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Abstract GWASs have linked the 3p21.1 locus, which is associated with the expression levels of NEK4, to bipolar disorder. Here, we use integrative analyses of GWAS statistics and eQTL annotations to establish that elevated NEK4 expression in the hippocampus is associated with an increased risk of bipolar disorder. To further study this association, we generate transgenic male mice that conditionally overexpress NEK4 in the pyramidal neurons of the adult forebrain, or use AAV to overexpress NEK4 in the dorsal hippocampus. Compared to the control mice, male mice of both strains exhibit a shift from a diurnal anxiety state to a nocturnal normal or anxiolytic-like state. Overexpression of NEK4 also affects the circadian fluctuations in dendritic spine morphology and synaptic structure. Furthermore, we show that treatment with lithium ameliorates the effects of NEK4 overexpression in male mice. We then perform phosphoproteomic analyses to demonstrate that the diurnal and nocturnal phosphoproteomic profiles of male control and NEK4 overexpressing mice are different. These results suggest that male mice with different NEK4 expression levels may recapitulate some of the core features observed in patients with bipolar disorder, indicating that interruption of the homeostatic dynamics of synapses may underlie the emotional swings in bipolar disorder.

Cosmetic periorbital and eyelid surgery is a commonly performed procedure in facial plastic surgery. Understanding the biomechanics of periorbital anatomy and its role in aesthetic surgery is essential for achieving optimal outcomes. This review explores the biomechanical processes involved in periorbital age changes and analyzes the impact of cosmetic surgery approaches on these processes. By maintaining the initial mechanical equilibrium of the brows, eyelids, septal fat, and blepharoplasty folds, periorbital and eyelid cosmetic surgery can effectively rejuvenate the appearance. Disruption of this equilibrium can lead to the migration of anatomic components, resulting in signs of aging. Surgeons, by applying biomechanical concepts, can tailor the forces exerted upon the different structures to manifest the patient’s aesthetic aspirations. The key to success in periorbital and eyelid cosmetic surgery lies in re-establishing a dynamic mechanical equilibrium within the periorbital framework.

In multichannel adaptive radar target detection, diverse nonhomogeneous background factors can cause considerable outlier interference, making it challenging to meet the requirements of independent and identically distributed training data. Current methods for screening training data rely on prior knowledge of the number of outliers, often leading to poor performance in real-world scenarios where this number is usually unknown. This paper addresses these issues by focusing on adaptive training data screening when the number of outliers is unknown. First, the outlier set is estimated using maximum likelihood estimation, assuming known covariance matrices of clutter and noise. In particular, the training data is initially ranked based on the generalized inner product of each range cell data, approximately transforming the maximum likelihood estimation of the outlier set to the estimation of the number of outliers. Second, a fast maximum likelihood estimation algorithm is employed to calculate the unknown covariance matrix, and an adaptive screening approach is designed for scenarios with an unspecified number of outliers. Furthermore, to address the adverse effects of outliers on ranking performance, a normalized generalized inner product form is devised utilizing the normalized sampling covariance matrix. This form is subsequently incorporated into an iterative estimation procedure to improve the adaptive screening accuracy of training data. Simulation results demonstrate that the screening accuracy of the normalized generalized inner product exceeds that of the generalized inner product. Moreover, through even a small number of reiterations, maintaining a consistent enhancement in terms of the Normalized Signal-to-Interference Ratio (NSIR) is still possible. Compared with existing methods, the proposed algorithm considerably improves screening performance, especially when the number of outliers is unknown.

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 Liver metastasis remains the primary cause of mortality in patients with colon cancer. Identifying specific driver gene mutations that contribute to metastasis may offer viable therapeutic targets. To explore clonal evolution and genetic heterogeneity within the metastasis, we conducted single-cell exome sequencing on 150 single cells isolated from the primary tumor, liver metastasis, and lymphatic metastasis from a stage IV colon cancer patient. The genetic landscape of the tumor samples revealed that both lymphatic and liver metastases originated from the same region of the primary tumor. Notably, the liver metastasis was derived directly from the primary tumor, bypassing the lymph nodes. Comparative analysis of the sequencing data for individual cell pairs within different tumors demonstrated that the genetic heterogeneity of both liver and lymphatic metastases was also greater than that of the primary tumor. This finding indicates that liver and lymphatic metastases arose from clusters of circulating tumor cell (CTC) of a polyclonal origin, rather than from a single cell from the primary tumor. Single-cell transcriptome analysis suggested that higher EMT score and CNV scores were associated with more polyclonal metastasis. Additionally, a mutation in the TRPS1 (Transcriptional repressor GATA binding 1) gene, TRPS1 R544Q, was enriched in the single cells from the liver metastasis. The mutation significantly increased CRC invasion and migration both in vitro and in vivo through the TRPS1R544Q/ZEB1 axis. Further TRPS1 mutations were detected in additional colon cancer cases, correlating with advanced-stage disease and inferior prognosis. These results reveal polyclonal seeding and TRPS1 mutation as potential mechanisms driving the development of liver metastases in colon cancer.

Geothermal resources are a promising approach to clean renewable energy; 90% of them are deep reservoirs of hot dry rock that require hydraulic fracturing to create a network of connections among wells to enable efficient heat exchange, known as an Enhanced Geothermal System (EGS). The Pohang EGS project in south Korea led to a devasting Mw5.5 earthquake, triggered by the reservoir’s EGS stimulation, the largest earthquake known to have been induced by EGS development. Detailed investigations have been conducted to understand the cause of the Pohang earthquake; the conclusion has been that overpressurized injected fluids migrated into an unknown fault triggering this large earthquake. Detailed velocity images for the source zone of the 2017 Pohang earthquake, which could be helpful for further understanding its inducing mechanism, are unavailable. However, we have assembled detailed aftershock data recorded by 41 local stations installed within about three months after the Mw5.5 Pohang earthquake, and have then applied the Vp/Vs model’s consistency-constrained double-difference seismic tomography method to determine the high-resolution three-dimensional Vp (compressional wave velocity), Vs (shear wave velocity), and Vp/Vs models of the source region that we report here, as well as earthquake locations within the source region. The velocity images reveal that the deep source area of the 2017 Pohang earthquake is dominated by low Vp, high Vs, and low Vp/Vs anomalies, a pattern that can be caused by overpressurized vapors due to high temperatures at these depths. Based on aftershock locations and velocity features, our studies support the conclusion that the 2017 Pohang earthquake was triggered by injected EGS fluids that migrated into a blind fault.

Abstract Background In 2022, our team launched the pioneering national proficiency testing (PT) scheme for the pathological diagnosis of breast cancer, rapidly establishing its credibility throughout China. Aiming to continuously monitor and improve the proficiency of Chinese pathologists in breast pathology, the second round of the PT scheme was initiated in 2023, which will expand the number of participating institutions, and will conduct a nationwide investigation into the interpretation of HER2 0, 1+, and 2+/FISH- categories in China. Methods The methodology employed in the current round of PT scheme closely mirrors that of the preceding cycle in 2022, which is designed and implemented according to the “Conformity assessment—General requirements for proficiency testing”(GB/T27043—2012/ISO/IEC 17043:2010). More importantly, we utilized a statistics-based method to generate assigned values to enhance their robustness and credibility. Results The final PT results, published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927 ), showed that all participants passed the testing. However, a few institutions demonstrated systemic biases in scoring HER2 0, 1+, and 2+/FISH- with accuracy levels below 59%, considered unsatisfactory. Especially, the concordance rate for HER2 0 cases was only 78.1%, indicating challenges in distinguishing HER2 0 from low HER2 expression. Meanwhile, areas for histologic type and grade interpretation improvement were also noted. Conclusions Our PT scheme demonstrated high proficiency in diagnosing breast cancer in China. But it also identified systemic biases in scoring HER2 0, 1+, and 2+/FISH- at some institutions. More importantly, our study highlighted challenges in the evaluation at the extreme lower end of the HER2 staining spectrum, a crucial area for further research. Meanwhile, it also revealed the need for improvements in interpreting histologic types and grades. These findings strengthened the importance of robust quality assurance mechanisms, like the nationwide PT scheme conducted in this study, to maintain high diagnostic standards and identify areas requiring further training and enhancement.

Objective: The aggregation behavior of silk fibroin under specific conditions can influence its kinetic behavior and viscoelastic properties, thereby affecting biological properties of silk fibroin materials. Therefore, this study systematically investigated the self-assembly aggregation behavior of silk fibroin and explored the conditions for enhancing its mechanical performance and biological properties. Methods: Regenerated silk fibroin was extracted and prepared from domestic silkworm cocoons, and the optimal assembly conditions were determined through turbidity experiments. Rheological experiments were conducted to study the influence of Na+ on the kinetic behavior and viscoelastic properties of silk fibroin solutions. Cell proliferation experiments were carried out to investigate the biological properties of silk fibroin. Results: The extracted regenerated silk fibroin primarily exhibited a random coiled structure. The optimal in vitro self-assembly conditions involved assembly of a 4 mg/mL solution at 70 ℃ for 6 hours. The addition of Ca2+ to the silk fibroin solution inhibited in vitro self-assembly, while the addition of Na+ accelerated the assembly rate and increased the degree of assembly. Furthermore, with increasing Na+ concentration, the gel strength of silk fibroin gradually increased, leading to a more stable gel network. Cell proliferation experiments demonstrated that the solution of regenerated silk fibroin was more conducive to cell growth and proliferation than its self-assembled fibers. Conclusion: The concentration, temperature, assembly time, and ions all have an impact on the in vitro self-assembly aggregation behavior of silk fibroin. This study provides preliminary research on the self-assembly aggregation conditions and biological properties of silk fibroin, offering experimental basis for improving the performance of silk fibroin as a food packaging material.

Calcium–magnesium–alumina–silicate (CMAS) corrosion has attracted special attention in the thermal barrier coating (TBC) field. At high temperatures, when CMAS melts, it adheres to the coating surface and penetrates the interior, severely destroying the TBC. In this study, a promising CMAS-phobic and infiltration-inhibiting material, GdPO4, on which molten CMAS is difficult to wet and penetrate, was proposed. These desirable attributes are explained by analyzing the material characteristics of GdPO4 and its interfacial reaction with CMAS. GdPO4 is demonstrated to have low surface energy, making it difficult for molten CMAS to wet and adhere to the surface. When in contact with molten CMAS, a double-layer structured reaction layer consisting of an acicular upper sublayer and a compact lower sublayer is formed on the GdPO4 surface, which can effectively impede molten CMAS spreading and penetration. First-principles calculation results revealed that the reaction layer has low surface energy and low adhesion to CMAS, which are favorable for molten CMAS phobicity. Additionally, the formation of the reaction layer increases the viscosity of the molten CMAS, which can increase melt wetting and penetration. Hence, GdPO4, which exhibits excellent CMAS-phobicity and infiltration-inhibiting ability, is a promising protective layer material for TBCs against CMAS adhesion and attack.

Abstract In order to study the mechanics, acoustic emission (AE) and electromagnetic emission (EME) response law of bursting liability coal at different loading rates, uniaxial compression tests were carried out on coal mass from Konggu Coal Mine. The corresponding relations among mechanical properties, AE and EME signals in the process of coal failure under loading were analyzed, and the energy evolution law of coal failure with bursting liability under loading rate was discussed. The results show that within a certain range of loading rate, the higher the loading rate, the higher the compressive strength and peak load of bursting liability coal, and the shorter the time for coal to reach the peak load. Under different loading rates, the mechanics, AE and EME signals of coal samples can be well corresponded. When the loading rate is low, the number of blocks destroyed of coal sample is large and the block size is relatively small, and the blocks are mainly scattered around the test platform. When the loading rate is high, the number of damaged blocks is relatively small and the block size is relatively large, and the blocks are far away from the test bench. When loading at a low rate, the internal cracks in coal can be fully developed and connected, and the energy release rate is relatively uniform in the process of loading and failure of coal sample. In the case of high loading rate, the energy release rate of coal sample in the loading process is much smaller than that in the moment of failure. Combining the above test results with the actual situation of the working face, it can be concluded that the total energy stored in the coal of fast mining increases and the threshold of impact decreases compared with that of slow mining. Therefore, under the disturbance of external dynamic load, rapid mining is more likely to induce rock burst.

Abstract Background Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. Methods This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. Results The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn’t affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. Conclusions RFID tag witnessing doesn’t negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist’s confidence.

Abstract Background Severe COVID-19 infection has been associated with the development of pulmonary fibrosis, a condition that significantly affects patient prognosis. Understanding the underlying cellular communication mechanisms contributing to this fibrotic process is crucial. Objective In this study, we aimed to investigate the role of the TNFSF12-TNFRSF12A pathway in mediating communication between alveolar macrophages and fibroblasts, and its implications for the development of pulmonary fibrosis in severe COVID-19 patients. Methods We conducted single-cell RNA sequencing (scRNA-seq) analysis using lung tissue samples from severe COVID-19 patients and healthy controls. The data was processed, analyzed, and cell types were annotated. We focused on the communication between alveolar macrophages and fibroblasts and identified key signaling pathways. In vitro experiments were performed to validate our findings, including the impact of TNFRSF12A silencing on fibrosis reversal. Results Our analysis revealed that in severe COVID-19 patients, alveolar macrophages communicate with fibroblasts primarily through the TNFSF12-TNFRSF12A pathway. This communication pathway promotes fibroblast proliferation and expression of fibrotic factors. Importantly, silencing TNFRSF12A effectively reversed the pro-proliferative and pro-fibrotic effects of alveolar macrophages. Conclusion The TNFSF12-TNFRSF12A pathway plays a central role in alveolar macrophage-fibroblast communication and contributes to pulmonary fibrosis in severe COVID-19 patients. Silencing TNFRSF12A represents a potential therapeutic strategy for mitigating fibrosis in severe COVID-19 lung disease.

Abstract In order to further promote the application of cementitious sand gravel (CSG), the mechanical properties and variation rules of CSG material under triaxial test were studied. Considering the influence of fly ash content, water-binder ratio, sand rate and lateral confining pressure, 81 cylinder specimens were designed and made for conventional triaxial test, and the influence laws of stress–strain curve, failure pattern, elastic modulus, energy dissipation and damage evolution of specimens were analyzed. The results showed that the peak of stress–strain curve increased with the increase of confining pressure, and the peak stress, peak strain and energy dissipation all increased significantly, but the damage variable D decreased with the increase of confining pressure. Under triaxial compression, the specimen was basically sheared failure from the bonding surface, and the aggregate generally did not break. Sand rate had a significant effect on the peak stress of CSG, and decreased with the increase of sand rate. Under the conditions of the same cement content, fly ash content and confining pressure, the optimal water-binder ratio 1.2 existed when the sand rate was 0.2 and 0.3. After analyzing and processing the stress–strain curve of triaxial test, a Cuckoo Search-eXtreme Gradient Boosting (CS-XGBoost) curve prediction model was established, and the model was evaluated by evaluation indexes R2, RMSE and MAE. The average R2 of the XGBoost model based on initial parameters under 18 different output features was 0.8573, and the average R2 of the CS-XGBoost model was 0.9516, an increase of 10.10%. Moreover, the prediction curve was highly consistent with the test curve, indicating that the CS algorithm had significant advantages. The CS-XGBoost model could accurately predict the triaxial stress–strain curve of CSG.

Abstract Background Certain occupations may predispose individuals to urolithiasis, a multi-factorial disease. The study aimed to evaluate the prevalence and related factors of nephrolithiasis in medical staff in Qingdao, China. Methods Physical examination results of 5115 in-service medical staff aged 22–60 years old were retrospectively analyzed. Multivariable logistic regression analysis and stratified analyses by age and gender were applied to explore the related factors of nephrolithiasis in these medical staff. Results The overall nephrolithiasis prevalence in medical staff in Qingdao, China was 4.65%. Doctors were more prone to nephrolithiasis than nurses (5.63% vs. 3.96%, P = 0.013) and the peak prevalence (6.69%) was observed in medical staff working in the emergency department (ED). Male gender (OR = 1.615, 95% CI = 1.123–2.323, P = 0.010), overweight or obesity (OR = 1.674, 95% CI = 1.266–2.214, P

Semantic Communication (SC) has emerged as a novel communication paradigm that provides a receiver with meaningful information extracted from the source to maximize information transmission throughput in wireless networks, beyond the theoretical capacity limit. Despite the extensive research on SC, there is a lack of comprehensive survey on technologies, solutions, applications, and challenges for SC. In this article, the development of SC is first reviewed and its characteristics, architecture, and advantages are summarized. Next, key technologies such as semantic extraction, semantic encoding, and semantic segmentation are discussed and their corresponding solutions in terms of efficiency, robustness, adaptability, and reliability are summarized. Applications of SC to UAV communication, remote image sensing and fusion, intelligent transportation, and healthcare are also presented and their strategies are summarized. Finally, some challenges and future research directions are presented to provide guidance for further research of SC.

Abstract As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients.

Abstract Background Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6‐methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD. Methods This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP‐seq), as well as RNA stability tests to ascertain the half‐life and stability of the target genes. Results The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP‐seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis. Conclusion This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular‐based interventions for LUAD.

Portal vein tumor thrombosis (PVTT), a severe complication of hepatocellular carcinoma (HCC), markedly influences patient prognosis by fostering a hypercoagulable state. However, its molecular underpinnings remain largely unexplored. This study sheds light on the critical role of the KIT ligand (KITLG) in modulating expression of the collagen gene COL4A1 via the STAT3-SMAD2 signaling pathway, thereby influencing platelet activation and PVTT development. Extensive analysis of PVTT tissue samples, alongside in vitro and in vivo experiments including cell-platelet interaction assays and PVTT animal models, revealed the mechanism through which KITLG regulates COL4A1 expression, as well as its downstream effects on platelet behavior and the coagulation cascade. Our findings revealed that marked upregulation of COL4A1 expression, mediated by KITLG through the STAT3-SMAD2 pathway, led to increased platelet activation and PVTT formation. KITLG and COL4A1 expression was markedly higher in PVTT tissues than primary HCC tissues, thus highlighting their critical role in the pathophysiological trajectory leading to thrombosis. The finding that the KITLG-COL4A1 signaling axis is a crucial mediator in PVTT development may offer promising new directions for developing targeted diagnostic and therapeutic strategies. This study underscores the importance of the KITLG-COL4A1 axis in PVTT formation and its potential as a therapeutic target in HCC treatment protocols.

Abstract Fetal adenocarcinoma of the lung (FLAC) is a rare form of lung adenocarcinoma and was divided into high-grade (H-FLAC) and low-grade (L-FLAC) subtypes. Despite the existence of some small case series studies, a comprehensive multi-omics study of FLAC has yet to be undertaken. In this study, we depicted the multi-omics landscapes of this rare lung cancer type by performing multi-regional sampling on 20 FLAC cases. A comparison of multi-omics profiles revealed significant differences between H-FLAC and L-FLAC in a multi-omic landscape. Two subtypes also showed distinct relationships between multi-layer intratumor heterogeneity (ITH). We discovered that a lower genetic ITH was significantly associated with worse recurrence-free survival and overall survival in FLAC patients, whereas higher methylation ITH in H-FLAC patients suggested a short survival. Our findings highlight the complex interplay between genetic and transcriptional heterogeneity in FLAC and suggest that different types of ITH may have distinct implications for patient prognosis.

Abstract Current clustering analysis of spatial transcriptomics data primarily relies on molecular information and fails to fully exploit the morphological features present in histology images, leading to compromised accuracy and interpretability. To overcome these limitations, we have developed a multi-stage statistical method called iIMPACT. It identifies and defines histology-based spatial domains based on AI-reconstructed histology images and spatial context of gene expression measurements, and detects domain-specific differentially expressed genes. Through multiple case studies, we demonstrate iIMPACT outperforms existing methods in accuracy and interpretability and provides insights into the cellular spatial organization and landscape of functional genes within spatial transcriptomics data.

The contamination of aquatic environments by organic dye contaminants in industrial wastewater has attracted widespread global attention. The heterogeneous Fenton-like process presents an attractive method for degrading dye pollutants, especially when such reactions are conducted under neutral pH. In this study, Fe2O3/MnO2 composite was employed as a novel heterogeneous catalyst for activating hydrogen peroxide (H2O2) to oxidize and subsequently degrade methylene blue (MB) under neutral pH. Multiple characterization results have confirmed the presence of MnO2 and Fe2O3 as the primary phases of the synthesized compound catalyst. Degradation experiments have demonstrated that the degradation efficiency of MB approaches 100% under the conditions of H2O2 concentration of 0.30% and Fe2O3/MnO2 amount of 0.888 g/L. Furthermore, the Fe2O3/MnO2 catalyst exhibits consistent and outstanding catalytic activity within a broad pH range from 5 to 9 benefiting from the strong interface interaction in Fe2O3/MnO2. The investigation into the kinetics of the Fenton-like reaction indicates that the catalytic degradation of MB by Fe2O3/MnO2 in conjunction with H2O2 follows pseudo-first-order kinetics. Moreover, supplementary scavenging experiments have demonstrated the crucial role played by hydroxyl radicals (·OH) in the catalytic oxidation mechanism of MB. This study offers a promising catalyst for the treatment of dye-containing wastewater under neutral pH condition.

In this study, E-nose, HS-GC-IMS, and HS-SPME-GC–MS technologies were used to evaluate the flavor characteristics of the pileus and stipe of Boletus edulis from eight origins. 23 key Volatile organic compounds (VOCs) with odor activity values (OAVs) > 1 were identified, and 19 aroma types have been identified in Boletus edulis at the same time. Vegetable and earthy were defined as the dominant aroma types for all pileus and stipe samples. Balsamic and musty were the main and characteristic aroma types for the pileus. The highest concentrations of VOCs in the pileus and stipe were originated from Chuxiong Prefecture and Aba Prefecture, respectively. 19 and 16 key VOCs were detected Chuxiong pileus and Aba stipe, respectively, and Methional was the decisive compound that influenced the vegetable aroma type. The results of this study could be helpful for flavor identification and application of pileus and stipe from Boletus edulis.

Abstract Antiferromagnets are competitive candidates for the next generation of spintronic devices owing to their superiority in small‐scale and low‐power‐consumption devices. The electrical manipulation of the magnetization and exchange bias (EB) driven by spin‐orbit torque (SOT) in ferromagnetic (FM)/antiferromagnetic (AFM) systems has become focused in spintronics. Here, the realization of a large perpendicular EB field in Co/IrMn and the effective manipulation of the magnetic moments of the magnetic Co layer and EB field by SOT in Pt/Co/IrMn system is reported. During the SOT‐driven switching process, an asymmetrically manipulated state is observed. Current pulses with the same amplitude but opposite directions induce different magnetization states. Magneto–optical Kerr measurements reveal that this is due to the coexistence of stable and metastable antiferromagnetic domains in the AFM. Exploiting the asymmetric properties of these FM/AFM structures, five spin logic gates, namely AND, OR, NOR, NAND, and NOT, are realized in a single cell via SOT. This study provides an insight into the special ability of SOT on AFMs and also paves an avenue to construct the logic‐in‐memory and neuromorphic computing cells based on the AFM spintronic system.

Mycoplasma bovis pneumonia is a highly contagious respiratory infection caused by Mycoplasma bovis. It is particularly prevalent in calves, posing a significant threat to animal health and leading to substantial economic losses. Dang-Shen-Yu-Xing decoction is often used to treat this condition in veterinary clinics. It exhibits robust anti-inflammatory effects and can alleviate pulmonary fibrosis. However, its mechanism of action remains unclear. Therefore, this study aimed to preliminarily explore the molecular mechanism of Dang-Shen-Yu-Xing decoction for treating mycoplasma pneumonia in calves through a combination of network pharmacology, molecular docking, molecular dynamics simulation methods, and experimental validation. The active components and related targets of Dang-Shen-Yu-Xing decoction were extracted from several public databases. Additionally, complex interactions between drugs and targets were explored through network topology, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Subsequently, the binding affinity of drug to disease-related targets was verified through molecular docking and molecular dynamics simulation. Finally, the pharmacodynamics were verified via animal experiments. The primary network topology analysis revealed two core targets and 10 key active components of Dang-Shen-Yu-Xing decoction against Mycoplasma bovis pneumonia. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the mechanism of Dang-Shen-Yu-Xing decoction for treating mycoplasma bovis pneumonia involved multiple signaling pathways, with the main pathways including PI3K-Akt and IL17 signaling pathways. Moreover, molecular docking predicted the binding affinity and conformation of the core targets of Dang-Shen-Yu-Xing decoction, IL6, and IL10, with the associated main active ingredients. The results showed a strong binding of the active ingredients to the hub target. Further, molecular docking dynamics simulation revealed three key active components of IL10 induced by Dang-Shen-Yu-Xing decoction against Mycoplasma bovis pneumonia. Finally, animal experiments confirmed Dang-Shen-Yu-Xing decoction pharmacodynamics, suggesting that it holds potential as an alternative therapy for treating mycoplasma bovis pneumonia.

BackgroudScrophularia L., a genus of the Scrophulariaceae, is a group of important medicinal plants used for eliminating heat and detoxifying. East Asia has an abundance of potentially medicinal Scrophularia species, and it serves as a secondary diversity center of the genus. However, the genomic resources available for germplasm identification and pharmaceutical exploration of East Asian Scrophularia are insufficient, hindering its commercial and industrial development. Additionally, the interspecific relationships of most East Asian Scrophularia species remain unclear.MethodsIn this study, we sequenced the leaves of 25 East Asian species of the genus Scrophularia, assembled and annotated the complete chloroplast genomes, and subsequently performed comparative and phylogenetic analyses on these genomes.Results and discussionThe conserved plastome length of these 25 species ranged from 151,582 bp to 153,239 bp, containing a total of 132 coding genes, including 18 duplicated genes and 114 unique genes. Through genome alignment of these 25 species, 38-53 repeated sequences and 7 shared SSRs were identified, along with regions with high nucleotide polymorphism (Pi), which could potentially serve as molecular markers for species identification. The genome structure, gene content, and arrangement showed conservation, while variations were observed in the IR boundary regions and IGS. Phylogenetic inferences based on whole plastomes or on coding sequences (CDS) only yielded congruent results. We categorized the 25 East Asian Scrophularia species into six distinct clades and further explored their interspecies relationships using morphological characteristics, such as flower color, the relative position of stamens and corolla, and plant height. This could lay a genetic basis for future resource development of Scrophularia in East Asia.

A theory model with two kinds of material, which are used to describe the axis stress strain relationship of the pipe segment and girth weld joints, is proposed for the pipeline axial deformation analysis, and a pipeline deformation diagram is composed for the axis deformation combination within the pipeline design limit. According to the pipeline deformation diagram, it is found that the strength of the pipe segment at the design limit σbA plays a key role in the strength matching discussion. The pipeline axis deformation could be classified as three categories based on the yield strength σwY, ultimate tensile strength σwcritof the weld joints and the pipe design strength σbA, which are σwY>σbA, σwcrit≥σbA≥σwY and σbA>σwcrit. For σwY>σbA, the axis plastic deformation will distribute along the pipe segment and this is the ideal states for the pipeline. For σbA>σwcrit, the girth weld may fail as stress rupture with tensile strain as low as 0.003. For σwcrit≥σbA≥σwY, the weld joint may endure the plastic deformation, and the material properties of the weld joint may change, such as the toughness may decrease. Charpy-V impact test have shown that the toughness decreases 35 % for 2 % deformation for the weld joints welded by FCAW-S. In this scenario, the girth weld may break up as brittle fracture due to the toughness decrease. This model could be used to explain the girth weld failures, optimize the strength matching and control the risk, especially for the buried high strength pipeline of the high stress locations.

Dry-type on-board traction transformers have attracted considerable attention because of their lightweight and flameproof characteristics. The temperature distribution of winding areas is a critical indicator for representing operation performance. This study developed a calculation model for the dynamic temperature distribution of winding areas in dry-type on-board traction transformers under time-varying environments. First, a dynamic temperature calculation model was proposed based on the principle of thermoelectric analogy. Next, for addressing the transient outlet temperature of air ducts in the model, the influences of environment parameters and air duct size on heat dissipation were investigated, and a calculation model for the transient outlet temperature was proposed. Finally, the validity of the proposed dynamic temperature calculation method was verified experimentally, and the method was compared with conventional computational fluid dynamics numerical simulation using line data. The results revealed that for various structural parameters and time-varying operation scenarios, the proposed method could accurately obtain the temperature distribution in the winding area and could save more than 99% of the time cost compared with the conventional method.© 2017 Elsevier Inc. All rights reserved.

Supergravity is a noncontact volumetric force; when there is a density difference between the two phases, supergravity can strengthen their separation. The removal of nonmetallic inclusions in steel by supergravity technology not only does not cause molten steel to stir back to the mixing but also promotes the rapid floating of inclusions and shortens their floating time in the molten steel. Small inclusions that are difficult to remove can be removed using a supergravity field. The shape of the inclusions affects their floating behavior in molten steel. To study this effect, this study uses the fluid–structure interaction method to track the computational fluid–solid interface state, constructs three inclusions with different aspect ratios in a two-dimensional longitudinal section, and performs simulation studies of the floating behavior of the inclusions in a supergravity field. The effects of the different initial angles of the inclusions on their floating behavior were also compared. The simulation results show that the floating velocity of the inclusions is related to their shape and floating angle, and the faster the floating velocity, the closer the aspect ratio is to 1, or the floating angle is too vertical. For a given length, inclusions with a larger equivalent diameter float faster. In the supergravity field of G = 1000, the inclusions with a length of 1 μm did not undergo rotation; the inclusions with lengths of 10 and 20 μm rotated from the initial angle (45°, 90°) to the horizontal and then floated steadily. The floating velocity of inclusions is related to the real-time angle of inclusions. The rotational state of the inclusions gradually decreases as the gravity coefficient decreases. When G = 50, the inclusions with a length of 20 μm (initial angle of 90°) fail to rotate completely, which also proves that the inclusions are more likely to rotate when initially inclined instead of vertically. In addition, it was concluded that supergravity does not cause anisotropy in steel properties and that the method of removing inclusions from steel by supergravity does not have a substantial negative effect on steel properties. Finally, this study noted that the prediction of the supergravity treatment time using this model should be based on the floating velocity of the inclusions in the horizontal state, and an approximate time for the floating removal of the inclusions is provided based on this conclusion.

Abstract Triple negative breast cancer (TNBC) accounts for 15–20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC.

Environmental sediments mainly consisting of CaO–MgO–Al2O3–SiO2 (CMAS) corrosion are a serious threat to thermal barrier coatings (TBCs), in which Fe element is usually ignored. Gd2Zr2O7 TBCs are famous for their excellent CMAS resistance. In this study, the characteristics of Fe-containing environmental sediments (CMAS-Fe) and their corrosiveness to Gd2Zr2O7 coatings were investigated. Four types of CMAS-Fe glass with different Fe contents were fabricated. Their melting points were measured to be 1322–1344 ℃, and the high-temperature viscosity showed a decreasing trend with increasing Fe contents. The corrosion behavior of four types of CMAS-Fe to Gd2Zr2O7 coatings at 1350 ℃ was investigated. At the initial corrosion stage (0.1 h), anorthite was precipitated in CMAS-Fe with a high Ca : Si ratio, while Fe-garnet was formed in the melt with the highest Fe content. Prolonging the corrosion time resulted in the formation of a reaction layer, which exhibited an interpenetrating network composed of Gd-oxyapatite, ZrO2, and residual CMAS-Fe. Some spinel was precipitated within the reaction layer. After 1 h or even longer time, the reaction layers tended to be stable and compact, which had comparable hardness and fracture toughness to those of Gd2Zr2O7 coatings. Under the cyclic CMAS-Fe attack, the residual CMAS-Fe in the interpenetrating network provided a pathway for the redeposited CMAS-Fe infiltration, resulting in the continuous growth of the reaction layer. As a result, the Gd2Zr2O7 coatings had a large consumption in the thickness, degrading the coating performance. Therefore, the Gd2Zr2O7 coatings exhibit unsatisfactory corrosion resistance to CMAS-Fe attack.

Abstract Aims Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS). Methods A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis. Results During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160–2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS. Conclusions The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress.

Abstract To reduce the learning time and space occupation, this study presents a novel model‐free algorithm for obtaining the Nash equilibrium solution of continuous‐time nonlinear non‐zero‐sum games. Based on the integral reinforcement learning method, a new integral HJ equation that can quickly and cooperatively determine the Nash equilibrium strategies of all players is proposed. By leveraging the neural network approximation and gradient descent method, simultaneous continuous‐time adaptive tuning laws are provided for both critic and actor neural network weights. These laws facilitate the estimation of the optimal value function and optimal policy without requiring knowledge or identification of the system's dynamics. The closed‐loop system stability and convergence of weights are guaranteed through the Lyapunov analysis. Additionally, the algorithm is enhanced to reduce the number of auxiliary NNs used in the critic. The simulation results for a two‐player non‐zero‐sum game validate the effectiveness of the proposed algorithm.

Abstract The COVID-19 pandemic has dramatically threatened the Gulf Cooperation Council (GCC) countries which have a large proportion of foreign workers. The governments of GCC countries have proactively implemented a comprehensive set of policy measures, and up to our knowledge, a systematic analysis of qualitative and quantitative evidence on the government response is still lacking. We summarized the GCC countries’ government response and quantitatively measured that response using four indexes—the Government Response Index, the Stringency Index, the Vaccine Index, and the Initial Response Index, to analyse their response for future pandemic preparedness. Overall, the government response of all the GCC countries to the COVID-19 pandemic has been comprehensive, stringent, and timely. Notably, the GCC countries have implemented comprehensive vaccine policies. In addition, they have worked actively to protect foreign workers to improve their access to health services and secure their essential living conditions, regardless of their immigrant status. All the GCC countries dynamically adjusted their response to the evolving COVID-19 epidemiological burden and started to relax the stringency of the control policies after the Omicron wave, though the governments had different response magnitudes as measured by the four indexes. These findings have provided several important lessons for future pandemic response and preparedness for countries with similar economic, demographic, and health contexts in (1) prompt actions of containment and closure policies with dynamic adjusting, (2) strengthening health system policies, (3) comprehensive vaccination policies with universal access, (4) equitable and free access to testing, diagnosis, and treatment for all, and (5) strengthening the resilience of health systems.

Abstract CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.

Abstract While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreER T2 ; Hif1a fl/fl ) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreER T2 ; Hif1a fl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.

Combining inhibitors is a key strategy to increase inhibitory efficacy because of synergistic effects. In this study, a green pharmaceutical inhibitor, amoxicillin (AML), was screened and compounded with potassium iodide (KI) to successfully obtain a synergistic and highly efficient green inhibitor. The results revealed that AML/KI have excellent anticorrosion ability for Q235 steel in 1 M HCl medium. At the optimal concentration ratio of 2 mM AML +5 mM KI, the inhibition efficiency was up to 97.7%, which was significantly higher than that of AML alone (57.4%). The hybrid inhibitor remarkably hinders the corrosion process by inhibiting both the cathodic and anodic reactions. Scanning electron microscopy, electron dispersive spectroscopy, contact angle measurement, ultraviolet–visible spectrometry and X-ray photoelectron spectroscopy, as well as Fourier transform infrared spectroscopy, results further confirm the outstanding inhibitory effect and the formation of synergistic adsorption films. Through density functional theory (DFT) calculations, we discovered that the KI salt significantly enhances the adsorption characteristics of AML/KI on the Fe surface, which is consistent with the experimental findings. This research paves the way for a new breed of green hybrid corrosion inhibitors to be created.

Abstract Stroke is a leading cause of death and disability worldwide, and early diagnosis and prompt medical intervention are thus crucial. Frequent monitoring of stroke patients is also essential to assess treatment efficacy and detect complications earlier. While computed tomography (CT) and magnetic resonance imaging (MRI) are commonly used for stroke diagnosis, they cannot be easily used onsite, nor for frequent monitoring purposes. To meet those requirements, an electromagnetic imaging (EMI) device, which is portable, non-invasive, and non-ionizing, has been developed. It uses a headset with an antenna array that irradiates the head with a safe low-frequency EM field and captures scattered fields to map the brain using a complementary set of physics-based and data-driven algorithms, enabling quasi-real-time detection, two-dimensional localization, and classification of strokes. This study reports clinical findings from the first time the device was used on stroke patients. The clinical results on 50 patients indicate achieving an overall accuracy of 98% in classification and 80% in two-dimensional quadrant localization. With its lightweight design and potential for use by a single para-medical staff at the point of care, the device can be used in intensive care units, emergency departments, and by paramedics for onsite diagnosis.

Abstract Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro‐photosensitizer and the limited oxidative phototoxicity of post‐photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro‐photosensitizers (Pro‐I‐PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen‐independent therapeutic mechanisms under single‐pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine‐based dyes modified with different nitroaromatic groups, BPN 1−5, are designed and explored as latent hypoxia‐activatable Pro‐I‐PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2‐methoxy‐4‐nitrophenyl decorated dye (BPN 2) is the optimal Pro‐I‐PSs, which can achieve NTR‐activated background‐free fluorescence/photoacoustic dual‐modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen‐independent photoacoustic cavitation effect and a photodynamic type I process at single‐pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic‐tumor photodynamic therapy.

Sepsis, a systemic inflammatory response caused by infection, can lead to sepsis-associated encephalopathy (SAE), characterized by brain dysfunction without direct central nervous system infection. The pathogenesis of SAE involves blood-brain barrier disruption, neuroinflammation and neuronal death, with neuroinflammation being the core process. Nogo-A, a neurite growth-inhibitory protein in the central nervous system, is not well understood in sepsis. This study explores Nogo-A's mechanisms in sepsis, focusing on SAE. Using in vivo and in vitro methods, healthy SPF C57BL/6J male mice were divided into Sham, Nogo-A-NC-Model, and Nogo-A-KD-Model groups, with sepsis induced by abdominal ligation and puncture. Morris water maze tests assessed learning and memory, and brain tissues underwent hematoxylin-eosin (HE) staining, Nissl staining, and Western blot analysis. In vitro, Nogo-A gene knockdown models were constructed using BV-2 microglia cells to study inflammation and oxidative stress. Results showed Nogo-A expression affected learning and memory in septic mice, with knockdown reducing neuronal damage. Bioinformatics analysis suggested Nogo-A may activate reactive oxygen species (ROS) to inhibit p-SHP2, activating mitochondrial autophagy and promoting neuronal apoptosis. Western blot results confirmed that Nogo-A affects mitochondrial autophagy and neuronal survival by inhibiting SHP2 and activating ROS. Nogo-A's role in neuroinflammation and neuroprotection was emphasized, revealing its impact on endoplasmic reticulum (ER) stress, mitochondrial autophagy, and NLRP3 inflammasome activation. This study provides a theoretical basis for SAE treatment, suggesting further multi-gene and multi-pathway analyses and validation in clinical samples. Developing gene therapy and drug interventions targeting Nogo-A pathways will offer more effective treatment strategies.

ABSTRACT Allergic rhinitis (AR) is a global health challenge that particularly affects the quality of life of children. Human rhinovirus (HRV) infection usually causes common cold in the upper respiratory tract (URT) and can also affect airway allergy development, such as asthma exacerbation, but its relationship with AR is poorly understood. The study aimed to gain insight into the characteristics of HRV that is prevalent in AR children and its role in AR severity. A total of 362 children with symptomatic AR were enrolled from southwestern China during 2022–2023, and nasal lavage samples were collected for HRV molecular characterization and cytokine measurement. HRV was detected in 40% of the AR children, with peak detection in autumn. The positive rate was not correlated with whether the subjects were under allergen-specific immunotherapy (AIT). Among the detected HRVs, 42% were species A, 36% were species B, and 22% were species C, involving 21 A genotypes, 6 B genotypes, and 7 C genotypes. HRV positivity was significantly associated with symptom severity (visual analog scale [VAS] score) and elevated levels of local nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 in AR children who did not receive antiallergic treatment. All three species of HRV strains (A1B, A21, B27, B70, and C17) had been isolated and were able to infect respiratory epithelial tissue in vitro. Complete genome sequencing showed that the antigenic epitopes of the isolated HRVs had certain variations. Our work reveals the etiological characteristics of URT-HRV in AR children and suggests a role of HRV infection in the pathogenesis of childhood AR.IMPORTANCEOur study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively associated with the symptom severity in AR children. Elevated nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 levels suggest a potential pathogenic mechanism by which HRV infection induces nasal type 2 immune/inflammation responses and local IgE production in AR patients. In addition, etiological analysis found that the main prevalent HRV species in AR children are A and B (~80%), which is different from acute respiratory infection and asthma exacerbation, where species A and C are dominant. The data reveal the distinct species prevalence characteristics of HRV infection in AR. Finally, we isolated all three species of HRV strains from nasal cavity of AR children with varying degrees of antigenic epitope mutations and in vitro infectivity, highlighting the importance of strengthening monitoring and intervention for respiratory HRV infection in AR children.

Abstract We explored the challenges and solutions for managing data within the Whole Health System (WHS), which operates as a Learning Health System and a patient‐centered healthcare approach that combines conventional and complementary approaches. Addressing these challenges is critical for enhancing patient care and improving outcomes within WHS. The proposed solutions include prioritizing interoperability for seamless data exchange, incorporating patient‐centered comparative clinical effectiveness research and real‐world data to personalize treatment plans and validate integrative approaches, and leveraging advanced data analytics tools to incorporate patient‐reported outcomes, objective metrics, robust data platforms. Implementing these measures will enable WHS to fulfill its mission as a holistic and patient‐centered healthcare model, promoting greater collaboration among providers, boosting the well‐being of patients and providers, and improving patient outcomes.

In order to investigate the dynamic changes of flavor compounds, Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS) combined with Headspace Solid Phase Microextraction Gas Chromatography Mass Spectrometry (HS-SPME-GC–MS) was used to detect the metabolites in different drying processes. A total of 80 volatile compounds and 1319 non-volatile compounds were identified. The trend in the changes of C-8 compounds and sulfur-containing compounds were generally consistent with the trend of key enzyme activities. 479 differential metabolites were identified and revealed that metabolic profiles of compounds in Boletus edulis were altered with increased organic acids and derivatives and lipids and lipid-like molecules. Fatty acids and amino acids were transformed into volatile compounds under the action of enzymes, which played a significant role in the formation of the distinctive flavor of Boletus edulis. Our study provided a theoretical support for fully comprehending the formation mechanism of flavor from Boletus edulis during drying processes.

The southwestern China is a vital ecological safeguard and is characterized by ecological fragility and climate sensitivity.Based on the MOD13A3 NDVI dataset， this study used a pixel dichotomy model to calculate the average Fractional Vegetation Cover （FVC） from 2000 to 2020 annually， during growing seasons， and in each of the four seasons for the whole southwestern China and its provinces， a spatio-temporal variation analysis was then performed on FVC across different time scales.The study also discussed the primary factors influencing FVC changes over the past 21 years， using ERA5 temperature data， GPCP satellite precipitation data， and DEM data.Finally， the Hurst Index was used to predict future FVC trends.（1） The results indicate that from 2000 to 2020， the overall FVC in the eastern part of the southwestern China showed an increasing trend， particularly in Chongqing and Guizhou， while Tibet showed a general decline.（2） Spatially， the FVC generally showed a "higher in the east and lower in the west" trend， with areas where FVC increased accounting for 43.9% of the total area， and areas of decrease accounting for 53.5%.（3） Precipitation promotes FVC， while temperature has varied effects in different regions.（4） Human activity significantly impacts FVC， with promotion， suppression， and no effect zones accounting for 40.4%， 47.6%， and 12.0% of the grid percentage， respectively.（5） Elevation and FVC over different time scales are significantly correlated but both exhibit a pronounced declining trend.FVC increases significantly with slope， but decreases when the slope is greater than 25°.The effect of aspect on FVC in the southwestern China is less significant than that of slope， elevation， and climatic factors.（6） In the future， the FVC in Tibet and the eastern parts of Sichuan， Yunnan， and Guizhou in the southwestern China will increase， while most areas of western Sichuan and the Hengduan Mountains will exhibit a decreasing trend.The results can provide data support and scientific guidance for the formulation of ecological protection plans in the southwestern China.

Abstract The analysis of the eddy‐current field in the wound core widely used in the field of transformer energy conservation is taken as the theme. Adopting the homogenisation idea to consider the unique geometry of the wound core and features of its equivalent multi‐stage circular cross‐section magnetic boundary, a homogeneous model consisting of a columnar material with continuous homogeneous electromagnetic anisotropy is established by deriving the Maxwell equations of the magnetic quasi‐static field in the columnar coordinate system. Finally, a homogeneous fine element model for the eddy‐current field in the wound core is established and the accuracy of the model has been verified by the test platform. The result shows that the homogeneous model can be effectively used for the analysis of the eddy‐current field in the wound core, and the error of calculating the eddy‐current loss under different excitation conditions is less than 6% under the premise of extremely saving the engineering calculation cost, which will help improve the operational performance of the wound core and contribute to the energy‐saving goal of the high‐voltage equipment.

With the maturity of satellite imaging technology, satellite video has attracted more and more attention because of high spatial resolution and temporal resolution. Thus, object tracking as the main application task of satellite videos also becomes a popular research topic. Compared to natural videos, the difficulties of satellite videos object tracking mainly are caused by feature deficiency of small objectives, surroundings, occlusion (OCC), etc. In this article, based on a dual correlation filter (DCF) tracking framework, a new object tracking method for satellite videos is proposed to deal with the above-mentioned problems. For feature deficiency problem, the proposed super-resolution feature enhancement module could improve the feature discriminative ability of objects utilizing the prior information learned by a super-resolution network. For the OCC problem, a multilayer perceptron motion prediction network is designed to predict the position of objects when OCC occurs, which uses an online training strategy. Besides, KNN background subtraction also is introduced to reduce the interference of surroundings. Finally, these above-mentioned processes are combined together appropriately on the DCF tracking framework for better tracking results. Aiming to verify the performance of the proposed method, abundant experiments have been conducted on satellite video datasets. The experimental results show that the design of the proposed tracking method is effective and it also has a conspicuous advantage compared with some state-of-the-art methods.

Abstract Aim Pathologists are currently supposed to be aware of both domestic and international guidelines for breast cancer diagnosis, but it is unclear how successfully these guidelines have been integrated into routine clinical practice in China. Thus, this national proficiency testing (PT) scheme for breast pathology was set up to conduct a baseline assessment of the diagnostic capability of pathologists in China. Methods This national PT plan is designed and implemented according to the “Conformity assessment—General requirements for proficiency testing” (GB/T27043—2012/ISO/IEC 17043:2010). Five cases of breast cancer with six key items, including histologic type, grade, ER, PR, HER2, and Ki67, were selected for testing among 96 participants. The final PT results were published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927/cn/col22/362 ). Results Our study demonstrated that the median PT score was 89.5 (54–100). Two institutions with scores 86%). However, the histologic grade showed low accuracy (74.0%). The unacceptable results mainly included incorrect evaluation of histologic grade (36.7%), inaccurate evaluation of ER/PR/HER2/Ki67 (28.2%), incorrect identification of C-AD as IBC-NST (15.7%), inappropriate use of 1+/2+/3+ rather than staining percentage for ER/PR (6.1%), misclassification of ER/PR