Associations of weight control related behaviors with current cigarette smoking among Chinese adolescents: Results from an ongoing school-based survey in Zhejiang province.

INTRODUCTION: Previous studies have suggested that adolescents may smoke cigarettes to control weight, but relevant research is scarce in Chinese youth. This study was conducted to examine the associations of weight control related behaviors with cigarette smoking in Chinese students. METHODS: This was a secondary analysis of data for 24835 middle and high school students drawn from the 2022 Zhejiang Youth Risk Behavior Survey of China which collected self-reported information of cigarette smoking, weight control strategies and other health-related behaviors. Multivariable logistic regression models were used to estimate the adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for the study associations. RESULTS: Overall, there were 998 (4.02%) current cigarette smokers in this wave of the Zhejiang YRBS (2022). Neither trying to control weight nor healthy weight control behavior of exercising was associated with current cigarette smoking (AOR=1.15; 95% CI: 0.97-1.37 and AOR=1.01; 95% CI: 0.85-1.20, respectively). Meanwhile, unhealthy weight control behaviors of taking laxatives (AOR=1.52; 95% CI: 1.03-2.26), taking diet pills (AOR=1.82; 95% CI: 1.26-2.62), dieting (AOR=1.24; 95% CI: 1.04-1.49), and fasting (AOR=1.81; 95% CI: 1.40-2.34) were significantly associated with increased odds of current cigarette smoking. CONCLUSIONS: Screening and developing interventions for unhealthy weight control behaviors should be considered as part of smoking prevention programs among adolescents.

Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer.

Background: Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease. Materials and methods: Utilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated the cellular composition across six ovarian cancer patients with omental metastasis. Our focus centered on analysis of the malignant epithelial cells. Employing CytoTRACE and slingshot pseudotime analyses, we identified critical subpopulations and explored associated transcription factors (TFs) influencing ovarian cancer progression. Furthermore, by integrating clinical factors from a large cohort of bulk RNA sequencing data, we have established a novel prognostic model to investigate the impact of the tumor immune microenvironment on ovarian cancer patients. Furthermore, we have investigated the condition of immunological exhaustion. Results: Our study identified a distinct and highly proliferative subgroup of malignant epithelial cells, known as C2 TOP2A+ TCs. This subgroup primarily consisted of patients who hadn't received neoadjuvant chemotherapy. Ovarian cancer patients with elevated TOP2A expression exhibited heightened sensitivity to neoadjuvant chemotherapy (NACT). Moreover, the transcription factor MYBL2 in this subgroup played a critical role in ovarian cancer development. Additionally, we developed an independent prognostic indicator, the TOP2A TCs Risk Score (TTRS), which revealed a correlation between the High TTRS Group and unfavorable outcomes. Furthermore, immune infiltration and drug sensitivity analyses demonstrated increased responsiveness to Paclitaxel, Cisplatin, and Gemcitabine in the Low TTRS Group. Conclusion: This research deepens our understanding of malignant epithelial cells in ovarian cancer and enhances our knowledge of the ovarian cancer immune microenvironment and immune exhaustion. We have revealed the heightened susceptibility of the C2 TOP2A+ TCs subgroup to neoadjuvant chemotherapy and emphasized the role of MYBL2 within the C2 subgroup in promoting the occurrence and progression of ovarian cancer. These insights provide valuable guidance for the management of ovarian cancer treatment.

Heterogeneity of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells in mice.

OBJECTIVES: This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells (CNCs) in mice. METHODS: The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day (E)8.0-E9.25 were collected for histological observation. We performed immunostaining to compare green fluorescent protein (GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5. Single-cell RNA sequencing (scRNA-seq) was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5. Real time fluorescence quantitative polymerase chain reaction (q-PCR) was performed to validate the differential genes. RESULTS: Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch, respectively, at E8.0. Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues, the former had higher expression in palate and tongue. The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentiation and ossification, while Wnt1-Cre-marked CNCs participated in limb development, cell migration, and ossification. The q-PCR data also confirmed the results of gene ontology analysis. CONCLUSIONS: Pax2-Cre mice are perfect experimental animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.

A protective mechanism of heat inactivation to enhance Levilactobacillus brevis PDD-2 against alcohol-induced chronic liver disease based on proteomic analysis.

A proteomics-based analysis of the effect of heat inactivation on the alleviation of alcoholic liver disease (ALD) using Levilactobacillus brevis PDD-2 is presented, aimed at exploring the potential and mechanisms of postbiotic elements prepared through heat inactivation in the treatment of ALD. It was found that L. brevis PDD-2 and its postbiotic (heat-inactivated L. brevis PDD-2) alleviate chronic ALD via the gut-liver axis. In particular, heat-inactivated L. brevis PDD-2 significantly increased the relative abundance of Erysipelotrichaceae and better facilitated the oxidative stress balance in the liver. The tandem mass tag (TMT)-based quantitative proteomics technique analyses revealed that heat-inactivated L. brevis PDD-2 was associated with up-regulated expression levels of proteins related to the redox system, cellular metabolism, amino acid and oligopeptide transport, and surface proteins with immunomodulatory capacity. These findings provide a theoretical basis for developing novel therapeutic strategies and lay a solid foundation for further revealing its exhaustive mechanisms.

Association between sleep duration, suicidal ideation, suicidal attempt and suicidal behavior among Chinese adolescents.

BACKGROUND: A relatively small number of studies have researched the relationship between sleep duration and suicidal ideation, attempts, and behavior. This research aims to investigate the link between sleep duration and suicide in Chinese adolescents, and to examine the role of depression as a mediating factor. METHOD: Data were collected from 3315 students using a multi-stage random cluster sampling method and self-administered questionnaires. The study applied logistic regression to investigate the relationship between sleep duration and various forms of suicidal behavior, and mediation analysis to understand how depression might influence this relationship. RESULTS: The average sleep duration among the adolescents was 7.25 h (±0.20), with 59.67 % reporting insufficient sleep. The logistic regression analysis showed that longer sleep duration is linked with lower risks of suicidal ideation (OR: 0.753, 95%CI: 0.696 to 0.814), suicidal attempts (OR: 0.830, 95%CI: 0.748 to 0.922), and suicidal behavior (OR: 0.841, 95%CI: 0.713 to 0.992). Analysis using restricted cubic spline plots indicated the connection between sleep duration and these suicidal factors was not linear. The study found that depression plays a partial mediating role between sleep duration and suicidal ideation, with an effect of 52.29 %. LIMITATIONS: The cross-sectional study design could not prove causation. CONCLUSIONS: There is a clear non-linear association between sleep duration and suicidal tendencies in adolescents, with depression acting as a mediator. This suggests that future research could focus on sleep and mood management as ways to address suicide risk in this age group.

Targeting Metabolic-Redox Nexus to Regulate Drug Resistance: From Mechanism to Tumor Therapy.

Drug resistance is currently one of the biggest challenges in cancer treatment. With the deepening understanding of drug resistance, various mechanisms have been revealed, including metabolic reprogramming and alterations of redox balance. Notably, metabolic reprogramming mediates the survival of tumor cells in harsh environments, thereby promoting the development of drug resistance. In addition, the changes during metabolic pattern shift trigger reactive oxygen species (ROS) production, which in turn regulates cellular metabolism, DNA repair, cell death, and drug metabolism in direct or indirect ways to influence the sensitivity of tumors to therapies. Therefore, the intersection of metabolism and ROS profoundly affects tumor drug resistance, and clarifying the entangled mechanisms may be beneficial for developing drugs and treatment methods to thwart drug resistance. In this review, we will summarize the regulatory mechanism of redox and metabolism on tumor drug resistance and highlight recent therapeutic strategies targeting metabolic-redox circuits, including dietary interventions, novel chemosynthetic drugs, drug combination regimens, and novel drug delivery systems.

Air pollution and cancer daily mortality in Hangzhou, China: an ecological research.

BACKGROUND: Long-term exposure to air pollution has been linked to cancer incidence. However, the evidence is limited regarding the effect of short-term exposure to air pollution on cancer mortality. OBJECTIVES: This study aimed to investigate associations between short-term exposure to air pollutants (sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <10 mm (PM10) and PM2.5) and cancer daily mortality. METHODS: This study used air quality, meteorological and daily cancer death data from 2014 to 2019 in Hangzhou, China. Generalised additive models (GAM) with quasi-Poisson regression were used to analyse the associations between air pollutants and cancer mortality with adjustment for confounding factors including time trends, day of week, temperature and humidity. Then, we conducted stratified analyses by sex, age, season and education. In addition, stratified analyses of age, season and education were performed within each sex to determine whether sex difference was modified by such factors. RESULTS: After adjusting for potential confounders, the GAM results indicated a statistically significant relationship between increased cancer mortality and elevated air pollution concentrations, but only in the female population. For every 10 µg/m3 rise in pollutant concentration, the increased risk of cancer death in females was 6.82% (95% CI 3.63% to 10.10%) for SO2 on lag 03, and 2.02% (95% CI 1.12% to 2.93%) for NO2 on lag 01 and 0.89% (95% CI 0.46% to 1.33%) for PM10 on lag 03 and 1.29% (95% CI 0.64% to 1.95%) for PM2.5 on lag 03. However, no statistically significant association was found among males. Moreover, the differences in effect sizes between males and females were more pronounced during the cold season, among the elderly and among subjects with low levels of education. CONCLUSIONS: Increased cancer mortality was only observed in females with rising concentrations of air pollutants. Further research is required to confirm this sex difference. Advocate for the reduction of air pollutant emissions to protect vulnerable groups.

Association between pulse pressure and carotid plaques in old adults with uncontrolled hypertension: results from a community-based screening in Hangzhou, China.

BACKGROUND: There is a broad pulse pressure (PP) and a high prevalence of carotid plaques in old adults. Previous studies have indicated that PP is strongly associated with carotid plaque formation. This study aimed to explore this association in old adults with uncontrolled hypertension. METHODS: 1371 hypertensive patients aged ≥ 60 years with uncontrolled hypertension were enrolled in a community-based screening in Hangzhou, China. Carotid plaques were assessed using ultrasonography. Logistic regression models were used to estimate the association between PP and carotid plaques by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Carotid plaques were detected in 639 (46.6%) of subjects. Multiple plaques were found in 408 (63.8%) and soft plaques in 218 (34.1%). Elevated PP was associated with a high prevalence of carotid plaques. After adjusting for traditional risk factors, compared to patients within the lowest tertile of PP, those within the highest tertiles had an increased risk of carotid plaques (OR 2.061, CI 1.547-2.745). For each 1-SD increase, the risk increased by 40.1% (OR 1.401, CI 1.237-1.587). There was a nonlinear association between PP and carotid plaques (P nonlinearity = 0.039). The risk increased rapidly after the predicted PP level reached around 60 mmHg. The associations were stronger among participants with multiple and soft plaques. CONCLUSIONS: Our findings suggested that PP was independently associated with carotid plaques in old adults with uncontrolled hypertension who have an increased risk of atherosclerosis.

Remnant cholesterol and the risk of carotid plaque in hypertension: results from a community-based screening among old adults in Hangzhou, China.

Elevated remnant cholesterol (RC) is considered a risk factor for atherosclerotic cardiovascular disease, but the evidence on this association applies to the Chinese population with hypertension is limited. We aimed to explore the association between RC levels and carotid plaque in old adults with hypertension. 8523 hypertensive patients aged ≥ 60 years with serum lipids and carotid ultrasonography data were included in this community-based screening. Fasting RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDLC). The associations of RC levels with carotid plaque risk were evaluated using Logistic regression and restricted cubic spline models. Carotid plaque was screened in 4821 (56.56%) subjects. After multivariable-adjusted, RC was significantly related to carotid plaque [Odd ratio (OR)] = 1.043 per 0.1 mmol/L increase, 95% confidence interval (CI): 1.030-1.056). The highest versus the lowest quartile of RC was 1.928 (1.673-2.223) for carotid plaque. A nonlinear association was found between serum RC levels and the risk of carotid plaque (P for nonlinearity < 0.001). Moreover, an RC > 0.78 mmol/L differentiated patients at a higher risk of carotid plaque compared to those at lower concentrations, regardless of whether LDLC was on target at 2.59 mmol/L. In old adults with hypertension, elevated RC was positively associated with carotid plaque, independent of LDLC and other conventional risk factors.

Riding practices of e-bike riders after the implementation of electric bike management regulations: An observational study in Hangzhou, China.

Objective: This study aimed to understand the riding behaviors of electric bike (e-bike) users in Hangzhou after the "Regulations of Zhejiang Province on the Administration of Electric Bicycles". Methods: The study consisted of two parts, including a questionnaire survey of local e-bike users in Shangcheng District and Jiande County in Hangzhou City, and a cross-sectional observational study of 16 intersections. Results: A total of 789 e-bike riders participated in the questionnaire survey, and the riding behavior of 99,407 e-bike users was observed. The main purpose of using e-bike was work and daily life, 46.0% of them used e-bikes more than 5 days a week, and 58.5% used e-bikes for less than 30 min each time. A vast majority (81.7%) of e-bike riders believe that the implementation of Zhejiang Regulations has significantly improved the safety level of e-bike riding in the region. The field survey found that the correct rates of helmet wearing by e-bike riders and passengers were 78.83% and 42.27%. The main violations were invalid/non-helmet wearing (21.17%), followed by carrying passengers and running red lights (7.94% and 4.26%). The rates of invalid/non-helmet wearing and running red lights were significantly higher during non-morning rush hour, weekends, and roads without separate non-motorized vehicle lanes than in other conditions (all P < 0.05). Additionally, sunny days and crossroads were risk factors for passenger-carrying and invalid/non-helmet wearing compared to rainy/cloudy days and T-intersections. Conclusions: The phenomenon that e-bike users' correct practice lags far behind the awareness of various violations has shown some improvement. To further enhance safety measures for e-bike riders, it is necessary to promote education, improve infrastructure, and strengthen law enforcement, in support of the "Zhejiang Regulations" and behavioral interventions.

Increased incidence risks of cardiovascular disease among cancer patients: Evidence from a population-based cohort study in China.

BACKGROUND: Cardiovascular disease (CVD) is becoming a major concern among cancer patients, leading to the development of a new field named cardio-oncology. However, previous studies were mainly based on the western population and focused on CVD mortality. Evidence from the Chinese population is limited. Furthermore, few studies investigated the incidence risks of CVD among cancer patients. METHODS: 85,787 eligible cancer patients were included from Hangzhou city, China. Age-standardized standard incidence ratio (SIR) was used to reflect the incidence risks of CVD among cancer patients as compared with the standard population, which was defined as all residents in Hangzhou city during the same period. RESULTS: After three years of follow-up, cancer patients showed elevated incidence risks of CVD (SIR = 1.41, 95%CI: 1.35-1.47) as compared with the standard population. The elevated risks of CVD were highest in the first year after cancer diagnosis (SIR = 1.68, 95%CI: 1.58-1.78), then followed by the second (SIR = 1.21, 95%CI: 1.11-1.31) and the third (SIR = 1.18, 95%CI: 1.07-1.29) year. These results were consistent in males and females. Furthermore, different risks of CVD were observed among different cancer sites. Patients with pancreatic cancer showed the highest risks of CVD, then followed by liver cancer, lung cancer, kidney cancer, gastric cancer, bladder cancer, prostate cancer, and colorectal cancer. CONCLUSIONS: Cancer patients have increased incidence risks of CVD, especially in the first year after cancer diagnosis. The increased risks of CVD vary by different cancer sites. Our findings highlight the importance of paying close attention to the CVD risks among cancer patients.

Recent Advances on Antimicrobial Peptides from Milk: Molecular Properties, Mechanisms, and Applications.

Traditional antibiotics are facing a tremendous challenge due to increased antimicrobial resistance; hence, there is an urgent need to find novel antibiotic alternatives. Milk protein-derived antimicrobial peptides (AMPs) are currently attracting substantial attention considering that they showcase an extensive spectrum of antimicrobial activities, with slower development of antimicrobial resistance and safety of raw materials. This review summarizes the molecular properties, and activity mechanisms and highlights the applications and limitations of AMPs derived from milk proteins comprehensively. Also the analytical technologies, especially bioinformatics methodologies, applied in the process of screening, identification, and mechanism illustration of AMPs were underlined. This review will give some ideas for further research and broadening of the applications of milk protein-derived AMPs in the food field.

The whole-blood Epstein-Barr virus DNA can serve as a valuable molecular marker for diagnosis and prognosis prediction of nasopharyngeal carcinoma.

The clinical significance and prognostic role of whole-blood EBV-DNA in EBV-associated nasopharyngeal carcinoma (NPC) have not been thoroughly investigated. This study aims to explore the diagnostic and prognostic value of EBV-DNA for NPC in a non-endemic region of China. We enrolled patients with chronic active EBV infection (CAEBV), nasopharyngitis (NA), extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT), and NPC. Demographic and clinical data were collected and the diagnostic and prognostic values of EBV-DNA were analyzed. Immunohistochemistry was performed to detect EBV-encoded small ribonucleic acids (EBER), as well as the expression of p53, Ki-67, and epidermal growth factor receptor (EGFR). The levels of pretreatment Epstein-Barr virus DNA (preEBV-DNA) in new NPC cases were found to differ from those in other diseases and exhibited varying age distributions. The threshold value of preEBV-DNA for distinguishing NPC from CAEBV and NA was determined. We confirmed that epistaxis, diabetes mellitus, T3N2 or T4N0-2 stage, and IgM positivity were associated with higher levels of preEBV-DNA, and identified risk factors associated with the prognosis of locoregionally advanced NPC (La-NPC). Patients with intermittently or persistently positive EBV-DNA (IPCP), higher preEBV-DNA levels, and positive Epstein-Barr virus-encoded small RNA (EBER) status (EBERpos) had worse survival. New cases of NPC with elevated levels of EBV in the whole-blood and positive EBER status were shown to have a poor prognosis upon progression to La-NPC. EBV-DNA was found to be an indicator for predicting prognosis in La-NPC and could also be used to distinguish new NPC cases.

SMAD7 gene polymorphisms and their influence on patients with colorectal cancer.

Colorectal cancer (CRC) is a prevalent malignant tumor, and its pathogenesis is still not fully understood. Studies have shown that SMAD7 gene polymorphisms can affect CRC susceptibility, but the results have been inconsistent and require additional confirmation. Our study aimed to evaluate the effect of SMAD7 variants on the risk of CRC in the Chinese Han population. A total of five single nucleotide polymorphisms (SNPs) in SMAD7 were genotyped among 696 CRC patients and 696 healthy participants using the MassARRAY iPLEX platform. SNPs were evaluated for their associations with CRC using logistic regression analysis under multiple genetic models. The false-positive report probability (FPRP) analysis was used to validate the positive findings. Our study indicated that rs11874392 showed an increased association with CRC risk (odds ratio, 1.31; 95% confidence interval, 1.04-1.67; p = 0.024). Stratified analysis showed that rs11874392 might increase the risk of CRC in females (OR = 1.70, p = 0.028), individuals with smoking (OR = 1.87, p = 0.026), and drinking (OR = 1.38, p = 0.027). The rs11874392 was found to be related to an elevated risk of rectal cancer (OR = 1.73, p = 0.003), but not with colon cancer. FPRP analysis demonstrated that all of these associations were statistically significant (FPRP <0.2). Additionally, rs11874392 was the strongest predictive model for CRC. This study provides evidence that the SMAD7 rs11874392 is related to an increased susceptibility to CRC.

Upregulated TC1 and downregulated Chibby were correlated with the aberrant ß-catenin expression in laryngeal squamous cell carcinoma.

As an important member of Wnt/ß-catenin signaling pathway, the aberrant expression of ß-catenin has been implicated in many cancers. Chibby, a ß-catenin binding partner, is an antagonist involved in this pathway. In contrast, thyroid cancer 1 (TC1) as an activator of this pathway can relieve the antagonistic activity of Chibby on the ß-catenin-mediated transcription and is high expressed in human tumors. The objectives of this study were to examine the expression of TC1, Chibby, and ß-catenin and investigate the association among them in laryngeal squamous cell carcinoma (LSCC). The expression of TC1, Chibby, ß-catenin, c-Myc, Cyclin D1, and matrix metalloproteinase-7 (MMP-7) were examined by immunohistochemistry in samples from 53 LSCC patients. Compared with normal laryngeal squamous epithelium (NLSE), there were upregulated expression of TC1, downregulated expression of Chibby, and aberrant cytoplasmic expression of ß-catenin in the LSCC tissues (P < .001). The high expression of TC1 was correlated with the tumor site, advanced TNM and T stage, lymphovascular invasion, and poor differentiation in LSCC tissues (P < .050). There were correlations between the aberrant expression of ß-catenin and the tumor site, advanced TNM and T stage, lymphovascular invasion, perineurial invasion, and poor differentiation in LSCC tissues (P < .050). Upregulated TC1 and downregulated Chibby were correlated with aberrant expression of ß-catenin (P < .001), but no correlation between them (P = .076). The percent of abnormal expression of ß-catenin in LSCC was 96.00% in TC1+/Chibby-, 73.68% in TC1+/Chibby+, 0.00% in TC1-/Chibby-, and 0.00% in TC1-/Chibby + group (P < .001). High expression of c-Myc, Cyclin D1, and MMP-7 was observed in LSCC tissues (P < .001). There was statistically significant about the expression of Cyclin D1 and MMP-7 among the groups of TC1+/Chibby-, TC1+/Chibby+, TC1-/Chibby-, and TC1-/Chibby + (P < .001), but was not significance about the expression of c-Myc among them (P = .339). No association was found between overall survival and the expression of TC1, Chibby, and ß-catenin (P > .05). The upregulated expression of TC1 and downregulated expression of Chibby were correlated with the aberrant expression of ß-catenin and the high expression of Cyclin D1 and MMP-7 in LSCC tissues.

Screening of an efficient cholesterol-lowering strain of Lactiplantibacillus plantarum 54-1 and investigation of its degradation molecular mechanism.

In this study, an efficient cholesterol-lowering strain of Lactiplantibacillus plantarum 54-1 was screened and its degradation molecular mechanism was investigated. Furthermore, a novel practical MRS medium for screening cholesterol-lowering lactic acid bacteria (LAB) was developed based on ultrasound treatment. L. plantarum 54-1 was found to have the highest ability to eliminate cholesterol (340.69 ± 5.87 µg/mL). According to SEM and the count of viable LAB results, the morphology of LAB in the cholesterol-containing medium developed in this experiment was close to the normal (full and smooth), and it can grow normally. Metabolomics revealed that L. plantarum 54-1 initially converted a portion of cholesterol to 7α-hydroxy-cholesterol and then to the key metabolite taurine, via the phosphotransferase system. These metabolites were further transformed into L-alanine, L-lysine, N6-Acetyl-L-lysine, (R)-b-aminoisobutyric acid, and 2-oxoarginine, through glycine, serine, and threonine metabolism, citrate cycle, D-arginine and D-ornithine metabolism, lysine degradation, and pyruvate metabolism pathways. Prokaryotic reference transcriptomics found that this may be mainly regulated by the bsh, phnE, ptsP, B0667_RS04545, and B0667_RSRS12300 genes, which was further validated by qPCR. Furthermore, molecular docking results demonstrated that 8 differential metabolites might bind to another portion of cholesterol via PI-PI conjugation and hydrophobic interactions and lower cholesterol via co-sedimentation. This study has strategic implications for developing probiotic powder food that lowers cholesterol.

STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia.

Immunotherapy is a revolutionized therapeutic strategy for tumor treatment attributing to the rapid development of genomics and immunology, and immune checkpoint inhibitors have successfully achieved responses in numbers of tumor types, including hematopoietic malignancy. However, acute myeloid leukemia (AML) is a heterogeneous disease and there is still a lack of systematic demonstration to apply immunotherapy in AML based on PD-1/PD-L1 blockage. Thus, the identification of molecules that drive tumor immunosuppression and stratify patients according to the benefit from immune checkpoint inhibitors is urgently needed. Here, we reported that STAT5 was highly expressed in the AML cohort and activated the promoter of glycolytic genes to promote glycolysis in AML cells. As a result, the increased-lactate accumulation promoted E3BP nuclear translocation and facilitated histone lactylation, ultimately inducing PD-L1 transcription. Immune checkpoint inhibitor could block the interaction of PD-1/PD-L1 and reactive CD8+ T cells in the microenvironment when co-culture with STAT5 constitutively activated AML cells. Clinically, lactate accumulation in bone marrow was positively correlated with STAT5 as well as PD-L1 expression in newly diagnosed AML patients. Therefore, we have illustrated a STAT5-lactate-PD-L1 network in AML progression, which demonstrates that AML patients with STAT5 induced-exuberant glycolysis and lactate accumulation may be benefited from PD-1/PD-L-1-based immunotherapy.

Protection Mechanism of Metal Ion Pre-Stress on Lactobacillus acidophilus CICC 6074 under Acid Tolerance.

The prerequisite for the probiotic effect of lactic acid bacteria is that they could survive the acid stress environment of production and application. In this experiment, the mechanism for the effect of different metal ion pre-stress on the acid-tolerant survival of Lactobacillus was investigated. Scanning electron microscopy, Fourier infrared spectroscopy, and flow cytometry were used to analyze the condition of bacteria after acid treatment, which revealed that different metal ion pre-stress could improve the survival ability of Lactobacillus acidophilus CICC 6074 under low acid conditions by improving cell morphology, mitigating cell membrane damage, and regulating surface protein expression. Furthermore, Tandem Mass Tags (TMT) proteomic analysis revealed that Mn2+ pre-stress showed relatively more superior protective effects on acid tolerance in L. acidophilus CICC 6074 through activation of DNA replication, RNA synthesis, S-layer protein secretion, H+-ATPase enzyme activity, etc. This study will provide new ideas and a theoretical basis for the development and application of lactic acid bacteria.

Disruption of mitochondrial oxidative phosphorylation by chidamide eradicates leukemic cells in AML.

PURPOSE: Nowadays, the oxidative phosphorylation (OXPHOS) correlated with leukemogenesis and treatment response is extensive. Thus, exploration of novel approaches in disrupting OXPHOS in AML is urgently needed. MATERIALS AND METHODS: Bioinformatical analysis of TCGA AML dataset was performed to identify the molecular signaling of OXPHOS. The OXPHOS level was measured through a Seahorse XFe96 cell metabolic analyzer. Flow cytometry was applied to measure mitochondrial status. Real-time qPCR and western blot were used to analyze the expression of mitochondrial or inflammatory factors. MLL-AF9-induced leukemic mice were conducted to measure the anti-leukemia effect of chidamide. RESULTS: Here, we reported that AML patients with high OXPHOS level were in a poor prognosis, which was associated with high expression of HDAC1/3 (TCGA). Inhibition of HDAC1/3 by chidamide inhibited cell proliferation and induced apoptotic cell death in AML cells. Intriguingly, chidamide could disrupt mitochondrial OXPHOS as assessed by inducing mitochondrial superoxide and reducing oxygen consumption rate, as well as decreasing mitochondrial ATP production. We also observed that chidamide augmented HK1 expression, while glycolysis inhibitor 2-DG could reduce the elevation of HK1 and improve the sensitivity of AML cells exposed to chidamide. Furthermore, HDAC3 was correlated with hyperinflammatory status, while chidamide could downregulate the inflammatory signaling in AML. Notably, chidamide eradicated leukemic cells in vivo and prolonged the survival time of MLL-AF9-induced AML mice. CONCLUSION: Chidamide disrupted mitochondrial OXPHOS, promoted cell apoptosis and reduced inflammation in AML cells. These findings exhibited a novel mechanism that targeting OXPHOS would be a novel strategy for AML treatment.

Characterization of the effects of binary probiotics and wolfberry dietary fiber on the quality of yogurt.

The effects of binary probiotics (Lacticaseibacillus casei CGMCC1.5956 and Lactiplantibacillus plantarum subsp. plantarum CGMCC 1.5953) in conjunction with wolfberry dietary fiber (WDF) on yogurt quality were investigated in this study. d-fructose, ß-d-glucose, 6-acetyl-d-glucose, and 1-ketose in WDF significantly improved syneresis, apparent viscosity, and elastic behavior of yogurt. Binary probiotics were more suitable for fermenting WDF yogurt than single probiotics, resulting in a higher viable count (9.39 lg (CFU/mL)) and unique flavor. Binary probiotics can promote the production of tyrosol by L. casei 56 through the tyrosine metabolic pathway, thereby enhancing the resistance of L. casei 56 and L. plantarum 53 to their environment and promoting growth. Pyridine, 2,3,4,5-tetrahydro- and prenol might be responsible for the high odor scores in the sensory evaluation of WDF yogurt prepared using binary probiotics. In summary, combining binary probiotics and WDF can significantly improve yogurt quality and add value to the final product.