Electrochemically coupled CH4 and CO2 consumption driven by microbial processes.

The chemical transformations of methane (CH4) and carbon dioxide (CO2) greenhouse gases typically have high energy barriers. Here we present an approach of strategic coupling of CH4 oxidation and CO2 reduction in a switched microbial process governed by redox cycling of iron minerals under temperate conditions. The presence of iron minerals leads to an obvious enhancement of carbon fixation, with the minerals acting as the electron acceptor for CH4 oxidation and the electron donor for CO2 reduction, facilitated by changes in the mineral structure. The electron flow between the two functionally active microbial consortia is tracked through electrochemistry, and the energy metabolism in these consortia is predicted at the genetic level. This study offers a promising strategy for the removal of CH4 and CO2 in the natural environment and proposes an engineering technique for the utilization of major greenhouse gases.

Embracing ChatGPT for Medical Education: Exploring Its Impact on Doctors and Medical Students.

ChatGPT (OpenAI), a cutting-edge natural language processing model, holds immense promise for revolutionizing medical education. With its remarkable performance in language-related tasks, ChatGPT offers personalized and efficient learning experiences for medical students and doctors. Through training, it enhances clinical reasoning and decision-making skills, leading to improved case analysis and diagnosis. The model facilitates simulated dialogues, intelligent tutoring, and automated question-answering, enabling the practical application of medical knowledge. However, integrating ChatGPT into medical education raises ethical and legal concerns. Safeguarding patient data and adhering to data protection regulations are critical. Transparent communication with students, physicians, and patients is essential to ensure their understanding of the technology's purpose and implications, as well as the potential risks and benefits. Maintaining a balance between personalized learning and face-to-face interactions is crucial to avoid hindering critical thinking and communication skills. Despite challenges, ChatGPT offers transformative opportunities. Integrating it with problem-based learning, team-based learning, and case-based learning methodologies can further enhance medical education. With proper regulation and supervision, ChatGPT can contribute to a well-rounded learning environment, nurturing skilled and knowledgeable medical professionals ready to tackle health care challenges. By emphasizing ethical considerations and human-centric approaches, ChatGPT's potential can be fully harnessed in medical education, benefiting both students and patients alike.

Blood cell parameters and risk of nonalcoholic fatty liver disease: a comprehensive Mendelian randomization study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR). METHODS: We analyzed data from 4,198 participants in the 2017-2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD. RESULTS: Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method. CONCLUSIONS: Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.

Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.

Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from  laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

Comprehensive prognostic and immune analysis of sterol O-acyltransferase 1 in patients with hepatocellular carcinoma.

BACKGROUND: Sterol O-acyltransferase 1 (SOAT1) is an important target in the diagnosis and treatment of liver cancer. However, the prognostic value of SOAT1 in patients with hepatocellular carcinoma (HCC) is still not clear. AIM: To investigate the correlation of SOAT1 expression with HCC, using RNA-seq and gene expression data of The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) and pan-cancer. METHODS: The correlation between SOAT1 expression and HCC was analyzed. Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC. Overall survival and disease-specific survival were explored based on TCGA-LIHC data. Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. In addition, the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy. RESULTS: SOAT1 and SOAT2 were highly expressed in unpaired samples, while only SOAT1 was highly expressed in paired samples. The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748, while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676. Patients with higher SOAT1 expression had lower survival rates. Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway, the IL-18 signaling pathway, the calcium signaling pathway, secreted factors, the Wnt signaling pathway, the Jak/STAT signaling pathway, the MAPK family signaling pathway, and cell-cell communication were involved in such association. SOAT1 expression was positively associated with the abundance of macrophages, Th2 cells, T helper cells, CD56bright natural killer cells, and Th1 cells, and negatively linked to the abundance of Th17 cells, dendritic cells, and cytotoxic cells. CONCLUSION: Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment, which is helpful for the development of new strategies for immunotherapy and metabolic therapy.

Second Primary Breast Cancer in Young Breast Cancer Survivors.

Importance: Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC. Objective: To estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC. Design, Setting, and Participants: Participants were enrolled in the Young Women's Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. Main Outcomes and Measures: The 5- and 10- year cumulative incidence of SPBC. Results: In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70). Conclusions: Findings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.

IL6/adiponectin/HMGB1 feedback loop mediates adipocyte and macrophage crosstalk and M2 polarization after myocardial infarction.

Background: Differences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone. Methods: The LVA, MI, and SHAM mouse models were used. Echocardiography, Masson's trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN. Results: A novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment. Conclusion: The IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.

Effect of Cymbopogon martini (Roxb.) Will.Watson essential oil on antioxidant activity, immune and intestinal barrier-related function, and gut microbiota in pigeons infected by Candida albicans.

Essential oils are potential alternatives to antibiotics for preventing Candida albicans (C. albicans) infection which is responsible for economic losses in the pigeon industry. Cymbopogon martini essential oil (EO) can inhibit pathogens, particularly fungal pathogens but its potential beneficial effects on C. albicans-infected pigeons remain unclear. Therefore, we investigated the impact of C. martini EO on antioxidant activity, immune response, intestinal barrier function, and intestinal microbiota in C. albicans-infected pigeons. The pigeons were divided into four groups as follows: (1) NC group: C. albicans uninfected/C. martini EO untreated group; (2) PC group: C. albicans infected/C. martini EO untreated group; (3) LPA group: C. albicans infected/1% C. martini EO treated group; and (4) HPA group: C. albicans infected/2% C. martini EO treated group. The pigeons were infected with C. albicans from day of age 35 to 41 and treated with C. martini EO from day of age 42 to 44, with samples collected on day of age 45 for analysis. The results demonstrated that C. martini EO prevented the reduction in the antioxidant enzymes SOD and GSH-Px causes by C. albicans challenge in pigeons. Furthermore, C. martini EO could decrease the relative expression of IL-1ß, TGF-ß, and IL-8 in the ileum, as well as IL-1ß and IL-8 in the crop, while increasing the relative expression of Claudin-1 in the ileum and the crop and Occludin in the ileum in infected pigeons. Although the gut microbiota composition was not significantly affected by C. martini EO, 2% C. martini EO increased the abundance of Alistipes and Pedobacter. In conclusion, the application of 2% C. martini EO not only enhanced the level of antioxidant activity and the expression of genes related to intestinal barrier function but also inhibited inflammatory genes in C. albicans-infected pigeons and increased the abundance of gut bacteria that are resistant to C. albicans.

Tumor-suppressive miR-4732-3p is sorted into fucosylated exosome by hnRNPK to avoid the inhibition of lung cancer progression.

BACKGROUND: Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. METHODS: A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. RESULTS: We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. CONCLUSIONS: NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.

2% supramolecular salicylic acid hydrogel vs. adapaline gel in mild to moderate acne vulgaris treatment: A multicenter, randomized, evaluator-blind, parallel-controlled trial.

OBJECTIVE: Salicylic acid (SA) has been used for treatment of acne of different severity levels. However, there are few researches about the safety and efficacy for treatment of mild to moderate acne, and the improvement of the skin condition by using 2% supramolecular salicylic acid (SSA) compared to Davuwen Adapaline gel. METHODS: A multicenter, randomized, assessor-blind and parallel-controlled study was conducted. A total of 500 patients (trial group: 249, control group: 251) with mild to moderate (grade I-II) facial acne vulgaris were recruited in this study over a 16-week trial period. Patients in the trial group were treated with Broda 2% SSA hydrogel, while control group treated with Davuwen Adapaline gel once a day. The number of inflammatory papules, comedones, and pustules were counted and the rate of lesion reduction was calculated pre- and post-treatment. Then, the skin physiological indicators, including L*a*b*, TEWL, skin sebum and hydration were measured. Statistical analysis was conducted using SAS 9.4. Significance was set at p = 0.05. RESULTS: At the end of 12 weeks' therapy, the regression and markedly improvement rate of the trail group and the control group were 51.01% and 43.10% respectively, and there was no significant difference in the improvement rate between two groups (p = 0.0831). Although, there was no difference in adverse events rate between two groups, the adverse events rate of the trail group was 0.40%, a little lower than the control group (0.80%). Moreover, there was a significant difference in the numbers of pores at T1 between two groups. CONCLUSION: Both 2% SSA and Adapaline gel were equally effective in the treatment of mild to moderate acne vulgaris. 2% SSA is worth the clinical promotion and application in mild to moderate acne vulgaris.

Attributable mortality of acute kidney injury among critically ill patients with sepsis: a multicenter, retrospective cohort study.

BACKGROUND: Sepsis and acute kidney injury (AKI) are common severe diseases in the intensive care unit (ICU). This study aimed to estimate the attributable mortality of AKI among critically ill patients with sepsis and to assess whether AKI was an independent risk factor for 30-day mortality. METHODS: The information we used was derived from a multicenter prospective cohort study conducted in 18 Chinese ICUs, focusing on septic patients post ICU admission. The patients were categorized into two groups: those who developed AKI (AKI group) within seven days following a sepsis diagnosis and those who did not develop AKI (non-AKI group). Using propensity score matching (PSM), patients were matched 1:1 as AKI and non-AKI groups. We then calculated the mortality rate attributable to AKI in septic patients. Furthermore, a survival analysis was conducted comparing the matched AKI and non-AKI septic patients. The primary outcome of interest was the 30-day mortality rate following the diagnosis of sepsis. RESULTS: Out of the 2175 eligible septic patients, 61.7% developed AKI. After the application of PSM, a total of 784 septic patients who developed AKI were matched in a 1:1 ratio with 784 septic patients who did not develop AKI. The overall 30-day attributable mortality of AKI was 6.6% (95% CI 2.3 ∼ 10.9%, p = 0.002). A subgroup analysis revealed that the 30-day attributable mortality rates for stage 1, stage 2, and stage 3 AKI were 0.6% (95% CI -5.9 ∼ 7.2%, p = 0.846), 4.7% (95% CI -3.1 ∼ 12.4%, p = 0.221) and 16.8% (95% CI 8.1 ∼ 25.2%, p < 0.001), respectively. Particularly noteworthy was that stage 3 AKI emerged as an independent risk factor for 30-day mortality, possessing an adjusted hazard ratio of 1.80 (95% CI 1.31 ∼ 2.47, p < 0.001). CONCLUSIONS: The overall 30-day attributable mortality of AKI among critically ill patients with sepsis was 6.6%. Stage 3 AKI had the most significant contribution to 30-day mortality, while stage 1 and stage 2 AKI did not increase excess mortality.

Attributable mortality of ARDS among critically ill patients with sepsis: a multicenter, retrospective cohort study.

BACKGROUND: Both sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis. METHODS: The data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis. RESULTS: 2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS's overall 30-day attributable mortality was 11.9% (95% CI 7.5-16.3%, p < 0.001). Subgroup analysis showed that the 30-day attributable mortality of mild, moderate, and severe ARDS was 10.5% (95% CI 4.0-16.8%, p < 0.001), 11.6% (95% CI 4.7-18.4%, p < 0.001) and 18.1% (95% CI 4.5-30.9%, p = 0.006), respectively. ARDS was an independent risk factor for 30-day mortality, with adjusted hazard ratios of 1.30 (95% CI 1.03-1.64, p = 0.027), 1.49 (95% CI 1.20-1.85, p < 0.001), and 1.95 (95% CI 1.51-2.52, p < 0.001) for mild, moderate, and severe ARDS, respectively. CONCLUSIONS: The overall 30-day attributable mortality of ARDS among critically ill patients with sepsis was 11.9%. Compared with mild and moderate ARDS, severe ARDS contributed more to death. ARDS was significantly associated with an increase in the 30-day mortality.

Histone methyltransferase SETD2 is required for proper hippocampal lamination and neuronal maturation.

Proper formation of the hippocampus is crucial for the brain to execute memory and learning functions. However, many questions remain regarding how pyramidal neurons (PNs) of the hippocampus mature and precisely position. Here we revealed that Setd2, the methyltransferase for histone 3 lysine 36 trimethylation (H3K36me3), is essential for the precise localization and maturation of PNs in the hippocampal CA1. The ablation of Setd2 in neural progenitors leads to irregular lamination of the CA1 and increased numbers of PNs in the stratum oriens. Setd2 deletion in postmitotic neurons causes mislocalization and immaturity of CA1 PNs. Transcriptome analyses revealed that SETD2 maintains the expressions of clustered protocadherin (cPcdh) genes. Together, Setd2 is required for proper hippocampal lamination and maturation of CA1 PNs.

Investigation of the role of sodium chloride on wheat starch multi-structure, physicochemical and digestibility properties during X-ray irradiation.

In this paper, different NaCl content was added to wheat starch and then subjected to X-ray irradiation to investigate the effect of salt on starch modification by irradiation. The results showed that the degradation of wheat starch intensified with the increase in irradiation dose. When irradiated at the same dose, wheat starch with sodium chloride produced shorter chains, lower molecular weight and amylose content, and higher crystallinity, solubility, and resistant starch than wheat starch without sodium chloride. The energy generated by X-rays dissociating sodium chloride caused damage to the glycoside bonds of the starch molecule. With a further increase in the mass fraction of NaCl, the hydrogen bonds of the starch molecules were broken, and the double helix structure was depolymerized, which exacerbated the extent of irradiation-modified wheat starch. At the same time, starch molecules will be rearranged to form a more stable structure.

Combined detection of serum IL-6 and CEA contributes to the diagnosis of lung adenocarcinoma in situ.

Background: Effective discrimination of lung adenocarcinoma (LUAD) in situ (AIS) from benign pulmonary nodules (BPN) is critical for the early diagnosis of AIS. Our pilot study in a small cohort of 90 serum samples has shown that serum interleukin 6 (IL-6) detection can distinguish AIS from BPN and health controls (HC). In this study, we intend to comprehensively define the diagnostic value of individual and combined detection of serum IL-6 related to the traditional tumor markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) for AIS. Methods: The diagnostic performance of serum IL-6 along with CEA and CYFRA21-1 were evaluated in a large cohort of 300 serum samples by a chemiluminescence immunoassay and an electrochemiluminescence immunoassay. A training set comprised of 65 AIS, 65 BPN, and 65 HC samples was used to develop the predictive model for AIS. Data obtained from an independent validation set was applied to evaluate and validate the predictive model. Results: In the training set, the levels of serum IL-6 and CEA in the AIS group were significantly higher than those in the BPN/HC group (P < 0.05). There was no significant difference in serum CYFRA21-1 levels between the AIS group and the BPN/HC group (P> 0.05). Serum IL-6 and CEA levels for AIS patients showed an area under the curve (AUC) of 0.622 with 23.1% sensitivity at 90.7% specificity, and an AUC of 0.672 with 24.6% sensitivity at 97.6% specificity, respectively. The combination of serum IL-6 and CEA presented an AUC of 0.739, with 60.0% sensitivity at 95.4% specificity. The combination of serum IL-6 and CEA showed an AUC of 0.767 for AIS patients, with 57.1% sensitivity at 91.4% specificity in the validation set. Conclusions: IL-6 shows potential as a prospective serum biomarker for the diagnosis of AIS, and the combination of serum IL-6 with CEA may contribute to increased accuracy in AIS diagnosis. However, it is worth noting that further research is still necessary to validate and optimize the diagnostic efficacy of these biomarkers and to address potential sensitivity limitations.

Engineered Luminescent Oncolytic Vaccinia Virus Activation of Photodynamic-Immune Combination Therapy for Colorectal Cancer.

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

Empowerment-Led Guided Self-Help Intervention for Symptom Burden in Breast Cancer Women Treated With Ovarian Function Suppression: A Randomized Trial Protocol.

Background: Ovarian function suppression (OFS) treatment causes breast cancer patients' estrogens to fall rapidly to postmenopausal levels, and the 5-year treatment duration and 28-day treatment cycles place a heavy physical and psychological symptom burden on them, which in turn directly or indirectly affects the survival benefit. Managing symptom burden early in treatment is critical, but OFS-related studies have yet to be seen. Self-management is essential for patients' symptom burden. However, self-help management is hampered by patients' lack of knowledge, skills, motivation, etc. Guided self-help intervention (GSH) provides a feasible approach. Empowerment theory is a promising theoretical framework to guide self-management. Methods: A prospective two-arm parallel randomized controlled single-blind clinical trial will be conducted to investigate the effect of symptom burden GSH based on empowerment theory in breast cancer patients in the early stages of OFS treatment. A block randomization method is used to allocate 144 patients to either the control or intervention group. The program is conducted according to the OFS return-to-hospital treatment cycle. The intervention group will receive a total of two rounds and five sessions of empowering GSH, lasting at least 15 weeks in total; the control group will receive only usual nursing care. Symptom burden and related metrics will be assessed at baseline and 1, 3, and 6 months after OFS treatment, and changes between and within groups will be explored. This paper adhered to the SPIRIT and CONSORT guidelines. Conclusion: These results will help to validate the GSH in symptom burden management for breast cancer patients in OFS treatment early stages. It enriches its symptom burden management research and may provide implications for the whole cycle of OFS treatment patients.

Effects of Salmonella Typhimurium Infection on the Gut Microbiota of Cherry Valley Meat Ducks.

Salmonella infection causes serious economic losses, threatens food safety, and is one of the most important diseases threatening meat duck farming. The gut microbiome is critical in providing resistance against colonization by exogenous microorganisms. Studying the relationship between Salmonella and gut microbiota can help us better understand the threat of the pathogenic mechanism of Salmonella and provide a more scientific theoretical basis for its prevention and treatment. This study uses Salmonella Typhimurium as the research object and Cherry Valley meat duck as the model with which to study the impact of Salmonella infection on ducks. In this field trial, 2 × 108 CFUs Salmonella Typhimurium were administered to 3-day-old ducks. After infection, duck viscera were collected to detect the colonization of Salmonella, and cecal contents were collected to analyze the changes in gut microbiota. The results show that Salmonella Typhimurium can colonize ducks three days after infection and alter the gut microbiota composition, mainly by increasing the abundance of Ruminococcaceae and Lachnospiraceae. In conclusion, Salmonella Typhimurium infection significantly alters the intestinal microbiota of ducks and poses a serious public health risk.

A midbrain GABAergic circuit constrains wakefulness in a mouse model of stress.

Enhancement of wakefulness is a prerequisite for adaptive behaviors to cope with acute stress, but hyperarousal is associated with impaired behavioral performance. Although the neural circuitries promoting wakefulness in acute stress conditions have been extensively identified, less is known about the circuit mechanisms constraining wakefulness to prevent hyperarousal. Here, we found that chemogenetic or optogenetic activation of GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus (DRNGAD2) decreased wakefulness, while inhibition or ablation of these neurons produced an increase in wakefulness along with hyperactivity. Surprisingly, DRNGAD2 neurons were paradoxically wakefulness-active and were further activated by acute stress. Bidirectional manipulations revealed that DRNGAD2 neurons constrained the increase of wakefulness and arousal level in a mouse model of stress. Circuit-specific investigations demonstrated that DRNGAD2 neurons constrained wakefulness via inhibition of the wakefulness-promoting paraventricular thalamus. Therefore, the present study identified a wakefulness-constraining role DRNGAD2 neurons in acute stress conditions.