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Abstract Peptidoglycan recognition proteins (PGLYRPs) are implicated in the control of the intestinal microbiota; however, molecular requirements for peptidoglycan (PGN) binding and receptor signaling mechanisms remain poorly understood. Here we show that PGLYRP1 is a receptor for the disaccharide motif of lysine N-acetylglucosamine N-acetylmuramic tripeptide (GMTriP-K). PGLYRP1 is required for innate immune activation by GMTriP-K but not muramyl dipeptide (MDP). In macrophages, intracellular PGLYRP1 complexes with NOD2 and GEF-H1, both of which are required for GMTriP-K-regulated gene expression. PGLYRP1 localizes to the endoplasmic reticulum and interacts at the Golgi with NOD2 upon GMTriP-K stimulation. PGLYRP1 and dependent gene expression signatures are induced in both mouse intestinal inflammation and human ulcerative colitis. Importantly, PGLYRP1 activation by GMTriP-K can result in the protection of mice from TNBS-induced colitis. Mammalian PGLYRPs can function as intracellular pattern recognition receptors for the control of host defense responses in the intestine.

Abstract Clear cell renal cell carcinoma (ccRCC), a metabolic disease originating from renal proximal convoluted tubule (PCT) epithelial cells, remains incompletely understood in terms of its initiating signaling events. Here, we identify γ-butyrobetaine hydroxylase 1 (BBOX1), a key enzyme in carnitine synthesis predominantly expressed in PCT cells, as a tumor suppressor in ccRCC. BBOX1 expression is lost during ccRCC malignant transformation, and its restoration reduces cell viability in physiological medium and inhibits xenograft tumor growth. Transcriptomic analyses reveal that BBOX1 suppresses critical metabolic pathways including mTORC1 signaling and glycolysis in ccRCC. Further, we identify TANK-binding kinase 1 (TBK1) as an essential mediator of mTORC1 and glycolysis activation and as a target of BBOX1-mediated tumor suppression. Mechanistically, BBOX1 disrupts TBK1 activation by preventing its interaction with the upstream activator doublecortin-like kinase 2 (DCLK2). This BBOX1-DCLK2-TBK1 axis unveils an important mechanism in ccRCC metabolic dysregulation and highlights potential therapeutic strategies.

Abstract Background Scrophulariae Radix, the dried root of Scrophularia ningpoensis Hemsl., belongs to the Scrophulariaceae family and is known for its diverse pharmacological effects, such as antihypertensive, anti-inflammatory, and antitumor properties. It is common that the Scrophulariae Radix is often contaminated by various adulterants like S. buergeriana, S. kakudensis, and S. yoshimurae in its medicinal usage. However, traditional methods for identifying Chinese medicinal materials have been found to be insufficient in accurately distinguishing S. ningpoensis from the three adulterant species. Results In this study, RAD-seq technology was employed to sequence 27 individuals from the four species, yielding 55,250 high-quality SNP sites. Genetic differentiation analysis using these sites revealed significant genetic divergence between S. ningpoensis and the three adulterants. Through assessment genetic structure, principal component, and phylogenetic analysis, these four species were effectively distinguished with a high degree of confidence. The phylogenetic results indicated that S. ningpoensis is more closely related to S. yoshimurae, while S. buergeriana shows a closer relationship with S. kakudensis, providing new reference information for understanding interspecific relationships among the four Scrophularia species. Conclusions This study successfully identified S. ningpoensis and the three adulterants, enriched the genomic information of Scrophularia species, and contributed to a more profound understanding of the evolutionary dynamics within this genus. Furthermore, it offers novel insights and methodologies for the identification of medicinal plants.

Abstract Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes. The analysis of 161,333 cells revealed specific subclusters of epithelial cells that were significantly enriched in metastatic lymph nodes, suggesting pro-metastatic characteristics. Furthermore, stromal cells in the tumor microenvironment, including MMP3+IL24+ fibroblasts, APLN+ endothelial cells, and CXCL12+ pericytes, were implicated in ESCC metastasis through angiogenesis, collagen production, and inflammatory responses. Exhausted CD8+ T cells in a cycling status were notably prevalent in metastatic lymph nodes, indicating their potential role in facilitating metastasis. We identified distinct cell-cell communication networks and specific ligand-receptor pathways. Our findings were validated through a spatial transcriptome map and mIHC. This study enhances our comprehension of the cellular and molecular aspects of metastatic lymph nodes in ESCC patients, offering potential insights into novel therapeutic strategies for these individuals.

Abstract Alkali antimonide semiconductor photocathodes are promising candidates for high-brightness electron sources for advanced accelerators, including free-electron lasers (FEL), due to their high quantum efficiency (QE), low emittance, and high temporal resolution. Two challenges with these photocathodes are (1) the lack of a universal deposition recipe to achieve crystal stoichiometries and (2) their high susceptibility to vacuum contamination, which restricts their operation pressure to ultrahigh vacuums and leads to a short lifetime and low extraction charge. To resolve these issues, it is essential to understand the elemental compositions of deposited photocathodes and correlate them to robustness. Here, we report depth profiles for potassium cesium antimonide photocathodes, which were investigated using synchrotron radiation x-ray photoelectron spectroscopy, and the robustness of those photocathodes. We prepared two types of photocathodes with different potassium contents via sequential thermal evaporation. Depth profiles revealed that the photocathodes with a potassium deficit had excess cesium at the surface, while the ratio of potassium and cesium to antimony decreased rapidly within the film. In contrast, the photocathodes with sufficient potassium had close to the theoretical stoichiometry of K2CsSb at the surface and maintained that stoichiometry for over half the entire film thickness. Both photocathode types had a similar maximum QE at 532 nm; however, exposure to oxygen revealed that the photocathode with a crystalline stoichiometry of K2CsSb maintained QE at one order of magnitude higher pressure compared to its potassium-deficit counterpart. These results highlight the importance of synthesizing potassium cesium antimonide photocathodes with sufficient potassium to achieve the theoretical crystalline stoichiometry for both high QE and improved robustness.

For a class of permanent magnet synchronous motors (PMSM) characterized by strong coupling, significant nonlinearity, load uncertainties, and external disturbances, this paper investigates an extended state observer-based direct model-free adaptive predictive compensation control (ESO-dMFAPCC) method for speed regulation. Initially, a dynamic linearization model of a PMSM system with unknown external disturbances is developed. Subsequently, a novel direct model-free adaptive predictive compensation controller, theoretically equivalent to an ideal controller, is proposed. An extended state observer (ESO) is designed to estimate the state variable, capturing the characteristics of the external disturbance and system uncertainty. On this basis, control gains with online adaptive capabilities are designed to achieve adaptive speed control for the PMSM system. The primary advantage of the proposed control method lies in its novel framework for directly constructing a predictive compensation controller, which simplifies the controller structure design process by reducing it to a parameter-optimization problem. Moreover, utilizing only the PMSM system’s input/output (I/O) data, the proposed ESO-dMFAPCC is purely data-driven and exhibits strong robustness against external disturbances. Furthermore, the stability of the closed-loop PMSM system is rigorously analyzed. Finally, the simulation results demonstrate that, compared to PI control, sliding mode control (SMC), and model-free adaptive predictive control (MFAPC), the proposed method offers superior dynamic performance while significantly enhancing the anti-disturbance capabilities of the PMSM system.

Abstract Background Small cell lung cancer (SCLC) is a lethal and recalcitrant malignancy with early metastases. However, the molecular and cellular mechanisms underlying its aggressive characteristics remain relatively elusive. Methods In this study, we conducted a comprehensive proteomic analysis of 90 primary tumors, 15 patient-matched lymph node metastatic tumors, and 15 brain metastatic tumors derived from a cohort of 105 SCLC patients. The potential mechanism for SCLC metastasis was investigated based on the variety of protein expression profiles. Results Primary tumors were divided into two categories according to the their different protein expression profiles, using metastatic tumors as reference. Proteomic comparisons across different groups revealed that lipid metabolism, especially phospholipid metabolism, and immune response had a critical role in SCLC metastasis. Additionally, it was shown that high- and low-density lipoprotein cholesterol were both independent prognostic factors for disease free survival of SCLC patients. To identify critical regulators of metastasis in SCLC, support vector machine was adopted to generate a biomarker combination of ten proteins, all of which significantly correlated with the infiltration of immune cells. Furthermore, it was demonstrated that high expression of phospholipase A2 group IIA in stroma was associated with delayed disease recurrence in limited stage SCLC. Conclusions This study highlighted the critical significance of lipid metabolism, especially phospholipid metabolism in the disease recurrence and metastasis of SCLC.

Abstract The Layered Composite Roof Structure (LCRS) is a common bearing structure consisting of multiple layers of rock above a coal seam, and the energy stored in this structure plays an important role in the occurrence of rockburst. Few studies have been conducted on the theoretical modeling of energy storage in LCRS. This study theoretically developed a bending energy storage model for LCRS under three conditions, and the theoretical model was verified by simulation and experimental data. The results show that the established model can quantify the stress and bending strain energy distributions of LCRS. The bending strain energy distribution is closely related to the position of the neutral axis and the presence of a thick hard layer. When the neutral axis is located in the lower rock beam, it will store more bending strain energy, and the energy stored in LCRS with a thick hard layer before fracture is greater than that without. The distribution rule of stress and strain energy density in the theoretical model basically corresponds to the numerical simulation results, and the errors between five of the six experimental results and the theoretical model proposed in this study were below 7%.

Abstract. Objective:. Eosinophils (EOS) are inflammatory innate immune cells that play an important role in arterial thrombogenesis. There is a paucity of data on whether EOS levels have an impact on long-term outcomes following ST-segment elevation myocardial infarction (STEMI). This study aimed to investigate the impact of EOS count on the clinical outcomes of STEMI patients who underwent emergency percutaneous coronary intervention (PCI). Methods:. This is a retrospective multicenter cohort study. A total of 754 patients with STEMI who required emergency PCI at 5 centers were screened between October 2015 and November 2016. Patients were divided into 2 groups based on EOS count: EOS count

The sweet aromas of red jujube extracts and caramel products are similar, and their reactions could bring synergistic flavors. However, the reaction conditions and the characteristic flavor compounds involved are not well known. In this study, the Maillard reaction was performed using red jujube extracts and glucose caramel products. The reaction factors, such as reaction temperature, reaction time, initial pH, and sample-to-solvent ratio, were optimized by the analysis of sensory scores, total flavor compound (TFC) content, and UV absorption at 420 nm. The optimization of the above factors was further performed by response surface methodology, and antioxidant activities were investigated. Single-factor optimization suggested that the preferred conditions for the Maillard reaction were a temperature of 120°C, a reaction duration of 80 min, an initial pH of 8.0, and a sample-to-solvent ratio of 7:1 (jujube extract: caramel product = 7:1). According to the response surface model, the influence of four factors on the TFC content decreased in the following order: reaction temperature > reaction time > sample-to-solvent ratio > initial pH. The optimal conditions were further established according to the response surface model. GC-MS analysis suggested that the TFC content of Maillard products under the optimized conditions increased by 30.8% compared with those of the unreacted samples. The characteristic flavor compounds in the Maillard products were furfuryl alcohol, 3,5-dihydroxy-2-methyl-4H-pyran-4-one (DDMP), and 5-hydroxymethylfurfural (5-HMF), with the contents of 44.68, 176.26, and 139.75 µg/g, respectively. Moreover, the reaction products exhibited potent antioxidant effects.

Brain imaging genetics is an evolving neuroscience topic aiming to identify genetic variations related to neuroimaging measurements of interest. Traditional linear regression methods have shown success, but their reliance on individual-level imaging and genetic data limits their applicability. Herein, we proposed S-GsMTLR, a group sparse multi-task linear regression method designed to harness summary statistics from genome-wide association studies (GWAS) of neuroimaging quantitative traits. S-GsMTLR directly employs GWAS summary statistics, bypassing the requirement for raw imaging genetic data, and applies multivariate multi-task sparse learning to these univariate GWAS results. It amalgamates the strengths of conventional sparse learning methods, including sophisticated modeling techniques and efficient feature selection. Additionally, we implemented a rapid optimization strategy to alleviate computational burdens by identifying genetic variants associated with phenotypes of interest across the entire chromosome. We first evaluated S-GsMTLR using summary statistics derived from the Alzheimer's Disease Neuroimaging Initiative. The results were remarkably encouraging, demonstrating its comparability to conventional methods in modeling and identification of risk loci. Furthermore, our method was evaluated with two additional GWAS summary statistics datasets: One focused on white matter microstructures and the other on whole brain imaging phenotypes, where the original individual-level data was unavailable. The results not only highlighted S-GsMTLR's ability to pinpoint significant loci but also revealed intriguing structures within genetic variations and loci that went unnoticed by GWAS. These findings suggest that S-GsMTLR is a promising multivariate sparse learning method in brain imaging genetics. It eliminates the need for original individual-level imaging and genetic data while demonstrating commendable modeling and feature selection capabilities.

The long-term stability of the cast-in-place footings in permafrost regions has received much attention due to its climate sensitivity. The current research lacks long-term data validation, especially in the context of climate change. Based on the 13-year (2011–2023) temperature and deformation monitoring data from the Qinghai‒Tibet Power Transmission Line, this study investigates the characteristics of permafrost variation and its impact on the stability of tower footings under the cooling effect from thermosyphons. The results reveal that the thermosyphons effectively reduce the ground temperature around the footings. After the first freeze‒thaw cycle, the soil around the tower footings completed refreezing and maintained a frozen state. In the following 13 years, the ground temperature continued to decrease due to the cooling effect of thermosyphons. The duration notably exceeded the previously predicted 5 years. The temperature reduction at the base of the footings corresponded well with the frost jacking of the tower footings and could be divided into three distinct phases. In phase 1, the ground temperature around the footings rapidly reduced, approaching that of the natural field, while the footings experienced pronounced deformation. In phase 2, the ground temperature decreased at a faster rate, and the deformation rate of the footings slowed down. In phase 3, the frost jacking of the footings gradually retarded with the decrease in base temperature. Additionally, the ground temperature differences of over 1 °C were observed among different tower footings, which may lead to the differential deformation among the tower footings. The ground temperature differentiation is attributed to the difference in solar radiation intensity, which is shaded by the tower structure from different directions. This study provides theoretical support and empirical accumulation for the construction and maintenance of tower footings in permafrost regions.

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.

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.

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.

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.

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.

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 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.

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 Mass spectrometry imaging (MSI) provides valuable insights into metabolic heterogeneity by capturing in situ molecular profiles within organisms. One challenge of MSI heterogeneity analysis is performing an objective segmentation to differentiate the biological tissue into distinct regions with unique characteristics. However, current methods struggle due to the insufficient incorporation of biological context and high computational demand. To address these challenges, a novel deep learning‐based approach is proposed, GraphMSI, which integrates metabolic profiles with spatial information to enhance MSI data analysis. Our comparative results demonstrate GraphMSI outperforms commonly used segmentation methods in both visual inspection and quantitative evaluation. Moreover, GraphMSI can incorporate partial or coarse biological contexts to improve segmentation results and enable more effective three‐dimensional MSI segmentation with reduced computational requirements. These are facilitated by two optional enhanced modes: scribble‐interactive and knowledge‐transfer. Numerous results demonstrate the robustness of these two modes, ensuring that GraphMSI consistently retains its capability to identify biologically relevant sub‐regions in complex practical applications. It is anticipated that GraphMSI will become a powerful tool for spatial heterogeneity analysis in MSI data.

ObjectiveTo build a new prognostic risk assessment model based on immune cell co-expression networks for predicting overall survival and evaluating the efficacy of immunotherapy for colon cancer patients.MethodsThe Cancer Genome Atlas (TCGA) database was used to obtain mRNA expression profiling data, clinical information, and somatic mutation data from colorectal cancer patients. The degree of tumor immune cell infiltration of the samples was analyzed using the CIBERSORT algorithm. Co-expression of immune-related genes was analyzed using weighted correlation network analysis (WGCNA) and gene modules were identified. Prognosis-related genes were screened and models were constructed using LASSO-Cox analysis. The models were validated by survival analysis. The prognostic potential of the models was quantitatively assessed using Cox regression analysis and the development of column line plots. Immunotherapy sensitivity analysis was performed using CIBERSORT and TIMER algorithms. Gene biofunction analysis was performed using Gene set enrichment analysis (GSEA) and Gene set variation analysis (GSVA). And the chemotherapeutic response to different drugs was assessed.ResultsWe established a novel prognostic model utilizing the WGCNA method, which demonstrated robust predictive accuracy for patient survival. The high-risk subgroup in our model exhibited elevated immune cell infiltration coupled with a higher tumor mutation burden, but the difference in response to immunotherapy was not significant compared to the low-risk group. Furthermore, we identified distinct chemotherapy responses to 39 drugs between these risk subgroups.ConclusionThis study revealed a significant correlation between high levels of immune infiltration and unfavorable prognosis in patients with colon cancer. Furthermore, an accurate prognostic risk prediction model based on the co-expression of relevant genes by immune cells was developed, enabling precise prediction of survival of colon cancer patients. These findings offer valuable insights for accurate prognostication and comprehensive management of individuals diagnosed with colon cancer.

Biological nanotechnologies based on functional nanoplatforms have synergistically catalyzed the emergence of cancer therapies. As a subtype of metal-organic frameworks (MOFs), zeolitic imidazolate frameworks (ZIFs) have exploded in popularity in the field of biomaterials as excellent protective materials with the advantages of conformational flexibility, thermal and chemical stability, and functional controllability. With these superior properties, the applications of ZIF-based materials in combination with various therapies for cancer treatment have grown rapidly in recent years, showing remarkable achievements and great potential. This review elucidates the recent advancements in the use of ZIFs as drug delivery agents for cancer therapy. The structures, synthesis methods, properties, and various modifiers of ZIFs used in oncotherapy are presented. Recent advances in the application of ZIF-based nanoparticles as single or combination tumor treatments are reviewed. Furthermore, the future prospects, potential limitations, and challenges of the application of ZIF-based nanomaterials in cancer treatment are discussed. We except to fully explore the potential of ZIF-based materials to present a clear outline for their application as an effective cancer treatment to help them achieve early clinical application.

The use of combination therapies that employ a variety of cell death mechanisms has emerged as a promising avenue of research in the treatment of cancer. However, the optimization of therapeutic synergies when integrating different modes remains a significant challenge. To this end, we developed a multifunctional intelligent drug-carrying nanoparticle (DFMTCH NPs) based on the metal-organic framework MIL-100, loaded with doxorubicin (DOX) and disulfiram (DSF), coated with a Cu-tannic acid (Cu-TA) network and hyaluronic acid (HA), for the purpose of combined chemotherapy/chemodynamic/photothermal anti-cancer therapy. On the one hand, the DFMTCH NPs exhibited a range of therapeutic capabilities, including chemotherapy, photothermal therapy (PTT), and chemodynamic therapy (CDT), which collectively enhanced the anti-tumor efficacy of chemotherapeutic agents. In addition, DFMTCH NPs proved sensitive photoacoustic imaging (PAI) in image-guided therapy. On the other hand, DFMTCH NPs could produce reactive oxygen species (ROS) and consume glutathione (GSH) by amplifying cellular oxidative stress, while causing intracellular mitochondrial dysfunction, inducing effective cuproptosis/ferroptosis/apoptosis to inhibit tumor growth. Collectively, this work provided an innovative strategy for designing multifunctional nanoparticles for effective combination therapies to combat colorectal cancer (CRC).

As emerging contaminants growing threat to aquatic organisms, explore effective mitigation strategies is particularly important. Our previous studies have shown that selenium-rich Bacillus subtilis can not only alleviate the cause of brain damage by perfluorohexanoic acid (PFHxA) in Carassius auratus via the intestinal axis of the brain, but its metabolites can also alleviate PFHxA toxicity. This study further explores the potential mechanism through in vitro experiments. Findings demonstrate that apoptosis caused by PFHXA is effectively reduced with the use of selenium-rich Bacillus subtilis, which operates through the BDNF/PI3K/AKT/GSK-3β signalling pathway. Furthermore, utilisation of LY294002 and LICl inhibitors provided additional confirmation of the pivotal function of this pathway in neuroprotection. Our study results emphasize the significance of the PI3K/AKT/GSK-3β signalling pathway in promoting neuronal survival. Additionally, our findings establish a novel theoretical framework for using selenium-enriched Bacillus subtilis in environmental toxicology. Selenium-enriched Bacillus subtilis can be used as a novel microecological preparation. Implementing this approach could effectively counteract neurotoxic consequences of emerging contaminants, hence safeguarding and preserving aquatic ecosystems.

Mitochondria, recognized as the "powerhouse" of cells, play a vital role in generating cellular energy through dynamic processes such as fission and fusion. Viruses have evolved mechanisms to hijack mitochondrial function for their survival and proliferation. Here, we report that infection with the swine arterivirus porcine reproductive and respiratory syndrome virus (PRRSV), manipulates mitochondria calcium ions (Ca2+) to induce mitochondrial fission and mitophagy, thereby reprogramming cellular energy metabolism to facilitate its own replication. Mechanistically, PRRSV-induced mitochondrial fission is caused by elevated levels of mitochondria Ca2+, derived from the endoplasmic reticulum (ER) through inositol 1,4,5-triphosphate receptor (IP3R)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial calcium uniporter (MCU) channels. This process is associated with increased mitochondria-associated membranes (MAMs), mediated by the upregulated expression of sigma non-opioid intracellular receptor 1 (SIGMAR1). Elevated mitochondria Ca2+ further activates the Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-AMP-activated protein kinase (AMPK)-dynamin-related protein 1 (DRP1) signaling pathway, which interacts with mitochondrial fission protein 1 (FIS1) and mitochondrial dynamics proteins of 49 kDa (MiD49) to promote mitochondrial fission. PRRSV infection, alongside mitochondrial fission, triggers mitophagy via the PTEN-induced putative kinase 1 (PINK1)-Parkin RBR E3 ubiquitin (Parkin) pathway, promoting cellular glycolysis and excessive lactate production to facilitate its own replication. This study reveals the mechanism by which mitochondrial Ca2+ regulates mitochondrial function during PRRSV infection, providing new insights into the interplay between the virus and host cell metabolism.

Background Mrp 8/14 is abundantly secreted by activated neutrophils during infection and inflammation. However, its prognostic value in acute respiratory distress dyndrome (ARDS) induced by sepsis is poorly understood. Our aim was to investigate the relationship between serum Mrp 8/14 and the prognosis in sepsis-induced ARDS patients admitted to the intensive care unit (ICU). Methods Serum Mrp 8/14 concentrations were analyzed in 118 ARDS patients induced by sepsis included in the analytical study. Patients were enrolled upon admission to the ICU of Nanjing Hospital affiliated to Nanjing Medical University. The baseline information and clinical outcomes were obtained. Patients were divided into survivor group and non-survivor group according to whether they died during ICU hospitalization. Results The serum Mrp 8/14 levels were significantly increased in the non-survivor group compared to the survivor group (P < 0.05). Logistic regression analysis showed that serum Mrp 8/14, albumin and APACHE II were the independent factors for predicting the prognosis of sepsis-induced ARDS during ICU hospitalization after adjustment. Additionally, the area under the receiver operating characteristic curve for Mrp 8/14 combined with albumin was associated with ICU mortality and was higher than that of Mrp 8/14, albumin, APACHE II and Mrp 8/14 combined with APACHE II (all P < 0.05). A nomogram was constructed to predict ICU mortality and the c-indexes of predictive accuracy was 0.830 in the cohort (P < 0.05). Conclusions The serum Mrp 8/14 upon ICU admission in septic patients may be useful for predicting mortality in sepsis-induced ARDS patients during ICU hospitalization.

ABSTRACT The interaction between Z-DNA binding protein 1 (ZBP1) and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been uncovered in several viral infections. However, the role of this molecular pathway during infection with the alpha-herpesvirus pseudorabies virus (PRV) remains largely elusive. Here, we report that during PRV infection, ZBP1-mediated NLRP3 inflammasome activation is inhibited by the viral tegument protein VP22, thereby facilitating viral infection. Through a combination of RNA sequencing and genetic studies, we demonstrate that PRV VP22 functions as a virus-encoded virulence factor by evading the inhibitory effects of ZBP1 on virus infection. Importantly, the replication and pathogenicity of a recombinant PRV lacking VP22 are significantly increased in ZBP1-deficient cells and mice. Mechanistically, PRV VP22 interacts with ZBP1, impeding the recruitment of receptor-interacting protein kinase 3 and Caspase-8, thereby inhibiting NLRP3 activation. Furthermore, we show that the N-terminal 1–50 amino acid domain of VP22 dominantly destabilizes ZBP1-mediated function. Taken together, these findings identify a functional link between PRV infection and ZBP1-mediated NLRP3 inflammatory response, providing novel insights into the pathogenesis of PRV and other herpesviruses.IMPORTANCEZ-DNA binding protein 1 (ZBP1) functions as a pivotal innate immune sensor that regulates inflammatory cell death during viral infections. However, its role in pseudorabies virus (PRV) infection remains unknown. Here, we demonstrate that ZBP1 serves as a restrictive factor by triggering the activation of the NLR family pyrin domain-containing 3 inflammasome, a process counteracted by PRV-encoded protein VP22. Furthermore, VP22 interferes with the interaction between ZBP1 and receptor-interacting protein kinase 3/Caspase-8, particularly through its N-terminal 1–50 amino acids. Importantly, deficiency in ZBP1 enhances the replication and virulence of recombinant viruses lacking VP22 or its N-terminal 1–50 amino acids. These findings reveal how PRV escapes ZBP1-mediated inflammatory responses during infection, potentially informing the rational design of therapeutic interventions.

ObjectiveTo evaluate postoperative cerebral perfusion changes and their influencing factors in carotid endarterectomy (CEA) patients by integrating multimodal monitoring methods, including cerebral regional oxygen saturation (rSO2), carotid ultrasound (CU), computed tomographic angiography (CTA), and computed tomographic perfusion imaging (CTP), with computational fluid dynamics (CFD) assessment.MethodsWe conducted a cohort study on patients with internal carotid artery (ICA) stenosis undergoing CEA at our institution. Pre- and postoperative assessments included CU, CTA, CTP, and rSO2 monitoring. Hemodynamic parameters recorded were mean flow velocity (MFV), peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI), rSO2, and cerebral blood flow (CBF). CFD quantified the total pressure (TP), wall shear stress (WSS), wall shear stress ratio (WSSR), and translesional pressure ratio (PR) of the ICA. Pearson correlation was used to analyze factors influencing cerebral perfusion changes. Multivariate logistic regression identified risk factors for cerebral hyperperfusion (CH). The predictive value of multimodal and single-modality monitoring for CH was evaluated using ROC curve analysis.ResultsFifty-six patients were included, with nine developing postoperative CH. CU showed significant reductions in MFV, PSV, EDV, and RI of the ICA (p

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.

Anchor cables in water-rich roadways frequently experience severe corrosion and resultant fractures due to the combined effects of mine water and high stress. However, the precise factors influencing corrosion on these cables remain ambiguous, presenting challenges to roadway support safety. This study investigated the impact of major ions present in weakly alkaline mine water on anchor cable corrosion using salt spray corrosion experiments. The results indicated that major anions such as Cl- notably influence anchor cable corrosion, which primarily manifested as pitting corrosion. The nominal yield strength decreased by 95.68–156.01 MPa, and the nominal tensile strength decreased by 133.44–202.77 MPa because of a decrease in the cross-sectional area. During the corrosion process, major anions such as Cl- continuously degraded the passivation film on the surface of the anchor cable, exposing its internal metal structure and exacerbating corrosion until eventual fracture failure occurred. Therefore, this paper proposes a corrosion protection technique for mine anchor cables to realize superior protective effects compared to conventional anchor cables used concurrently in field applications.

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.

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 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

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 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 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 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.

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 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 seabed surface is an important boundary for ocean exploration and foundation for ocean engineering construction. Accurate acquisition of seabed sediment mechanical properties and environmental parameters is critical to the development of marine resources and marine engineering. In this study, by designing the Seabed Cone Penetration Test (CPT) and Sampling System, multiparameter in situ testing and low-disturbance sampling of 3,000-m deep-sea seabed sediments are performed. Accounting for the stable penetration speed of the probe rod is the basis for ensuring the accuracy of the static penetration test results. The system adopts electrohydraulic proportional position control and a fuzzy proportional integral derivative (PID) controller to precisely control the position of the piston of the hydraulic circuit, which can improve the accuracy of the cone test data and reduce the interference of the sampling tube with the original sediment during the sampling process. Moreover, electrohydraulic co-simulation of the hydraulic control system was conducted with the AMESim and Simulink software, and the position control and speed control effects of the system were verified. The entire system was tested on site in the Shenhu Sea area of the South China Sea. This test successfully obtained nine in situ parameters, including physical and chemical parameters, for sediments within a depth range of 2.66 m on the seabed surface at a depth of 1,820 m. This system accurately and efficiently reflects the property characteristics of seafloor sediments in an in situ environment and can be widely used in marine engineering geological investigations.