Lactone-to-Lactam Editing Alters the Pharmacology of Bilobalide.

Precise transformations of natural products (NPs) can fine-tune their physicochemical properties while preserving inherently complex and evolutionarily optimized parent scaffolds. Here, we report an unprecedented lactone-to-lactam transformation on bilobalide, thus improving its stability and paving the way for biological exploration of previously inaccessible chemical space that is highly representative of the parent structure. This late-stage molecular editing of bilobalide enables facile access to a unique library of lactam analogues with altered pharmacology. Through phenotypic screening, we identify BB10 as a hit compound with unexpected inhibition of ferroptotic cell death. We further reveal that BB10 suppresses ferroptosis by restoring the expression of glutathione peroxidase 4 (GPX4) in brain cells. This study highlights that even subtle changes on NP scaffolds can confer new pharmacological properties, inspiring the exploration of simple yet critical transformations on complex NPs.

Genome-Wide Analysis of Fruit Color and Carotenoid Content in Capsicum Core Collection.

This study investigated carotenoid content and fruit color variation in 306 pepper accessions from diverse Capsicum species. Red-fruited accessions were predominant (245 accessions), followed by orange (35) and yellow (20). Carotenoid profiles varied significantly across accessions, with capsanthin showing the highest mean concentration (239.12 µg/g), followed by ß-cryptoxanthin (63.70 µg/g) and zeaxanthin (63.25 µg/g). Total carotenoid content ranged from 7.09 to 2566.67 µg/g, emphasizing the diversity within the dataset. Correlation analysis revealed complex relationships between carotenoids, with strong positive correlations observed between total carotenoids and capsanthin (r = 0.94 ***), ß-cryptoxanthin (r = 0.87 ***), and zeaxanthin (r = 0.84 ***). Principal component analysis (PCA) identified two distinct carotenoid groups, accounting for 67.6% of the total variance. A genome-wide association study (GWAS) identified 91 significant single nucleotide polymorphisms (SNPs) associated with fruit color (15 SNPs) and carotenoid content (76 SNPs). These SNPs were distributed across all chromosomes, with varying numbers on each. Among individual carotenoids, α-carotene was associated with 28 SNPs, while other carotenoids showed different numbers of associated SNPs. Candidate genes encoding diverse proteins were identified near significant SNPs, potentially contributing to fruit color variation and carotenoid accumulation. These included pentatricopeptide repeat-containing proteins, mitochondrial proton/calcium exchangers, E3 ubiquitin-protein ligase SINAT2, histone-lysine N-methyltransferase, sucrose synthase, and various enzymes involved in metabolic processes. Seven SNPs exhibited pleiotropic effects on multiple carotenoids, particularly ß-cryptoxanthin and capsanthin. The findings of this study provide insights into the genetic architecture of carotenoid biosynthesis and fruit color in peppers, offering valuable resources for targeted breeding programs aimed at enhancing the nutritional and sensory attributes of pepper varieties.

Lipid control and stroke risk in atrial fibrillation patients treated with direct oral anticoagulants and statins.

INTRODUCTION: The risk of ischemic stroke and intracerebral hemorrhage (ICH) with intensive lipid control by statins among patients with atrial fibrillation (AF) who require direct oral anticoagulants (DOAC) is unclear. We aimed to determine the risks of ischemic stroke and ICH in AF patients treated with DOAC and statins. PATIENTS AND METHODS: In a population-based retrospective cohort study, we identified AF patients concurrently on DOAC and statins from 2015 to 2021 in Hong Kong. Primary outcome was ischemic stroke. Secondary outcomes were ICH and death. We correlated study outcomes with low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) as time-varying, continuous variables with restricted cubic spline. In secondary analyses, the risks of study outcomes with statin intensity (low, moderate, high) were determined by multivariable time-dependent marginal structural Cox models. RESULTS: We identified 32,752 AF patients co-prescribed with DOAC and statins. Lower LDL-C (p < 0.001) and higher HDL-C (p < 0.001) levels were associated with lower risk of ischemic stroke but not significantly associated with ICH. LDL-C of <1.8 mmol/L (70 mg/dL) was not associated with mortality (19.6% vs 18.4%, difference 1.2% [95% CI -0.35 to 2.13]). High-intensity statin was associated with a lower risk of ischemic stroke compared with low-intensity statin (weighted Cox-specific hazard ratio [95% CI]: 0.82 [0.67-0.99], p = 0.040) independent of LDL-C levels. Similar associations were found in 11,444 AF patients with a history of ischemic stroke. DISCUSSION AND CONCLUSION: Intensive lipid control by high-intensity statins was associated with a lower risk of ischemic stroke in AF patients who required DOACs and did not appear to increase the risk of ICH.

Value proposition of retinal imaging in Alzheimer's disease screening: A review of eight evolving trends.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Current diagnostic modalities of AD generally focus on detecting the presence of amyloid ß and tau protein in the brain (for example, positron emission tomography [PET] and cerebrospinal fluid testing), but these are limited by their high cost, invasiveness, and lack of expertise. Retinal imaging exhibits potential in AD screening and risk stratification, as the retina provides a platform for the optical visualization of the central nervous system in vivo, with vascular and neuronal changes that mirror brain pathology. Given the paradigm shift brought by advances in artificial intelligence and the emergence of disease-modifying therapies, this article aims to summarize and review the current literature to highlight 8 trends in an evolving landscape regarding the role and potential value of retinal imaging in AD screening.

APOE2 protects against Aß pathology by improving neuronal mitochondrial function through ERRα signaling.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease and apolipoprotein E (APOE) genotypes (APOE2, APOE3, and APOE4) show different AD susceptibility. Previous studies indicated that individuals carrying the APOE2 allele reduce the risk of developing AD, which may be attributed to the potential neuroprotective role of APOE2. However, the mechanisms underlying the protective effects of APOE2 is still unclear. METHODS: We analyzed single-nucleus RNA sequencing and bulk RNA sequencing data of APOE2 and APOE3 carriers from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort. We validated the findings in SH-SY5Y cells and AD model mice by evaluating mitochondrial functions and cognitive behaviors respectively. RESULTS: The pathway analysis of six major cell types revealed a strong association between APOE2 and cellular stress and energy metabolism, particularly in excitatory and inhibitory neurons, which was found to be more pronounced in the presence of beta-amyloid (Aß). Moreover, APOE2 overexpression alleviates Aß1-42-induced mitochondrial dysfunction and reduces the generation of reactive oxygen species in SH-SY5Y cells. These protective effects may be due to ApoE2 interacting with estrogen-related receptor alpha (ERRα). ERRα overexpression by plasmids or activation by agonist was also found to show similar mitochondrial protective effects in Aß1-42-stimulated SH-SY5Y cells. Additionally, ERRα agonist treatment improve the cognitive performance of Aß injected mice in both Y maze and novel object recognition tests. ERRα agonist treatment increased PSD95 expression in the cortex of agonist-treated-AD mice. CONCLUSIONS: APOE2 appears to enhance neural mitochondrial function via the activation of ERRα signaling, which may be the protective effect of APOE2 to treat AD.

Exploring Disease Resistance in Pepper (Capsicum spp.) Germplasm Collection Using Fluidigm SNP Genotyping.

This study utilized a diverse Capsicum accessions (5658) sourced from various species and geographical regions, deposited at the National Agrobiodiversity Center, Genebank. We employed 19 SNP markers through a Fluidigm genotyping system and screened these accessions against eight prevalent diseases of pepper. This study revealed accessions resistant to individual diseases as well as those exhibiting resistance to multiple diseases, including bacterial spot, anthracnose, powdery mildew, phytophthora root rot, and potyvirus. The C. chacoense accessions were identified as resistant materials against bacterial spot, anthracnose, powdery mildew, and phytophthora root rot, underscoring the robust natural defense mechanisms inherent in the wild Capsicum species and its potential uses as sources of resistance for breeding. C. baccatum species also demonstrated to be a promising source of resistance to major pepper diseases. Generally, disease-resistant germplasm has been identified from various Capsicum species. Originating from diverse locations such as Argentina, Bolivia, and the United Kingdom, these accessions consistently demonstrated resistance, indicating the widespread prevalence of disease-resistant traits across varied environments. Additionally, we selected ten pepper accessions based on their resistance to multiple diseases, including CMV, Phytophthora root rot, potyviruses, and TSWV, sourced from diverse geographical regions like Hungary, Peru, the United States, and the Netherlands. This comprehensive analysis provides valuable insights into disease resistance in Capsicum, crucial for fostering sustainable agricultural practices and advancing crop improvement through breeding strategies.

The Factors Influencing Chronic Kidney Disease Incidence: Database from the Korean National Health Insurance Sharing Service (NHISS).

Background: The global prevalence of chronic kidney disease (CKD) is increasing, with diabetes accounting for the highest proportion. We analyzed the influence of clinical factors on the incidence of CKD according to the renal function, primary focusing on patients with diabetes. Methods: We used the Sample Cohorts Database provided by the National Health Insurance Sharing Service (NHISS) in Korea. Participants aged ≥ 40 years who underwent a health checkup in 2009 were categorized into six groups based on their eGFR values (<60 mL/min, 60-89 mL/min, ≥90 mL/min) and the presence of diabetes. And all patients with CKD at 2009 screening were excluded. The participants were tracked from 2010 to 31 December 2019. The CKD incidence rate according to the eGFR values and the effect of the accompanying factors on CKD incidence were confirmed. Results: 148,089 people without CKD were analyzed. The CKD incidence rate was highest in those with eGFR < 60 mL/min with diabetes and lowest in those with eGFR ≥ 90 mL/min without diabetes. The CKD incidence rates were similar between the eGFR < 60 mL/min group without diabetes and the eGFR 60-89 mL/min group with diabetes. Compared to under 44 years of age, the hazard ratio of CKD incidence was 8 times higher in over 75 years of age. Men had a 1.7-fold higher risk of developing CKD than women. Current smoker, hypertension, dyslipidemia, myocardial infarction history, and atrial fibrillation and flutter increased the risk of CKD incidence. Age, diabetes, and baseline eGFR are important factors in the occurrence of CKD. As age increases, the risk of developing CKD in men increases compared to women. Conclusions: These results will be helpful in predicting risk groups for CKD and establishing strategies to lowering CKD incidence.

Cytosolic DNA sensors in neurodegenerative diseases: from physiological defenders to pathological culprits.

Cytosolic DNA sensors are a group of pattern recognition receptors (PRRs) that vary in structures, molecular mechanisms, and origins but share a common function to detect intracellular microbial DNA and trigger the innate immune response like type 1 interferon production and autophagy. Cytosolic DNA sensors have been proven as indispensable defenders against the invasion of many pathogens; however, growing evidence shows that self-DNA misplacement to cytoplasm also frequently occurs in non-infectious circumstances. Accumulation of cytosolic DNA causes improper activation of cytosolic DNA sensors and triggers an abnormal autoimmune response, that significantly promotes pathological progression. Neurodegenerative diseases are a group of neurological disorders characterized by neuron loss and still lack effective treatments due to a limited understanding of pathogenesis. But current research has found a solid relationship between neurodegenerative diseases and cytosolic DNA sensing pathways. This review summarizes profiles of several major cytosolic DNA sensors and their common adaptor protein STING. It also discusses both the beneficial and detrimental roles of cytosolic DNA sensors in the genesis and progression of neurodegenerative diseases.

Tracking and navigation of a microswarm under laser speckle contrast imaging for targeted delivery.

Micro/nanorobotic swarms consisting of numerous tiny building blocks show great potential in biomedical applications because of their collective active delivery ability, enhanced imaging contrast, and environment-adaptive capability. However, in vivo real-time imaging and tracking of micro/nanorobotic swarms remain a challenge, considering the limited imaging size and spatial-temporal resolution of current imaging modalities. Here, we propose a strategy that enables real-time tracking and navigation of a microswarm in stagnant and flowing blood environments by using laser speckle contrast imaging (LSCI), featuring full-field imaging, high temporal-spatial resolution, and noninvasiveness. The change in dynamic convection induced by the microswarm can be quantitatively investigated by analyzing the perfusion unit (PU) distribution, offering an alternative approach to investigate the swarm behavior and its interaction with various blood environments. Both the microswarm and surrounding environment were monitored and imaged by LSCI in real time, and the images were further analyzed for simultaneous swarm tracking and navigation in the complex vascular system. Moreover, our strategy realized real-time tracking and delivery of a microswarm in vivo, showing promising potential for LSCI-guided active delivery of microswarm in the vascular system.

Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants.

Importance: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear. Objective: To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management. Design, Setting, and Participants: In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023. Main Outcomes and Measures: The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified. Results: A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion. Conclusions and Relevance: In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.

Gastrointestinal Bleeding in Extracorporeal Membrane Oxygenation Patients: A Comprehensive Analysis of Risk Factors and Clinical Outcomes.

Background: Extracorporeal membrane oxygenation (ECMO) is an intervention for severe heart and lung failure; however, it poses the risk of complications, including gastrointestinal bleeding (GIB). Comprehensive analyses of GIB in patients undergoing ECMO are limited, and its impact on clinical outcomes remains unclear. Methods: This retrospective study included 484 patients who received venovenous and venoarterial ECMO between January 2015 and December 2022. Data collected included patient characteristics, laboratory results, GIB details, and interventions. Statistical analyses were performed to identify risk factors and assess the outcomes. Results: GIB occurred in 44 of 484 patients (9.1%) who received ECMO. Multivariable analysis revealed that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06; p=0.0130) and need to change the ECMO mode (OR, 3.74; 95% CI, 1.75-7.96; p=0.0006) were significant risk factors for GIB, whereas no association was found with antiplatelet or systemic anticoagulation therapies during ECMO management. Half of the patients with GIB (22/44, 50%) underwent intervention, with endoscopy as the primary modality (19/22, 86.4%). Patients who underwent ECMO and developed GIB had higher rates of mortality (40/44 [90.9%] vs. 262/440 [59.5%]) and ECMO weaning failure (38/44 [86.4%] vs. 208/440 [47.3%]). Conclusion: GIB in patients undergoing ECMO is associated with adverse outcomes, including increased risks of mortality and weaning failure. Even in seemingly uncomplicated cases, it is crucial to avoid underestimating the significance of GIB.

tPA-anchored nanorobots for in vivo arterial recanalization at submillimeter-scale segments.

Micro/nanorobots provide a promising approach for intravascular therapy with high precision. However, blood vessel is a highly complex system, and performing interventional therapy in those submillimeter segments remains challenging. While micro/nanorobots can enter submillimeter segments, they may still comprise nonbiodegradable parts, posing a considerable challenge for post-use removal. Here, we developed a retrievable magnetic colloidal microswarm, composed of tPA-anchored Fe3O4@mSiO2 nanorobots (tPA-nbots), to archive tPA-mediated thrombolysis under balloon catheter-assisted magnetic actuation with x-ray fluoroscopy imaging system (CMAFIS). By deploying tPA-nbot transcatheter to the vicinity of the thrombus, the tPA-nbot microswarms were magnetically actuated to the blood clot at the submillimeter vessels with high precision. After thrombolysis, the tPA-nbots can be retrieved via the CMAFIS, as demonstrated in ex vivo organ of human placenta and in vivo carotid artery of rabbit. The proposed colloidal microswarm provides a promising robotic tool with high spatial precision for enhanced thrombolysis with low side effects.

Shift in Tissue-Specific Immune Niches and CD137 Expression in Tuberculoma of Pembrolizumab-Treated Nasopharyngeal Carcinoma Patients.

The use of immune checkpoint inhibitors (ICIs) in cancer treatment has shown promise but can also have unintended consequences, such as reactivating latent tuberculosis (TB). To develop treatments that address ICIs-related adverse events, it is essential to understand cellular heterogeneity across healthy and pathological tissues. We performed cross-tissue multiplexed staining analysis on samples from two patients with TB reactivation during pembrolizumab treatment for metastatic nasopharyngeal carcinoma. CD8+ T cells, rather than CD4+ T cells, accumulated preferentially in the tuberculoma and were associated with increased production of IFNγ and expression of CD137. Additionally, CD137 enrichment played a role in the spatial organization of the tuberculoma, with specific interaction limited to spatial proximal cells between IFNγ+ CD137+ CD8+ T cells and IL12+ CD137+ type-1 macrophages. This unique feature was not observed in non-tumoral or tumoral tissues. Our analysis of public transcriptomic datasets supported the notion that this cellular interaction was more prominent in patients with durable ICI responses compared to those with non-ICI-related TB. We suggest that shifts towards CD137-rich immune niches are correlated with both off-target immune-related adverse events and anti-tumor efficacy. Targeting the tumor microenvironment through conditional activation of anti-CD137 signaling in combination with ICIs can modulate the reactivity of T cells and macrophages for localized tumor killing without the potential off-target immune-related risks associated with ICIs alone.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19: A Single-Center Study.

Background: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory failure, which frequently necessitates invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, the limited availability of ECMO resources poses challenges to patient selection and associated decision-making. Consequently, this retrospective single-center study was undertaken to evaluate the characteristics and clinical outcomes of patients with COVID-19 receiving ECMO. Methods: Between March 2020 and July 2022, 65 patients with COVID-19 were treated with ECMO and were subsequently reviewed. Patient demographics, laboratory data, and clinical outcomes were examined, and statistical analyses were performed to identify risk factors associated with mortality. Results: Of the patients studied, 15 (23.1%) survived and were discharged from the hospital, while 50 (76.9%) died during their hospitalization. The survival group had a significantly lower median age, at 52 years (interquartile range [IQR], 47.5-61.5 years), compared to 64 years (IQR, 60.0-68.0 years) among mortality group (p=0.016). However, no significant differences were observed in other underlying conditions or in factors related to intervention timing. Multivariable analysis revealed that the requirement of a change in ECMO mode (odds ratio [OR], 366.77; 95% confidence interval [CI], 1.92-69911.92; p=0.0275) and the initiation of continuous renal replacement therapy (CRRT) (OR, 139.15; 95% CI, 1.95-9,910.14; p=0.0233) were independent predictors of mortality. Conclusion: Changes in ECMO mode and the initiation of CRRT during management were associated with mortality in patients with COVID-19 who were supported by ECMO. Patients exhibiting these factors require careful monitoring due to the potential for adverse outcomes.

High-resolution omics of vascular ageing and inflammatory pathways in neurodegeneration.

High-resolution omics, particularly single-cell and spatial transcriptomic profiling, are rapidly enhancing our comprehension of the normal molecular diversity of gliovascular cells, as well as their age-related changes that contribute to neurodegeneration. With more omic profiling studies being conducted, it is becoming increasingly essential to synthesise valuable information from the rapidly accumulating findings. In this review, we present an overview of the molecular features of neurovascular and glial cells that have been recently discovered through omic profiling, with a focus on those that have potentially significant functional implications and/or show cross-species differences between human and mouse, and that are linked to vascular deficits and inflammatory pathways in ageing and neurodegenerative disorders. Additionally, we highlight the translational applications of omic profiling, and discuss omic-based strategies to accelerate biomarker discovery and facilitate disease course-modifying therapeutics development for neurodegenerative conditions.

Sequential treatment in advanced epidermal growth factor receptor-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with 1st/2nd-generation EGFR-tyrosine kinase inhibitors.

Introduction: The clinical outcomes of sequential treatment of advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs are unclear. Thus, we aimed to analyze the outcomes of these patients. Methods: Between January 2015 and December 2020, data for 102 advanced EGFR-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with erlotinib or afatinib followed by treatments at multiple institutions were retrospectively analyzed. All patients with progressive disease (PD) after first-line therapy underwent secondary T790M mutation detection. Results: The secondary T790M mutation positive rate of all study patients was 57.9%. First-line erlotinib use and progression-free survival (PFS) after first-line therapy > 12 months were positively associated with the T790M mutation (P <0.05). The response rates (RRs) to second-line treatments were 51.7% and 22.7% for the osimertinib and nonosimertinib groups, respectively (P = 0.001). The median PFS associated with second-line osimertinib and nonosimertinib therapy was 13.7 and 7.1 months, respectively (hazard ratio (HR) = 0.38; 95% confidence interval (CI), 0.23-0.63; P< 0.001). Patients with a secondary T790M mutation receiving second-line osimertinib treatment had a median overall survival (OS) of 54.3 months, and the median OS was 31.9 months for non-T790M-mutated patients receiving second-line nonosimertinib treatments (HR = 0.36; CI: 0.21-0.62, P < 0.001). Conclusion: The majority of acquired resistance to first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs is associated with the T790M mutation. Sequential osimertinib treatment in patients with positive secondary T790M mutation is associated with better outcomes among these patients.

Clinical outcome analysis of non-small cell lung cancer patients with brain metastasis receiving metastatic brain tumor resection surgery: a multicenter observational study.

Brain metastasis is most common in primary non-small cell lung cancer (NSCLC), and some patients require neurosurgical resection for intracranial disease control. Because advances in systemic therapies for metastatic NSCLC have been developed in the past decade, we aimed to analyze and determine clinical factors associated with the postresection survival of NSCLC patients with brain metastasis who underwent neurosurgery followed by systemic therapy. Between January 2017 and December 2021, data for 93 NSCLC patients with brain metastasis treated with neurosurgery followed by systemic therapy at Linkou, Kaohsiung and Chiayi Chang Gung Memorial Hospitals were retrospectively retrieved for analysis. For all study patients, median postresection survival was 34.36 months (95% confidence interval (CI), 28.97-39.76), median brain metastasis (BM)-free survival was 26.90 months (95% CI, 22.71-31.09), and overall survival (OS) was 41.13 months (95% CI, 34.47-47.52). In multivariate analysis, poor performance status (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2) and concurrent liver metastasis were identified as independent unfavorable factors associated with significantly shortened postresection survival (P<0.001). The histological type adenocarcinoma was associated with significantly longer postresection survival (P = 0.001). The median postresection survival for adenocarcinoma and nonadenocarcinoma patients was 36.23 and 10.30 months, respectively (hazard ratio (HR) = 0.122; 95% CI, 0.035-0.418; P<0.001); that for patients with and without concurrent liver metastasis was 11.43 and 36.23 months, respectively (HR = 22.18; 95% CI, 5.827-84.459; P<0.001). Patients with preserved ECOG PS, adenocarcinoma histology type and no concurrent liver metastasis appeared to have better postresection survival than nonadenocarcinoma patients. Our results provide counseling and decision-making references for neurosurgery feasibility in NSCLC patients with brain metastasis.

A Comprehensive Genome-Wide Association Study of Carotenoid and Capsaicinoid Contents in Capsicum chinense Germplasm.

Pepper is a highly important vegetable globally, both economically and nutritionally. However, to efficiently select and identify genetic resources for pepper breeding programs, it is crucial to understand the association between important traits and genetic factors. In this study, we investigated the genetic basis of carotenoid and capsaicinoid content in 160 Capsicum chinense germplasms. The study observed significant variability in carotenoid and capsaicinoid content among the germplasms. Correlation analysis revealed a strong positive correlation between violaxanthin and antheraxanthin. In contrast, capsaicin and dihydrocapsaicin displayed negative correlations with individual carotenoids but exhibited a strong positive correlation between the two compounds (r = 0.90 ***). Genotyping-by-sequencing (GBS) was performed on 160 genotypes of pepper germplasm, which identified 47,810 high-quality SNPs. A comprehensive genome-wide association analysis was performed using these SNPs to identify SNPs associated with carotenoids and capsaicinoids, revealing 193 SNPs that exhibited significant associations. Specifically, 4 SNPs were associated with violaxanthin, 2 with antheraxanthin, 86 with capsorubin, 5 with capsanthin, 63 with zeaxanthin, 3 with ß-cryptoxanthin, and 2 with α-carotene. With further studies, the significantly associated SNPs identified in this study have the potential to be utilized for selecting pepper accessions with high carotenoid and capsaicinoid contents. Additionally, the genes associated with these significant SNPs will be used to understand their roles and involvement in the biosynthesis pathway of carotenoids and capsaicinoids. Understanding the function of these genes can provide insights into the molecular mechanisms underlying the production of these bioactive compounds in pepper. The findings of this study hold valuable implications for selecting pepper varieties with desirable traits and developing breeding programs aimed at enhancing the nutritional and medicinal properties of pepper.