Analysis of volatile compound metabolic profiles during the fermentation of filler tobacco leaves through integrated E-nose, GC-MS, GC-IMS, and sensory evaluation.

Tobacco is an agricultural commodity with great economic significance. Producers recognize that the flavor characteristics of filler tobacco clear-out (FTLs) affect the quality of cigar tobacco items. To identify the major volatile organic compounds (VOCs) responsible for differences in FTLs, E-nose, HS-SPME-GC-MS, and HS-GC-IMS were employed for multi-dimensional analysis of nine groups of FTLs at various fermentation stages. The E-nose results indicated a progressive increase in nitrogen-oxygen compounds during fermentation. Coupled with these findings, HS-SPME-GC-MS identified 56 VOCs, and HS-GC-IMS revealed 55 VOCs in the FTLs. Principal component analysis (PCA) suggested that FTLs from various fermentation stages of the Yunxue No 39 tobacco plant exhibit significant differences. Partial least squares discriminant analysis (PLS-DA), along with the variable importance in projection (VIP) method for feature selection, pinpointed 12 VOCs as the essential unmistakable metabolites embroiled within the agrarian fermenting prepare of matured FTLs. During the fermentation process, these crucial metabolites are predominantly enriched in pathways including pyruvate metabolism, phenylalanine metabolism, as well as nicotinate and nicotinamide metabolism. The study provides insights into the differences and diversity of FTLs at agricultural fermentation stages. It offers valuable information for optimizing the quality of agricultural fermentation and guiding the directional fermentation of tobacco leaves.

Cross-omics strategies and personalised options for lung cancer immunotherapy.

Lung cancer is one of the most common malignant tumours worldwide and its high mortality rate makes it a leading cause of cancer-related deaths. To address this daunting challenge, we need a comprehensive understanding of the pathogenesis and progression of lung cancer in order to adopt more effective therapeutic strategies. In this regard, integrating multi-omics data of the lung provides a highly promising avenue. Multi-omics approaches such as genomics, transcriptomics, proteomics, and metabolomics have become key tools in the study of lung cancer. The application of these methods not only helps to resolve the immunotherapeutic mechanisms of lung cancer, but also provides a theoretical basis for the development of personalised treatment plans. By integrating multi-omics, we have gained a more comprehensive understanding of the process of lung cancer development and progression, and discovered potential immunotherapy targets. This review summarises the studies on multi-omics and immunology in lung cancer, and explores the application of these studies in early diagnosis, treatment selection and prognostic assessment of lung cancer, with the aim of providing more personalised and effective treatment options for lung cancer patients.

Left inferior phrenic arterial malformation mimicking gastric varices: A case report and review of literature.

BACKGROUND: Gastric submucosal arterial dilation resulting from splenic artery occlusion represents an exceedingly rare etiology of acute upper gastrointestinal bleeding (UGIB). Although endoscopy is a widely utilized diagnostic and therapeutic modality for gastrointestinal bleeding, it has limitations in detecting arterial abnormalities. CASE SUMMARY: This report presents a rare case of massive UGIB in a 57-year-old male with a tortuous left inferior phrenic artery accompanied by splenic artery occlusion. "Gastric varices" was identified during the patient's endoscopy one year before hemorrhage. Despite initial hemostasis by endoscopic clipping, the patient experienced massive rebleeding after one month, requiring intervention with transcatheter arterial embolization (TAE) to achieve hemostasis. CONCLUSION: This is the first case to report UGIB due to a tortuous left inferior phrenic artery. This case highlights the limitations of endoscopy in identifying arterial abnormalities and emphasizes the potential of TAE as a viable alternative for the management of arterial bleeding in the gastrointestinal tract.

Drug loaded marine polysaccharides-based hydrogel dressings for treating skin burns.

Marine polysaccharide-based biomaterials possess a range of excellent functions and properties, such as antiviral, antioxidant, immune regulation, and promoting cell migration, and are widely used in modern medicine. In this study, a marine polysaccharide-based composite hydrogel was synthesized using carboxymethyl chitosan and oxidized fucoidan as matrix, and loads therapeutic drugs for the treatment of burn wounds infected with bacteria. The composite hydrogels can slowly release drugs at the wound site, providing a long-lasting therapeutic effect including antibacterial, antioxidant, and analgesic, in this way to facilitate the restoring of infected burn wounds by inhibiting bacterial infections, promoting cell migration, facilitating collagen regeneration, and restoring the abnormal alteration of factors such as IL-1ß and CD86.

The Prognostic Utility of the Triceps Skinfold Thickness Albumin Index in Colorectal Cancer Patients with Cachexia.

PURPOSE: To develop a simple and convenient inflammation-nutrition-adiposity biomarker to complement the TNM staging system, further assess the prognosis of patients with colorectal cancer cachexia. METHODS: This study was a multi-centre cohort study. The triceps skinfold thickness-albumin index (TA) was calculated by combining the triceps skinfold thickness (TSF) and serum albumin levels. Kaplan-Meier analysis and Cox proportional risk regression models were used to assess the relationship between the TA and all-cause mortality. Internal validation was carried out. RESULTS: We included 1025 patients with colorectal cancer cachexia, 61.2% of whom were male, with a mean age of 58.91 (12.45) years. As the TA increased, overall mortality decreased in female patients (hazard ratio [HR], 0.95) but not in male patients (HR, 0.99). Multivariate Cox analysis showed that patients in the normal TA group had a significantly lower risk of death than those in the low TA group (HR, 0.53, 95% CI, 0.40-0.72). Patients with a normal TA had a lower risk of malnutrition, poor quality of life, and poor short-term prognosis than those with a low TA. CONCLUSIONS: TA index enables clinicians to assess the prognosis of patients as early as possible to improve the survival of patients with colorectal cancer cachexia.

Etamsylate-loaded hydrogel composed of carboxymethyl chitosan and oxidized tannic acid for improved wound healing.

Proper wound dressing is essential to facilitate skin wound healing, stop bleeding, and prevent infections. Herein, carboxymethyl chitosan (CMC) was crosslinked with oxidized tannic acid (OTA) to form an adhesive and self-healing OTA/CMC hydrogel, and etamsylate was loaded to enhance the hemostatic effect of the hydrogel dressing. The resultant OTA/CMC/E hydrogel exhibited a spectrum of noteworthy attributes including excellent cell compatibility, high antioxidant activity, effective anti-bacterium, and excellent hemorrhage control. Functionally, it mitigated intracellular ROS levels, hindered the proliferation of Staphylococcus aureus, while also significantly reducing hemostasis duration and total blood loss. In vivo full-thickness skin incision results showed that the OTA/CMC/E hydrogel could efficiently accelerate in vivo wound closure and healing, promising as an advanced wound healing material.

Efficacy of traditional Chinese medicines in the treatment of solar lentigo based on network pharmacology and experimental validation.

BACKGROUND AND AIMS: Solar lentigo is a prevalent skin condition that affects a significant number of individuals. Fortunately, certain traditional Chinese medicines and monomers (TCMM) have proven effective in addressing these concerns. In this study, we evaluated the efficacy and underlying mechanism of TCMM, a combination of TCM and monomers in repairing solar lentigo. METHODS: We detected and identified the main compounds of TCM using liquid chromatography-mass spectrometry (LC-MS) and through the approach of network pharmacology, we screened drug and disease targets, visualized networks with Cytoscape software, analyzed targets via Gene ontology and KEGG, clinically validated predictions. In a mouse model, UVB-induced pigmentation was assessed, and the effects of TCMM were evaluated. A clinical trial on 30 patients validated the depigmenting agent. RESULTS: Active ingredients such as MSH, Butylated hydroxytoluen, Valerophenone, and Geranylacetone aid pigmentation treatment. One hundred and forty-three crore targets impact PI3K-Akt, MAPK signaling pathway, ect. pathways. TCMM reduced UVB-induced pigmentation, water loss, epidermal thickness, and melanin. It inhibited TYR, MITF, AKT1, VEGFA, PTGS2, TNF-α, IL-6, IL-1ß. Clinical and microscopic analysis showed significant pigmentation reduction. CONCLUSIONS: The treatment of solar lentigo can benefit from the TCMM. By targeting multiple factors and pathways, this approach offers a comprehensive and effective treatment strategy.

HER2 expression in upper tract urothelial carcinoma and the relationship with clinicopathological characteristics-an analysis of 155 patients in Southwest China.

OBJECTIVE: We aimed to evaluate the expression of HER2 in patients with upper tract urothelial carcinoma (UTUC) in Southwest China by using a relatively large cohort, and to determine the relationship between HER2 expression and clinicopathological characters. MATERIALS AND METHODS: We retrospectively enrolled the clinical data of 155 UTUC patients who have undergone radical nephroureterectomy (RNU) from March 2019 to September 2022. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest (Scores of 0 or 1 + were considered as negative and 2 + or 3 + as positive). Tumor molecular phenotype was classified by the panel of CK20, CK5/6, and CD44. RESULTS: HER2 was overexpressed in 55 (35.5%) patients. It was associated with pathologic characteristics such as grade (p = 0.017), tumor molecular phenotype (p < 0.001) and Ki-67 expression (p = 0.017). On univariate and multivariable logistic regression analysis, HER2 overexpression remained associated with higher grade (HR, 10.6; 95% CI 1.0-112.6; p = 0.050) and luminal molecular phenotype (HR, 8.0; 95% CI 1,6-38.4; p = 0.010). During disease progression after nephroureterectomy, the phenotype of the tumor might change and a switch phenomenon in phenotype after recurrence in the bladder was reported. CONCLUSION: According to our study, in Southwest China, one-third of UTUC patients overexpressed HER2. Tumors with high grade or luminal phenotype tended to be HER2 positive. HER2 may represent a promising target for therapy in UTUC.

Association of MTHFR C677T, MTHFRA1298C, and MTRRA66G Gene Polymorphisms with Hyperhomocysteinemia and Its Modulation by the Combined Effect of Vitamin B12 and Folate in Chinese Population with Hypertension.

BACKGROUND: In China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear. OBJECTIVE: This study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension. METHODS: This study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry. RESULTS: Our findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 µmol/L vs. 11.15 µmol/L, P < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT). CONCLUSIONS: Adequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy. This trial was registered at clinicaltrials.gov as ChiCTR2100051983.

[Endoscopic assisted parathyroid surgery via a subclavian approach].

Objective:To explore the safety and efficacy of airless endoscopic surgery in the treatment of parathyroid diseases. Methods:By retrospective comparison, clinical treatment of 26 patients with primary hyperparathyroidism admitted to the Department of Otolaryngology and Head and Neck Surgery of the Hospital, Sun Yat-sen University from January 2018 to January 2023 were collected. They were divided into traditional group（13 cases） and endoscopic group（13 cases） according to the surgical method. The traditional group underwent traditional open parathyroid surgery, and the endoscopic group underwent airless endoscopic surgery through the subclavian approach. The efficacy, postoperative incision pain, incidence of adverse events, and aesthetic effects of the two groups were evaluated. Results:A total of 26 patients were included, including 13 patients in the traditional group and 13 patients in the endoscopic group. There was no significant difference in the incidence of hypocalcemia and transient hypoparathyroidism on the first day after surgery between the two groups（P>0.05）. No patients with incision pain（>3 points） or swallowing pain were found in both groups after the operation, and they were afraid or unwilling to cough and expel phlegm. There were no significant differences in the amount of blood loss, duration of operation, incidence of temporary recurrent laryngeal nerve palsy and transient hypocalcemia, and postoperative pain score between the two groups. The endoscopic group's scar evaluation score and aesthetic effect satisfaction score at 6 months after surgery were higher than those of the traditional group（P<0.01）. Conclusion:Airless Endoscopic parathyroid surgery via the subclavian approach has good effectiveness and safety, which did not significantly increase the risk of surgery. It can safely remove the lesion and leave no surgical scar on the anterior neck, which has the advantage of a good cosmetic effect. It is a safe and feasible endoscopic parathyroid surgery and can be used as a new choice for patients undergoing parathyroid surgery.

Network analysis retrieving bioactive compounds from Spirulina (Arthrospira platensis) and their targets related to systemic lupus erythematosus.

Immunosuppressive drugs are essential for systemic lupus erythematosus (SLE) treatment, but there are concerns about their toxicity. In this study, Arthrospira platensis was used as a resource for screening of the SLE-related bioactive compounds. To discover the potential compounds, a total of 833 compounds of A. platensis C1 were retrieved from the Spirulina-Proteome Repository (SpirPro) database and by literature mining. We retrieved structures and bioassays of these compounds from PubChem database; and collected approved and potential drugs for SLE treatment from DrugBank and other databases. The result demonstrated that cytidine, desthiobiotin, agmatine, and anthranilic acid, from the alga, has Tanimoto matching scores of 100% with the following drugs: ß-arabinosylcytosine/cytarabine, d-dethiobiotin, agmatine, and anthranilic acid, respectively. The bioassay matching and disease-gene-drug-compound network analysis, using VisANT 4.0 and Cytoscape, revealed 471 SLE-related genes. Among the SLE-related genes, MDM2, TP53, and JAK2 were identified as targets of cytarabine, while PPARG and IL1B were identified as targets of d-dethiobiotin. Binding affinity between the drug ligands and the algal bioactive compound ligands with their corresponding receptors were similarly comparable scores and stable, examined by molecular docking and molecular dynamic simulations, respectively.

Telemedicine-medical "snack community"-PHS ecosystem: Insights into the double-edged sword role of telemedicine in clinical practice and medical education during the COVID-19 pandemic and beyond.

Telemedicine has gained tremendous development during the COVID-19 pandemic. With deblocking and opening, telemedicine accelerates the evolvution of the medical "snack community" and undermines the perception of medical students and staff, which promotes the incidence of psychosocial-related disorders. Moreover, the inconsistent telemedicine adaptability between medical workers and patients aggravates the doctor-patient conflict due to the aging population and COVID-19 squeal. Telemedicine is colliding with the national healthcare system, whose synchronization with conventional medical service is crucial to coordinate the relationship among medical payment, patient privacy and qualifications of clinicians. This study puts more emphasis on the double-edged sword role of telemedicine in clinical practice and medical education during the COVID-19 pandemic and beyond. Overall, while telemedicine has demonstrated its utility in health care throughout the COVID pandemic, it is pretty critical to continue evaluating the efficacy and limitations of telemedicine in order to maintain equal access to medical service and high-quality medical education. A new concept as telemedicine-medical "snack community"-PHS ecosystem, where the psychological health education system and partners healthcare system with enough bandwidth, especially 5G technology, could optimize the effect of telemedicine on medical practice and education, is proposed.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

Investigation on environmental factors contributing to bispecific antibody stability and the reversal of self-associated aggregates.

Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors-such as pH, buffer types, ionic strength, protein concentrations, and temperatures-on its stability and the reversal of its self-associated aggregates. Mildly acidic, low-salt conditions were found optimal, ensuring bsAb stability for 30 days even at elevated temperature of 40 °C. Furthermore, these conditions facilitated the reversal of its self-associated aggregates to monomers during the initial 7-day incubation period. Our findings underscore the robustness and resilience of Fab-scFv format bsAb, further confirming its potential manufacturability despite its current absence as commercial products.

ARNTL2 facilitates bladder cancer progression through potentiating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner.

BACKGROUND: Basic helix-loop-helix ARNT like 2 (ARNTL2) is a transcription factor that controls the circadian rhythm. Amounts of studies have demonstrated the carcinogenic function of ARNTL2 in human malignant tumors albeit the underlying mechanisms remain poorly understood. We aimed to study the significance of ARNTL2 in bladder cancer (BLCA). METHODS: Immunohistochemical staining, immunoblotting and the database from TCGA were used to analyze the clinical relevance of ARNTL2, enolase 1 (ENO1) and solute carrier family 31 member 1 (SLC31A1) in BLCA. The function of ARNTL2 was explored by cell proliferation assay, apoptosis, colony formation and xenografted tumorigenesis. The molecular mechanisms of ARNTL2-driving BLCA development were investigated by RT-qPCR, immunoblotting and luciferase assays. Glycolysis was checked by measuring glucose consumption and lactate production. ENO1 activity was assessed by using indicated assay kit. RESULTS: Overexpression of ARNTL2 facilitates the proliferation and tumorigenesis of BLCA cells through suppression of apoptosis and enhancement of glycolysis. Up-regulation of SLC31A1, ENO1, and enhancement of SLC31A1-mediated ENO1 activity were critical for ARNTL2-triggered glycolysis and malignant growth in BLCA cells. ARNTL2 was positively correlated with SLC31A1 and ENO1 in BLCA patients. High expression of ARNTL2, SLC31A1 or ENO1 predicted the poor prognosis of BLCA patients. Depletion of SLC31A1 and inhibition of glycolysis completely blunted the growth ability of BLCA cells. CONCLUSION: In summary, ARNTL2 facilitates the progression of BLCA via activating ENO1-mediated glycolysis in a SLC31A1-independent and -dependent manner. Inhibiting SLC31A1 and glycolysis may be an aspirational approach for the treatment of BLCA patients with overexpression of ARNTL2.

IgG4-related disease with nasopharyngeal malignancy-like manifestations.

Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.

Semiconductor laser systems excited by multiplicative Ornstein-Uhlenbeck noise and additive sine-Wiener noise in relation to real and imaginary parts.

In this paper we study a semiconductor laser system excited by multiplicative Ornstein-Uhlenbeck (OU) noise and additive sine-Wiener (SW) noise with a related real part and imaginary part. The two-dimensional Langevin equation (LE) with cross-correlating complex OU noise and complex SW noise is equivalent to the six-dimensional LE. Based on functional methods and spatial dimension extension methods, the six-dimensional Fokker-Planck equation (FPE) is achieved. Through Taylor expansion approximation and linear transformation, the dimensionality of FPE is reduced, and the exact expression of the probability distribution (SPD) in steady state is obtained. The impacts of noise parameters on laser intensity on SPD are further analyzed. Moreover, based on the reduced FPE, the information entropy of the system is obtained. This calculation is useful for us to understand further the influence of system parameters and noise correlation coefficient on the system. The main work lies in obtaining an alternative method for deriving a FPE corresponding to the two-dimensional stochastic semiconductor laser model, which is more applicable than methods in previous literature. An equivalent expression for cross-correlated OU noise and cross-correlated SW noise as well as a method for approximate solutions of a high-dimensional FPE are also provided.

Preoperative blood-based nutritional biomarkers as significant prognostic factors after intravesical BCG therapy in patients with non-muscle-invasive bladder cancer.

The aim of this study was to investigate the prognostic role of blood-based nutritional biomarkers, including red blood cell (RBC count), hemoglobin (Hb), total protein (TP), albumin, the serum albumin to globulin ratio (AGR) and the prognostic nutritional index (PNI) in patients who underwent intravesical treatment for non-muscle invasive bladder cancer (NMIBC). A total of 501 NMIBC patients who received intravesical Bacillus Calmette-Guerin (BCG) treatment following transurethral resection of bladder tumor (TURBT) were included. The optimal cutoff values for these nutrition-based indicators were determined using receiver operating characteristic curve analysis. We observed a significantly higher recurrence-free survival (RFS) rate in patients with elevated levels of RBC count, Hb, TP, and albumin. Cox univariate and multivariate Cox regression analyses demonstrated that serum albumin (P = 0.002, HR = 0.51, 95%CI: 0.33-0.78), RBC count (P = 0.002, HR = 0.50, 95%CI: 0.32-0.77), TP (P = 0.028, HR = 0.62, 95%CI: 0.41-0.95), Hb (P = 0.004, HR = 0.53, 95%CI: 0.33-0.84), AGR (P = 0.003, HR = 0.46, 95%CI: 0.27-0.76) and PNI (P = 0.019, HR = 0.56, 95%CI: 0.35-0.91) were significant independent factors predicting RFS. These cost-effective and convenient blood-based nutritional biomarkers have the potential to serve as valuable prognostic indicators for predicting recurrence in NMIBC patients undergoing BCG-immunotherapy.

Inhibition of KIF20A enhances the immunotherapeutic effect of hepatocellular carcinoma by enhancing c-Myc ubiquitination.

Immune therapy has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients, yet its efficacy remains limited, underscoring the urgency to identify new therapeutic targets and biomarkers. Here, we investigated the pathological and physiological roles of KIF20A and assess its potential in enhancing HCC treatment efficacy when combined with PD-1 inhibitors. We initially assess KIF20A's oncogenic function using liver-specific KIF20A knockout (Kif20a CKO) mouse models and orthotopic xenografts. Subsequently, we establish a regulatory axis involving KIF20A, FBXW7, and c-Myc, validated through construction of c-Myc splicing mutants. Large-scale clinical immunohistochemistry (IHC) analyses confirm the pathological relevance of the KIF20A-FBXW7-c-Myc axis in HCC. We demonstrate that KIF20A overexpression correlates with poor prognosis in HCC by competitively inhibiting FBXW7-mediated degradation of c-Myc, thereby promoting glycolysis and enhancing tumor proliferation. Conversely, KIF20A downregulation suppresses these effects, impairing tumor growth through c-Myc downregulation. Notably, KIF20A inhibition attenuates c-Myc-induced MMR expression, associated with improved prognosis in HCC patients receiving PD-1 inhibitor therapy. Furthermore, in Kif20a CKO HCC mouse models, we observe synergistic effects between Kif20a knockout and anti-PD-1 antibodies, significantly enhancing immunotherapeutic efficacy against HCC. Our findings suggest that targeting the KIF20A-c-Myc axis could identify HCC patients likely to benefit from anti-PD-1 therapy. In conclusion, we propose that combining KIF20A inhibitors with anti-PD-1 treatment represents a promising therapeutic strategy for HCC, offering new avenues for clinical development and patient stratification.

Four years of climate warming reduced dark carbon fixation in coastal wetlands.

Dark carbon fixation (DCF), conducted mainly by chemoautotrophs, contributes greatly to primary production and the global carbon budget. Understanding the response of DCF process to climate warming in coastal wetlands is of great significance for model optimization and climate change prediction. Here, based on a 4-yr field warming experiment (average annual temperature increase of 1.5°C), DCF rates were observed to be significantly inhibited by warming in coastal wetlands (average annual DCF decline of 21.6%, and estimated annual loss of 0.08-1.5 Tg C yr-1 in global coastal marshes), thus causing a positive climate feedback. Under climate warming, chemoautotrophic microbial abundance and biodiversity, which were jointly affected by environmental changes such as soil organic carbon and water content, were recognized as significant drivers directly affecting DCF rates. Metagenomic analysis further revealed that climate warming may alter the pattern of DCF carbon sequestration pathways in coastal wetlands, increasing the relative importance of the 3-hydroxypropionate/4-hydroxybutyrate cycle, whereas the relative importance of the dominant chemoautotrophic carbon fixation pathways (Calvin-Benson-Bassham cycle and W-L pathway) may decrease due to warming stress. Collectively, our work uncovers the feedback mechanism of microbially mediated DCF to climate warming in coastal wetlands, and emphasizes a decrease in carbon sequestration through DCF activities in this globally important ecosystem under a warming climate.