fracture fragments. Plate A captured markedly more minor fragments than Plate B under Assumption 2 but was not significantly different from Plate B under Assumption 1. Plate A or Plate B showed no obvious difference between major and minor capture rates under the same assumption, and A1 or B1 showed a markedly higher capture rate compared with A2 or B2. In addition, there was a significant positive correlation between the major capture rate and the major fragments in B1, and a significant negative correlation between the minor capture rate and the minor fragments in Plates A and B. However, there was no correlation between the major capture rate of Plate A and the major fragments. Conclusion The APLUS distal tibial anatomical locking plate is superior to the ZIMMER distal tibia anatomical plate in the ability to capture distal tibial fragments in pilon fracture cases.

Abstract Background Neutrophil/lymphocyte ratio (NLR) is a vital index for systemic inflammation and a prognostic indicator for gastric cancer (GC). Despite the abundant literature on NLR's prognostic value for GC, the underlying factors mediating its impact on survival remain unclear. The objective of this study was to analyze the role of NLR in different prognostic models and subgroups, and investigate the mediating effects of immune infiltrates between NLR and survival. Methods A total of 924 patients who underwent D2 lymph node resection were enrolled in this study. According to the level of NLR, patients were divided into two groups, the high and low NLR groups. Clinical parameters, indexes related to immune infiltrates, and survival were compared between the two groups. Prognostic models, interaction analysis, and mediating effects analysis were performed to investigate the clinical association of NLR, immune infiltrates, and survival. Results The infiltration of CD3+ and CD8+ T cells was significantly different in the two NLR groups. The level of NLR was an independent prognostic predictor of GC. In addition, an interaction effect exists between NLR and MMR status on the prognosis of GC (p‐interaction

Abstract Background Bone or brain metastases may develop in 20–40% of individuals with late‐stage non‐small‐cell lung cancer (NSCLC), resulting in a median overall survival of only 4–6 months. However, the primary lung cancer tissue's distinctions between bone, brain and intrapulmonary metastases of NSCLC at the single‐cell level have not been underexplored. Methods We conducted a comprehensive analysis of 14 tissue biopsy samples obtained from treatment‐naïve advanced NSCLC patients with bone (n = 4), brain (n = 6) or intrapulmonary (n = 4) metastasis using single‐cell sequencing originating from the lungs. Following quality control and the removal of doublets, a total of 80 084 cells were successfully captured. Results The most significant inter‐group differences were observed in the fraction and function of fibroblasts. We identified three distinct cancer‐associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory CAF (iCAF) and antigen‐presenting CAF (apCAF). Notably, apCAF was prevalent in NSCLC with bone metastasis, while iCAF dominated in NSCLC with brain metastasis. Intercellular signalling network analysis revealed that apCAF may play a role in bone metastasis by activating signalling pathways associated with cancer stemness, such as SPP1‐CD44 and SPP1‐PTGER4. Conversely, iCAF was found to promote brain metastasis by activating invasion and metastasis‐related molecules, such as MET hepatocyte growth factor. Furthermore, the interaction between CAFs and tumour cells influenced T‐cell exhaustion and signalling pathways within the tumour microenvironment. Conclusions This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell–cell interactions.

Abstract Introduction Approximately 30% of individuals with advanced EC have unsatisfactory prognosis. Evidence suggests that TPX2 is frequently upregulated in malignancies and related to cancer progression. Its role and pathological mechanism in EC need further research. Methods GSEA and TPX2 expression, GO, KEGG, and prognostic analyses were performed with TCGA data by bioinformatic approaches. Relationships between TPX2 expression and clinicopathological parameters were investigated immunohistochemically and statistically. shRNA and overexpression plasmids were constructed and transfected into AN3CA and Ishikawa cells to evaluate phenotypic changes and injected into nude mouse axillae. Coimmunoprecipitation and chromatin immunoprecipitation were used to identify interacting proteins and promoter‐binding sequences. Changes in TPX2 expression were identified by Western blotting and RT–qPCR. Results TPX2 expression was significantly higher in EC tissues than in normal tissues in TCGA and in‐house specimens (all p

Abstract Soft porous organic crystals with stimuli‐responsive single‐crystal‐to‐single‐crystal (SCSC) transformations are important tools for unraveling their structural transformations at the molecular level, which is of crucial importance for the rapid development of stimuli‐responsive systems. Carefully balancing the crystallinity and flexibility of materials is the prerequisite to construct advanced organic crystals with SCSC, which remains challenging. Herein, a squaraine‐based soft porous organic crystal (SPOC‐SQ) with multiple gas‐induced SCSC transformations and temperature‐regulated gate‐opening adsorption of various C1‐C3 hydrocarbons is reported. SPOC‐SQ is featured with both crystallinity and flexibility, which enable pertaining the single crystallinity of the purely organic framework during accommodating gas molecules and directly unveiling gas‐framework interplays by SCXRD technique. Thanks to the excellent softness of SPOC‐SQ crystals, multiple metastable single crystals are obtained after gas removals, which demonstrates a molecular‐scale shape‐memory effect. Benefiting from the single crystallinity, the molecule‐level structural evolutions of the SPOC‐SQ crystal framework during gas departure are uncovered. With the unique temperature‐dependent gate‐opening structural transformations, SPOC‐SQ exhibits distinctly different absorption behaviors towards C3H6 and C3H8, and highly efficient and selective separation of C3H6/C3H8 (v/v, 50/50) is achieved at 273 K. Such advanced soft porous organic crystals are of both theoretical values and practical implications.

Abstract Background The potent immune effects of interleukin‐2 (IL‐2) for cancer therapy can be increased by genetic fusion of IL‐2 to the Fc domain of an antibody (IL‐2‐Fc) or tumor targeted by genetic fusion to a whole antibody known as an immunocytokine (ICK). Methods An anti‐CEA ICK (M5A‐IL‐2) was compared to an IL‐2‐Fc fusion protein using tumor therapy and PET imaging in CEA transgenic immunocompetent mice bearing CEA positive colon or breast tumors. Combination with stereotactic radiation therapy (SRT) was performed with either ICK or IL‐2‐Fc. Results ICK and IL‐2‐Fc had comparable antitumor effects in both tumor models, although ICK had higher tumor uptake and slower blood clearance than an IL‐2‐Fc. Analysis of IFNγ+/CD8+ and FoxP3+/CD4+ T cells revealed higher levels of IFNγ‐producing CD8+ T cells in ICK treated mice versus more efficient Treg elimination in IL‐2‐Fc treated mice. No significant or lasting toxicity was detected for either agent. Combination therapies with SRT revealed comparable efficacy and induction of immune memory for both ICK and IL‐2‐Fc when mice were rechallenged post‐therapy. Conclusions IL‐2‐Fc had comparable antitumor efficacy to CEA‐targeted M5A‐IL‐2 ICK, while both fusion proteins induced immune memory when combined with SRT. Differences in the therapeutic mechanisms of both agents were observed.

Abstract Increasing numbers of studies have shown that tumor cells prefer fermentative glycolysis over oxidative phosphorylation to provide a vast amount of energy for fast proliferation even under oxygen‐sufficient conditions. This metabolic alteration not only favors tumor cell progression and metastasis but also increases lactate accumulation in solid tumors. In addition to serving as a byproduct of glycolytic tumor cells, lactate also plays a central role in the construction of acidic and immunosuppressive tumor microenvironment, resulting in therapeutic tolerance. Recently, targeted drug delivery and inherent therapeutic properties of nanomaterials have attracted great attention, and research on modulating lactate metabolism based on nanomaterials to enhance antitumor therapy has exploded. In this review, the advanced tumor therapy strategies based on nanomaterials that interfere with lactate metabolism are discussed, including inhibiting lactate anabolism, promoting lactate catabolism, and disrupting the “lactate shuttle”. Furthermore, recent advances in combining lactate metabolism modulation with other therapies, including chemotherapy, immunotherapy, photothermal therapy, and reactive oxygen species‐related therapies, etc., which have achieved cooperatively enhanced therapeutic outcomes, are summarized. Finally, foreseeable challenges and prospective developments are also reviewed for the future development of this field.

Abstract Background Growing evidence has revealed the critical regulatory role for circular RNAs (circRNAs) in cancer. This study aimed to explore the function of circ_0001387 in breast cancer (BC). Methods Circ_0001387, miR‐136‐5p, and spindle and kinetochore‐associated protein 2 (SKA2) levels were analyzed by quantitative real‐time polymerase chain reaction. Clone formation and 5‐ethynyl‐2′‐deoxyuridine assays were used to analyze cell proliferation. Cell apoptosis and cell migration and invasion abilities were analyzed using flow cytometry or transwell assay. Mechanism assay was used to confirm the association between miR‐136‐5p and circ_0001387 or SKA2. The effect of circ_0001387 on tumor growth in vivo was analyzed by the xenograft mice model. Results Circ_0001387 and SKA2 were expressed at high levels, whereas miR‐136‐5p was lowly expressed in BC tissues and cells. Meanwhile, the downregulation of circ_0001387 restrained BC cell progression in vitro and in vivo. Circ_0001387 competitively bound to miR‐136‐5p to regulate BC cell malignant behaviors. SKA2 was targeted by miR‐136‐5p, and SKA2 reinstated the suppressive effect of miR‐136‐5p upregulation in BC cells. Conclusion Our study indicated that circ_0001387 contributed to BC cell progression through miR‐136‐5p/SKA2 axis.

Abstract Aim The aim was to examine the effect of role overload, work addiction and leader‐member exchange on missed nursing care. Design A cross‐sectional study. Methods Chinese registered nurses from five Sichuan province public hospitals were studied from March 2022–May 2022. The measurements were derived from a questionnaire on role overload, work addiction, missed nursing care, leader‐member exchange and a sociodemographic datasheet. Descriptive statistics and inferential statistics were conducted (N = 403). Results Role overload was associated with missed nursing care, and work addiction played a mediation role. Leader‐member exchange negatively predicted work addiction and played a moderating role between role overload and work addiction. The effect of role overload on work addiction was attenuated when the level of leader‐member exchange was higher. Promoting leader‐member exchange could mitigate how role overload undermines missed nursing care.

Abstract Background Previous clinical trials indicated the addition of anti‐PD‐1 antibody remarkably improved the efficacy of trastuzumab and chemotherapy in patients with HER2‐positive gastric/gastroesophageal junction (GEJ) cancer. However, no real‐world experiences have been reported yet. Methods We retrospectively analyzed 1212 patients with gastric/GEJ cancer treated at Nanjing Drum Tower Hospital between 2019 and 2022. Among 138 patients with HER2‐positive gastric/GEJ cancer, 47 patients receiving at least two doses of the combination regimen with anti‐PD‐1 antibody, trastuzumab, and chemotherapy were recruited in the study population, and 38 out of 47 patients with measurable disease were included in the efficacy population. Progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity profiles were reported. Results In the study population, 37 (78.7%) received the study therapy as a first‐line treatment. In the efficacy population, the ORR and DCR were 76.3% and 94.7%, respectively. The overall median PFS was 9.1 months (95% confidence interval [CI] 6.3–11.9 months). For the first‐line treatment, the mPFS was 10 months, and 7 months for the second‐line. Among 14 patients who failed the study treatment, three (21.4%) developed brain metastasis as the first failure site. No significant association was found between PFS and the expression of PD‐L1. 22.2% of patients developed grade 3 treatment‐related adverse events (TRAEs). No treatment‐related grade ≥4 adverse events or deaths occurred. Conclusion This real‐world study validated the combination regimen's high efficacy and good tolerance in patients with HER2‐positive gastric/GEJ cancer. An increased incidence of brain metastasis was observed in patients who failed this regimen.

Abstract Background Although endoscopic screening for esophageal cancer has been performed in high‐risk areas in China for decades, there is limited and inconsistent evidence regarding the starting age for individuals participating in screening. The aim of this study is to investigate the optimal starting age of esophageal cancer screening. Methods This study is based on a multicenter prospective cohort consisting 338,017 permanent residents aged 40–69 years in six high‐risk areas of esophageal cancer in China. The participation rate, detection rate, hazard ratios (HRs), cumulative incidence and mortality and number needed to screen (NNS) were calculated in each age group. Screening burden, benefit and risk were compared among screening strategies with different initiation ages to explore the optimal starting age for population‐based screening in high‐risk areas. Results Individuals aged 50–69 had a higher participation rate, a higher detection rate and improved screening effectiveness than those aged 40–49. The endoscopic screening had no significant effect on reducing the incidence of esophageal cancer in individuals under 55 and mortality in individuals under 45. Increasing the starting age to 50 years reduced the screening demand and NNS by 40% and 55%, and resulted in 12% of detectable positive cases, 16% of preventable incident cases, and 14% of preventable deaths being missed. Conclusions Postponing the starting age of endoscopic screening to 50 years might yield a more‐favorable balance between screening benefit and burden in high‐ risk areas with limited resources.

Abstract Doxorubicin (DOX)‐induced cardiotoxicity limits its broad use as a chemotherapy agent. The development of effective and non‐invasive strategies to prevent DOX‐associated adverse cardiac events is urgently needed. We aimed to examine whether and how low‐intensity pulsed ultrasound (LIPUS) plays a protective role in DOX‐induced cardiotoxicity. Male C57BL/6J mice were used to establish models of both acute and chronic DOX‐induced cardiomyopathy. Non‐invasive LIPUS therapy was conducted for four consecutive days after DOX administration. Cardiac contractile function was evaluated by echocardiography. Myocardial apoptosis, oxidative stress, and fibrosis were analyzed using terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL) staining, dihydroethidium (DHE) staining, and picrosirius red staining assays. RNA‐seq analysis was performed to unbiasedly explore the possible downstream regulatory mechanisms. Neutrophil recruitment and infiltration in the heart were analyzed by flow cytometry. The S100a8/a9 inhibitor ABR‐238901 was utilized to identify the effect of S100a8/a9 signaling. We found that LIPUS therapy elicited a great benefit on DOX‐induced heart contractile dysfunction in both acute and chronic DOX models. Chronic DOX administration increased serum creatine kinase and lactate dehydrogenase levels, as well as myocardial apoptosis, all of which were significantly mitigated by LIPUS. In addition, LIPUS treatment prevented chronic DOX‐induced cardiac oxidative stress and fibrosis. RNA‐seq analysis revealed that LIPUS treatment partially reversed alterations of gene expression induced by DOX. Gene ontology (GO) analysis of the downregulated genes between DOX‐LIPUS and DOX‐Sham groups indicated that inhibition of neutrophil chemotaxis might be involved in the protective effects of LIPUS therapy. Flow cytometry analysis illustrated the inhibitory effects of LIPUS on DOX‐induced neutrophil recruitment and infiltration in the heart. Moreover, S100 calcium binding protein A8/A9 (S100a8/a9) was identified as a potential key target of LIPUS therapy. S100a8/a9 inhibition by ABR‐238901 showed a similar heart protective effect against DOX‐induced cardiomyopathy to LIPUS treatment. LIPUS therapy prevents DOX‐induced cardiotoxicity through inhibition of S100a8/a9‐mediated neutrophil recruitment to the heart, suggesting its potential application in cancer patients undergoing chemotherapy with DOX.

Abstract The multiscale micro‐nano pores in coal can result in the ultra‐low permeability of coal, which restricts the efficiency of gas extraction. It is difficult for the conventional seepage‐enhancement measures to affect the nanoscale pores within the coal matrix. Thermal stimulation can reach deep into the micro‐nano pores within coal matrix to improve the permeability. Therefore, it is important to study the diffusivity and permeability of the multiscale micro‐nano pores at different temperatures. In this study, the experiments of diffusion‐seepage measured by the methods of GRI (Gas Research Institution) and steady‐state were conducted using a cylindrical coal at different temperatures and pressures. The experimental results show that the apparent diffusion coefficient of cylindrical coal is not constant but variable dynamically; and the classical diffusion model fails to describe the full‐time process of gas flow accurately. On this basis, a model of multiscale dynamic apparent diffusion‐seepage that can accurately describe the full‐time flow process was proposed. As is observed, the apparent permeability attenuates dynamically with time without stress loading, and the initial apparent permeability and the attenuation coefficient increase monotonically with the rise of temperature. Under the stress constraint, the steady‐state permeability increases after a decrease as the temperature rises, displaying a “U‐shaped” pattern. Without stress constraint, the increasing temperature causes the exterior multiscale pores to expand outward by different degrees so as to increase permeability, while the interior micro‐nano pores show three inward and outward expansion mechanisms. Under stress constraint, at low temperature and high effective stress, the increasing temperature causes pores to expand inward and the permeability decreases accordingly. When temperature continues to increase, coal expands outward because the effective stress is counteracted by the thermal stress, leading to an increase in permeability. This study is of significance for thermal gas extraction engineering.

Abstract Background Observational epidemiological studies suggest that lung cancer risk may be raised by gastroesophageal reflux disease (GERD); however, the causal relationship between them remains unknown. Our study performed the two‐sample Mendelian randomization (MR) approach to examine the causal relationship between GERD and lung cancer. Methods Instrument variables were found to be independent single nucleotide polymorphisms (SNPs) that were highly linked with GERD (n = 129,080). Summary data from genome‐wide association studies (GWAS) data were used to determine outcomes for lung cancer (n = 11,348), squamous cell lung cancer (LUSC), and lung adenocarcinoma (LUAD). In this study, three MR statistical techniques (inverse variance weighted (IVW), MR‐Egger, and weighted median) were used to examine the potential causative relationship between GERD and the risk of lung cancer. Cochran's Q test, MR‐Egger intercept test, leave‐one‐out analysis, and the funnel plot were all used in sensitivity analyses. Results The main IVW method revealed that GERD substantially increased the risk of lung cancer [odds ratio (OR) = 1.37; 95% CI 1.16–1.63, p = 0. 0003], which was also supported by weighted median and MR‐Egger analyses. Using IVW estimate, similar causal relationships were also observed between GERD and LUSC (OR = 1.56; 95% CI 1.26–1.93, p = 5.35 × 10−5) and LUAD (OR = 1.45; 95% CI 1.09–1.93, p = 0.01). Although potential heterogeneity was observed in some studies, random effect IVW was not violated by the heterogeneity, indicating that the causal effect was robust. Conclusion GERD was positively associated with the risk of lung cancer, for LUSC and LUAD. This study shed light on a new direction for prevent strategy of lung cancer and therapeutic perspectives in patients with GERD.

Abstract Objective Aiming to improve the feasibility and reliability of using high‐frequency oscillations (HFOs) for translational studies of epilepsy, we present a pipeline with features specifically designed to reject false positives for HFOs to improve the automatic HFO detector. Methods We presented an integrated, multi‐layered procedure capable of automatically rejecting HFOs from a variety of common false positives, such as motion, background signals, and sharp transients. This method utilizes a time‐frequency contour approach that embeds three different layers including peak constraints, power thresholds, and morphological identification to discard false positives. Four experts were involved in rating detected HFO events that were randomly selected from different posttraumatic epilepsy (PTE) animals for a comprehensive evaluation. Results The algorithm was run on 768‐h recordings of intracranial electrodes in 48 PTE animals. A total of 453 917 HFOs were identified by initial HFO detection, of which 450 917 were implemented for HFO refinement and 203 531 events were retained. Random sampling was used to evaluate the performance of the detector. The HFO detection yielded an overall accuracy of 0.95±0.03, with precision, recall, and F1 scores of 0.92±0.05, 0.99±0.01, and 0.94±0.03, respectively. For the HFO classification, our algorithm obtained an accuracy of 0.97±0.02. For the inter‐rater reliability of algorithm evaluation, the agreement among four experts was 0.94±0.03 for HFO detection and 0.85±0.04 for HFO classification. Significance Our approach shows that a segregated pipeline design with a focus on false‐positive rejection can improve the detection efficiency and provide reliable results. This pipeline does not require customization and uses fixed parameters, making it highly feasible and translatable for basic and clinical applications of epilepsy.

Abstract In digital image processing, feature extraction occupies a very important position, which is related to the effect of image classification or recognition. At present, effective quantum feature extraction methods are relatively lacking. And the current feature extraction methods are mainly devoted to the extraction of basic features of images, failing to consider the global features of classical images and the global features of quantum images comprehensively. In this paper, we propose a dual quantum image feature extraction method named PSQIFE, which focuses on the global energy representation of images by constructing dual quantum image global features. The representation of the global features of the dual quantum image is obtained by quantum superposition of two parts of quantum state features. In this paper, quantum image reconstruction and quantum image fidelity tests are performed on the extracted global features by 9 classes of classical images, and the overall fidelity is above 95%. In addition, the effectiveness of PSQIFE dual quantum image feature extraction method is verified by comparing the image classification test with convolutional feature extraction method on Mnist dataset. The method has some reference significance for the research of quantum image feature extraction and classification.

Abstract Attention‐deficit/hyperactivity disorder (ADHD) often co‐occurs with other psychiatric and physical diseases. However, available evidence on associations between ADHD and cardiovascular diseases (CVDs) is mixed. To systematically review, quantitatively synthesize, and appraise available evidence on the link between ADHD with CVDs, we searched relevant articles in PubMed, Embase, PsycINFO, and Web of Science from inception to May 1, 2022. Study quality was assessed by using the Newcastle‐Ottawa Scale, and random‐effects model meta‐analyses were performed. A total of 18,391,169 (ADHD: n = 421,224) individuals from 11 studies were included in our systematic review and 8,196,648 (ADHD = 332,619) individuals from five studies were included in the main meta‐analysis of adjusted estimates. Pooled estimates showed that ADHD was significantly associated with an increased risk of CVDs in analyses based on adjusted effect size (odds ratio (OR) = 1.96; 95% confidence interval (CI) = 1.19–2.23, Q = 140.74, PQ

Abstract Whereas the presence of flowers on ornamental flowering plants is essential for their identification via traditional methods, ornamental flowering plants cannot be reliably identified in non‐flowering stages likewise. Here, DBALM (DNA Barcodes–Leaf Morphology), a new approach that combines DNA barcoding data with micromorphological features of the leaf epidermis and that is not limited by the flowering stage, was used to identify 16 evergreen rhododendron cultivars. First, the sequences of DNA barcodes, ITS, matK, psbA‐trnH, and rbcL, were obtained from the DNA of leaves. Phylogenetic analysis was conducted to clarify the groupings among all the samples based on the four markers. Then, microscopic features of the leaf epidermis were used to further distinguish individuals from the same clade. DNA barcoding permitted the 16 cultivars to be divided into eight groups. The microscopic features of the leaf epidermis permitted cultivars within the same clade to be distinguished. The matK + psbA‐trnH combination was the most effective barcode combination in this study. In addition, the new primer matK‐Rh_R was designed, and it increased the amplification rate of evergreen rhododendron cultivars to 100%. In sum, DBALM was capable of accurately identifying the 16 evergreen rhododendron cultivars using data collected from a single leaf in the vegetative growth stage. This method can greatly facilitate the identification and breeding of ornamental flowering plants.