Localization and Tissue Tropism of Ostreid Herpesvirus 1 in Blood Clam Anadara broughtonii.

OsHV-1 caused detrimental infections in a variety of bivalve species of major importance to aquaculture worldwide. Since 2012, there has been a notable increase in the frequency of mass mortality events of the blood clam associated with OsHV-1 infection. The pathological characteristics, tissue and cellular tropisms of OsHV-1 in A. broughtonii remain unknown. In this study, we sought to investigate the distribution of OsHV-1 in five different organs (mantle, hepatopancreas, gill, foot, and adductor muscle) of A. broughtonii by quantitative PCR, histopathology and in situ hybridization (ISH), to obtain insight into the progression of the viral infection. Our results indicated a continuous increase in viral loads with the progression of OsHV-1 infection, reaching a peak at 48 h or 72 h post-infection according to different tissues. Tissue damage and necrosis, as well as colocalized OsHV-1 ISH signals, were observed primarily in the connective tissues of various organs and gills. Additionally, minor tissue damage accompanied by relatively weak ISH signals was detected in the foot and adductor muscle, which were filled with muscle tissue. The predominant cell types labeled by ISH signals were infiltrated hemocytes, fibroblastic-like cells, and flat cells in the gill filaments. These results collectively illustrated the progressive alterations in pathological confusion and OsHV-1 distribution in A. broughtonii, which represent most of the possible responses of cells and tissues to the virus.

Parathyroid hormone mediates the adverse impact of air pollution exposure on serum 25-hydroxyvitamin D: A nationwide cross-sectional study in China.

BACKGROUND: Maintaining normal levels of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) is crucial for preserving skeletal health. However, evidence regarding the associations of exposure to air pollution with serum 25(OH)D and PTH were limited and ambiguous. Hence, the objective of this cross-sectional study was to systematically evaluate the association between air pollution (particulate matter ≤ 2.5 µm [PM2.5] and ozone [O3]) exposure and serum 25(OH)D and PTH levels in males aged 50 and above and postmenopausal female. MATERIALS AND METHODS: This study is multicenter, cross-sectional study within the framework of the ongoing China Community-based Cohort of Osteoporosis. The 1-year-average PM2.5 and O3 exposures prior to the baseline survey were estimated using random forest models with relatively high accuracy. Multiple linear regression models were employed to assess the associations between PM2.5 and O3 concentrations with the serum levels of 25(OH)D and PTH. Furthermore, mediation analysis was performed to scrutinize the potential mediating role of PTH in the interplay between PM2.5, O3, and serum 25(OH)D. RESULTS: A total of 13,194 participants were included. Our analysis showed that every 10 µg/m3 increase in the 1-year average PM2.5, were associated with -0.32 units (95% CI: -0.48, -0.17) of change in the 25(OH)D and 0.15 units (95% CI: 0.11, 0.19) of change in the PTH, respectively. Every 10 µg/m3 increase in the 1-year average O3, were associated with -0.78 units (95% CI: -1.05, -0.51) of change in the 25(OH)D and 0.50 units (95% CI: 0.43, 0.57) of change in the PTH, respectively. Estimates of the mediation ratio indicated that increased PTH mediated a 50.48% negative correlation between PM2.5 exposure and circulating 25(OH)D level. Increased PTH mediated 69.61% of the negative effects of O3 exposure on circulating 25(OH)D level. CONCLUSIONS: Exposure to PM2.5 and O3 significantly diminished 25(OH)D while elevating PTH levels. Notably, the elevated PTH concentration partially mediates the associations between PM2.5 and O3 exposure and 25(OH)D level.

Comparing Carotid Artery Velocities with Current ASCVD Risk Stratification: A Novel Approach to Simpler Risk Assessment.

PURPOSE: To explore the potential of a novel approach to simplify risk assessment by comparing carotid artery velocities with current atherosclerotic cardiovascular disease (ASCVD) risk stratification method using nonlinear measurements. METHODS: In this prospective study conducted at a medical center in southern Taiwan from January 1, 2020, to December 31, 2021, 1636 participants aged 40-75 years without prior ASCVD events were enrolled. Carotid flow velocity was obtained through duplex ultrasonography. ASCVD risk was categorized into two groups according to the 2022 USPSTF guidelines for primary prevention. We analyzed associations between flow indices and ASCVD risk using logistic regression and generalized additive models (GAMs). RESULTS: The end diastolic velocity (EDV) of common carotid artery (CCA) and the peak systolic velocity (PSV) of internal carotid artery (ICA) were inversely and nonlinearly associated with cardiovascular event risk. Multivariate logistic regression analysis with ROC curves revealed that the optimal speed for the EDV of CCA was approximately 23.75 cm/s, and the optimal PSV and EDV of ICA were approximately 81.75 cm/s and 26.75 cm/s, respectively. The GAMs showed U-shaped relationships between elevated ASCVD risk and blood flow velocity in the carotid arteries, with inflection points of approximately 82 cm/s in the PSV of ICA and near 25 cm/s in the EDV of CCA. Both methods revealed similar results. CONCLUSIONS: The EDVs and PSVs of the CCA and ICA are associated with the development of cardiovascular events. Optimal velocity ranges were identified; however, further hemodynamic investigations are warranted.

Cooperative Diarylborinic Acid/Chloride-Catalyzed Formal SNi Reaction of cis-4-Hydroxymethyl-1,2-Cyclopentene Oxides.

A catalytic formal SNi reaction was designed to achieve stereoretentive products for cis-4-hydroxymethyl-1,2-cyclopentene oxides by using diarylborinic acid as a dual role catalyst and chloride as a catalytic transient nucleophile through a double-displacement mechanism. This reaction offers the advantages of a low catalyst loading of 0.1 mol % and wide substrate scope, even including N-substituents. The use of chiral boron acid as a catalyst for this reaction was also attempted.

Survival benefit of sequential curative treatment for TACE suitable BCLC stage B HCC patients.

To clarify the survival benefit of sequential curative treatment post transcatheter arterial chemoembolization (TACE) for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), we retrospectively analyzed HCC patients at a hospital. From July 2017 to July 2020, 787 treatment-naïve HCC patients underwent initial treatment; 77 (9.8%) meeting inclusion criteria were enrolled. Their initial treatments were TACE only (n = 68, 88.3%) or TACE with other treatments (n = 9, 11.7%). Median survival of the TACE-only group was 30 months. Treatment response was evaluated after 2 or 3 consecutive TACEs for patients (54/68, 79.4%) with available pre-/post-TACE computerized tomography (CT) or magnetic resonance imaging (MRI). Treatment responses was divided into 4 groups: complete (n = 14, 26%, group (Gr) 1), incomplete without new tumor growth (n = 28, 52.0%, Gr2), incomplete with new growth (n = 6, 11%, Gr3), and progression (n = 6, 11%, Gr4). Of Gr2, further treatment after TACE were had radiofrequency ablation (n = 13, Gr2a), TACE (n = 9, Gr2b), other modalities (n = 6, Gr2c. Gr2a's median survival was longer than Gr2b's (> 60 vs. 20 months, p = 0.007). Nine patients in Gr2a (69%, 9/13) achieved a complete response, but none in Gr2b (p = 0.001). Conclusively, in TACE-suitable BCLC stage B HCC patients, a partial response without new tumor growth can serve as an indicator of treatment effectiveness following initial TACE treatment. This can facilitate the selection of appropriate candidates to receive RFA, potentially resulting in improved patient survival.

Causal association between B cell count and psoriasis using two-sample Mendelian randomization.

To investigate the causality between B cell count and psoriasis by Mendelian randomization (MR). Collected B cell count and psoriasis data from IEU Open GWAS Project. Employed inverse variance weighting (IVW), MR-Egger, WM, weighted mode for analysis, ensuring result robustness. Assessed horizontal pleiotropy with MR-Egger, detected outliers using MR-PRESSO and examined instrumental variables heterogeneity with Cochran's Q-test. The IVW method suggested an association between a genetically predicted memory B cell count and the risk of psoriasis vulgaris. IVW results also showed no causality between other exposure factors and the corresponding outcomes. Also, the global test of MR-PRESSO analysis showed a significant association between a genetically predicted transitional absolute B cell count and the lower risk of psoriasis vulgaris. MR-Egger regression showed that horizontal pleiotropy did not influence the analysis results. We found that memory B cell absolute counts are associated with a lower risk of psoriasis. These data further elucidate the role of memory B cells in psoriasis and provide new options for psoriasis treatment.

A narrative review of the measurement methods for biomechanical properties of plantar soft tissue in patients with diabetic foot.

This article provides an overview of the development history and advantages and disadvantages of measurement methods for soft tissue properties of the plantar foot. The measurement of soft tissue properties is essential for understanding the biomechanical characteristics and function of the foot, as well as for designing and evaluating orthotic devices and footwear. Various methods have been developed to measure the properties of plantar soft tissues, including ultrasound imaging, indentation testing, magnetic resonance elastography, and shear wave elastography. Each method has its own strengths and limitations, and choosing the most appropriate method depends on the specific research or clinical objectives. This review aims to assist researchers and clinicians in selecting the most suitable measurement method for their specific needs.

Production of γ-aminobutyric acid by immobilization of two Yarrowia lipolytica glutamate decarboxylases on electrospun nanofibrous membrane.

This study harnesses glutamate decarboxylase (GAD) from Yarrowia lipolytica to improve the biosynthesis of γ-aminobutyric acid (GABA), focusing on boosting the enzyme's catalytic efficiency and stability by immobilizing it on nanofibrous membranes. Through recombinant DNA techniques, two GAD genes, YlGAD1 and YlGAD2, were cloned from Yarrowia lipolytica and then expressed in Escherichia coli. Compared to their soluble forms, the immobilized enzymes exhibited significant improvements in thermal and pH stability and increased resistance to chemical denaturants. The immobilization notably enhanced substrate affinity, as evidenced by reduced Km values and increased kcat values, indicating heightened catalytic efficiency. Additionally, the immobilized YlGAD1 and YlGAD2 enzymes showed substantial reusability, maintaining 50% and 40% of their activity, respectively, after six consecutive cycles. These results underscore the feasibility of employing immobilized YlGAD enzymes for cost-effective and environmentally sustainable GABA production. This investigation not only affirms the utility of YlGADs in GABA synthesis but also underscores the advantages of enzyme immobilization in industrial settings, paving the way for scalable biotechnological processes.

Targeting PD-1/PD-L1 in tumor immunotherapy: Mechanisms and interactions with host growth regulatory pathways.

Tumor immunotherapy has garnered considerable attention, emerging as a new standard of care in cancer treatment. The conventional targets, such as VEGF and EGFR, have been extended to others including BRAF and PD-1/PD-L1, which have shown significant potential in recent cancer treatments. This review aims to succinctly overview the impact and mechanisms of therapies that modulate PD-1/PD-L1 expression by targeting VEGF, EGFR, LAG-3, CTLA-4 and BRAF. We investigated how modulation of PD-1/PD-L1 expression impacts growth factor signaling, shedding light on the interplay between immunomodulatory pathways and growth factor networks within the tumor microenvironment. By elucidating these interactions, we aim to provide insights into novel potential synergistic therapeutic strategies for cancer immunotherapy.

Novel machine-learning prediction tools for overall survival of patients with chondrosarcoma: Based on recursive partitioning analysis.

BACKGROUND: Chondrosarcoma (CHS), a bone malignancy, poses a significant challenge due to its heterogeneous nature and resistance to conventional treatments. There is a clear need for advanced prognostic instruments that can integrate multiple prognostic factors to deliver personalized survival predictions for individual patients. This study aimed to develop a novel prediction tool based on recursive partitioning analysis (RPA) to improve the estimation of overall survival for patients with CHS. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed, including demographic, clinical, and treatment details of patients diagnosed between 2000 and 2018. Using C5.0 algorithm, decision trees were created to predict survival probabilities at 12, 24, 60, and 120 months. The performance of the models was assessed through confusion scatter plot, accuracy rate, receiver operator characteristic (ROC) curve, and area under ROC curve (AUC). RESULTS: The study identified tumor histology, surgery, age, visceral (brain/liver/lung) metastasis, chemotherapy, tumor grade, and sex as critical predictors. Decision trees revealed distinct patterns for survival prediction at each time point. The models showed high accuracy (82.40%-89.09% in training group, and 82.16%-88.74% in test group) and discriminatory power (AUC: 0.806-0.894 in training group, and 0.808-0.882 in test group) in both training and testing datasets. An interactive web-based shiny APP (URL: https://yangxg1209.shinyapps.io/chondrosarcoma_survival_prediction/) was developed, simplifying the survival prediction process for clinicians. CONCLUSIONS: This study successfully employed RPA to develop a user-friendly tool for personalized survival predictions in CHS. The decision tree models demonstrated robust predictive capabilities, with the interactive application facilitating clinical decision-making. Future prospective studies are recommended to validate these findings and further refine the predictive model.

Pyrazolone-Protein Interaction Enables Long-Term Retention Staining and Facile Artificial Biorecognition on Cell Membranes.

Cell membrane genetic engineering has been utilized to confer cell membranes with functionalities for diagnostic and therapeutic purposes but concerns over cost and variable modification results. Although nongenetic chemical modification and phospholipid insertion strategies are more convenient, they still face bottlenecks in either biosafety or stability of the modifications. Herein, we show that pyrazolone-bearing molecules can bind to proteins with high stability, which is mainly contributed to by the multiple interactions between pyrazolone and basic amino acids. This new binding model offers a simple and versatile noncovalent approach for cell membrane functionalization. By binding to cell membrane proteins, pyrazolone-bearing dyes enabled precise cell tracking in vitro (>96 h) and in vivo (>21 days) without interfering with the protein function or causing cell death. Furthermore, the convenient anchor of pyrazolone-bearing biotin on cell membranes rendered the biorecognition to avidin, showing the potential for artificially creating cell targetability.

Application of Electrophysiological Techniques in Assessing of Neuromuscular Junction-Related Disorders.

This review aims to comprehensively summarize the application of electrophysiological methods, specifically repetitive nerve stimulation (RNS) and single fiber electromyography (SFEMG), in the diagnosis of neuromuscular junction (NMJ) disorders, including myasthenia gravis, Lambert-Eaton syndrome, and sarcopenia in the elderly. Both RNS and SFEMG have demonstrated high sensitivity and specificity in detecting NMJ abnormalities. RNS aids in distinguishing presynaptic from postsynaptic lesions, while SFEMG provides direct evidence of NMJ function by assessing single motor unit action potentials. Key parameters in SFEMG, such as fiber density, jitter, and pulse blocking, are crucial for evaluating NMJ function. Increased fiber density and jitter value, along with pulse blocking, are often observed in patients with NMJ disorders. However, despite the extensive application of these techniques in various NMJ-related diseases, their role in aging, particularly in sarcopenic patients, remains underexplored, highlighting the need for future research.

Landscape of the Lumbar Cartilaginous End Plate Microbiota and Metabolites in Patients with Modic Changes.

BACKGROUND: Modic changes (MCs), vertebral end plate and bone marrow damage observed by magnetic resonance imaging, are an independent risk factor for low back pain. The compositions of and interaction between microbiota and metabolites in the lumbar cartilaginous end plates (LCEPs) of patients with MCs have not been identified. METHODS: Patients with lumbar disc degeneration who were undergoing lumbar spinal fusion surgery were recruited between April 2020 and April 2021. LCEPs were collected for 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS)-based targeted metabolomic profiling. Of the 54 patients recruited, 24 had no MCs and 30 had changes classified as Modic type 2 or 3. The primary goal was to identify specific genera of microbiota associated with MCs, and secondary goals included investigating differences in metabolites between patients with and without MCs and exploring the correlation between these metabolites and microorganisms. RESULTS: Investigation of the microbiota community structure revealed that both alpha diversity and beta diversity were significantly different between patients with and without MCs, and the abundances of 26 genera were significantly different between these 2 groups. Metabolomic analysis revealed that 26 metabolites were significantly different between the 2 groups. The unsaturated fatty acid pathway was found to be the main pathway related to MCs. Multiomic correlation analysis suggested that Caulobacteraceae (unclassified) and Mycobacterium, Clostridium, Blautia, and Bifidobacterium at the genus level were linked to dysregulation of fatty acid metabolism, contributing to the pathogenesis of MCs. CONCLUSIONS: Our study represents a foundational effort to examine the landscape of the microbiota and metabolites in patients with MCs, informing future studies on the pathogenesis of and targeted therapy for MCs. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Decoding the fish genome opens a new era in important trait research and molecular breeding in China.

Aquaculture represents the fastest-growing global food production sector, as it has become an essential component of the global food supply. China has the world's largest aquaculture industry in terms of production volume. However, the sustainable development of fish culture is hindered by several concerns, including germplasm degradation and disease outbreaks. The practice of genomic breeding, which relies heavily on genome information and genotypephenotype relationships, has significant potential for increasing the efficiency of aquaculture production. In 2014, the completion of the genome sequencing and annotation of the Chinese tongue sole signified the beginning of the fish genomics era in China. Since then, domestic researchers have made dramatic progress in functional genomic studies. To date, the genomes of more than 60 species of fish in China have been assembled and annotated. Based on these reference genomes, evolutionary, comparative, and functional genomic studies have revolutionized our understanding of a wide range of biologically and economically important traits of fishes, including growth and development, sex determination, disease resistance, metamorphosis, and pigmentation. Furthermore, genomic tools and breeding techniques such as SNP arrays, genomic selection, and genome editing have greatly accelerated genetic improvement through the incorporation of functional genomic information into breeding activities. This review aims to summarize the current status, advances, and perspectives of the genome resources, genomic study of important traits, and genomic breeding techniques of fish in China. The review will provide aquaculture researchers, fish breeders, and farmers with updated information concerning fish genomic research and breeding technology. The summary will help to promote the genetic improvement of production traits and thus will support the sustainable development of fish aquaculture.

Incidence and prognostic factors of residual back pain in patients treated for osteoporotic vertebral compression fractures: a systematic review and meta-analysis.

BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common consequence of osteoporosis and can significantly impact the quality of life for affected individuals. Despite treatment options such as vertebroplasty and kyphoplasty, many patients continue to experience residual back pain (RBP) even after the fracture has healed. The incidence of RBP after OVCF treatment varies among studies, and there is a need for further research to understand the risk factors associated with RBP. METHODS: A systematic review and meta-analysis were conducted following the PRISMA guidelines. Electronic databases were searched, and relevant studies were selected based on inclusion and exclusion criteria. Data extraction and quality assessment were performed independently by two authors. Statistical analysis included single-proportion meta-analyses and pooling of odds ratios (OR) using the inverse-variance method, to calculate the overall incidences of RBP and cement leakage and identify risk factors associated with RBP. RESULTS: A total of 19 studies were included in the analysis. The overall incidences of RBP and cement leakage were found to be 16% and 18%, respectively. Several risk factors were identified, including gender, bone mineral density, depression, baseline visual analog scale (VAS) score, intravertebral vacuum cleft, number of fractured segments, cement distribution, history of vertebral fracture, thoracolumbar fascial injury, and fracture non-union. CONCLUSIONS: This study provides potential value within the scope of the incidence and risk factors of RBP following treatment of OVCFs. The identified risk factors can help clinicians identify high-risk patients and tailor appropriate interventions. Future research should focus on standardizing the definition of RBP and patient selection criteria to improve the accuracy of estimates and facilitate better management strategies for OVCF patients.

Association Between Osteoporosis and Adiposity Index Reveals Nonlinearity Among Postmenopausal Women and Linearity Among Men Aged over 50 Years.

PURPOSE: Previous research shows conflicting views on the relationship between obesity and osteoporosis, partly due to variations in obesity classification and the nonlinear nature of these relationships. This study investigated the association between adiposity indices and osteoporosis, diagnosed using dual-energy X-ray absorptiometry (DXA), employing nonlinear models and offering optimal thresholds to prevent further bone mineral density decline. METHODS: In 2019, a prospective study enrolled males over 50 years and postmenopausal women. Anthropometric measurements, blood biochemistry, and osteoporosis measured by DXA were collected. Associations between adiposity indices and osteoporosis were analyzed using a generalized additive model and segmented regression model. RESULTS: The study included 872 women and 1321 men. Indices such as abdominal volume index (AVI), visceral adiposity index (VAI), waist circumference (WC), hip circumference, body mass index (BMI), waist-to-hip ratio, and waist-to-height ratio (WHtR) were inversely associated with osteoporosis. In women, the relationship between the risk of osteoporosis and the adiposity indices was U-shaped, with thresholds of WC = 94 cm, AVI = 17.67 cm2, BMI = 25.74 kg/m2, VAI = 4.29, and WHtR = 0.61, considering changes in bone mineral density. Conversely, men exhibited a linear patterns for the inverse association. CONCLUSION: The impact of obesity and adiposity on osteoporosis varies significantly between women and men. In postmenopausal women, the relationship is nonlinear (U-shaped), with both very low and very high adiposity linked to higher osteoporosis risk. In men over 50, the relationship is linear, with higher adiposity associated with lower osteoporosis risk. The study suggests that maintaining specific levels of adiposity could help prevent osteoporosis in postmenopausal women.

Analysis of the Variation in Antioxidant Activity and Chemical Composition upon the Repeated Thermal Treatment of the By-Product of the Red Ginseng Manufacturing Process.

Steamed ginseng water (SGW) is a by-product of the repeated thermal processing of red ginseng, which is characterized by a high bioactive content, better skin care activity, and a large output. However, its value has been ignored, resulting in environmental pollution and resource waste. In this study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The antioxidant activity (DPPH, ABTS, FRAP, and OH) and chemical composition (total sugars, total saponins, and reducing and non-reducing sugars) were comprehensively evaluated based on the entropy weighting method. Four comparison groups (groups 1 and 3, groups 1 and 5, groups 1 and 7, and groups 1 and 9) were screened for 37 important common difference markers using OPLS-DA analysis. The entropy weight method was used to analyze the weights of the indicators; the seventh SGW sample was reported to have a significant weight. The results of this study suggest that heat treatment time and frequency can be an important indicator value for the quality control of SGW cycling operations, which have great potential in antioxidant products.

Hepatocellular Carcinoma in Asia: Physician and Patient Perspectives on Surveillance, Diagnosis, and Treatment.

PURPOSE: In several Asian countries, hepatocellular carcinoma (HCC) is a leading cause of cancer deaths. HCC risk factors in Asia differ from those elsewhere and are changing with the treatment landscape as systemic treatment options increase. This study was conducted to gain insight from physicians and patients into HCC screening, diagnosis, and treatment strategies in Indonesia, Korea, Malaysia, Singapore, Taiwan, Thailand, and Vietnam. METHODS: Two cross-sectional, anonymized, online surveys were completed between July and December 2022 by physicians diagnosing and treating HCC (55 questions on risk factors, surveillance, diagnosis, and treatment) and patients ≥ 18 years old diagnosed with HCC (36 questions on disease knowledge, quality of life, and experiences of diagnosis and treatment). RESULTS: Responses were received from 276 physicians in all 7 countries and 130 patients in Thailand, Taiwan, and Vietnam. From the physician's perspective, surveillance programs are widespread but identify insufficient HCC cases; only 18% are early-stage HCC at diagnosis. From the patient's perspective, knowledge of risk factors increases after diagnosis, but few seek support from patient associations; patients would benefit from better communication from their doctors. Treatment affordability and side effects are key issues for patients. CONCLUSIONS: Awareness of the risk factors for HCC should be raised in primary care and the general population, and surveillance should identify early-stage HCC. Because patients rely on their doctors for support, doctors should better understand their patients' needs, and patients could be supported by trained nurses or case managers. Programs are needed to increase patients' access to proven HCC treatments.

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Correlation analysis between driver gene mutation and clinicopathological features in lung adenocarcinoma based on real-world cumulative clinical data.

Background: Driver genes are essential predictors of targeted therapeutic efficacy. Detecting driver gene mutations in lung adenocarcinoma (LUAD) patients can help to screen for targeted drugs and improve patient survival benefits. This study aims to investigate the mutation characterization of driver genes and their correlation with clinicopathological features in LUAD. Methods: A total of 440 LUAD patients were selected from Sir Run Run Shaw Hospital between July 2019 and September 2022. Postoperative tissue specimens were analyzed for gene mutations using next-generation sequencing technology, focusing, including epidermal growth factor receptor EGFR, ALK, ROS1, RET, KRAS, MET, BRAF, HER2, PIK3CA and NRAS. At the same time, clinicopathological data were collected and organized for multidimensional correlation analysis. Results: Of 440 LUAD patients, driver gene mutations were not detected in 48 patients. The proportion of patients with driver gene mutations was as high as 89.09%. The top three driver genetic mutations were EGFR, KRAS, and MET. Sixty-nine types of EGFR mutations were detected and distributed in the protein tyrosine kinase catalytic domain (56, 81.16%), Furin-like cysteine-rich region (9, 13.04%), receptor binding domain (3, 4.35%), and EGFR transmembrane domain (1, 1.45%). Single gene locus mutation occurred in 343 LUAD patients, but the mutation gene types covered all tested genes. Our findings showed that EGFR mutations were more commonly observed in non-smoking and female patients (P<0.01), KRAS mutations were more prevalent in male patients and smokers (P<0.01), ROS1 mutations had larger tumor diameters (P<0.01) and RET mutations were more prevalent in smokers (P<0.05). Conclusions: LUAD patients exhibit diverse genetic mutations, which may co-occur simultaneously. Integrated analysis of multiple mutations is essential for accurate diagnosis and effective treatment of the disease. The use of NGS can significantly expand our understanding of gene mutations and facilitate integrated analysis of multiple gene mutations, providing critical evidence for targeted treatment methods.