Precision therapy for ulcerative colitis: insights from mitochondrial dysfunction interacting with the immune microenvironment.

Background: Accumulating evidence reveals mitochondrial dysfunction exacerbates intestinal barrier dysfunction and inflammation. Despite the growing knowledge of mitochondrial dysfunction and ulcerative colitis (UC), the mechanism of mitochondrial dysfunction in UC remains to be fully explored. Methods: We integrated 1137 UC colon mucosal samples from 12 multicenter cohorts worldwide to create a normalized compendium. Differentially expressed mitochondria-related genes (DE-MiRGs) in individuals with UC were identified using the "Limma" R package. Unsupervised consensus clustering was utilized to determine the intrinsic subtypes of UC driven by DE-MiRGs. Weighted gene co-expression network analysis was employed to investigate module genes related to UC. Four machine learning algorithms were utilized for screening DE-MiRGs in UC and construct MiRGs diagnostic models. The models were developed utilizing the over-sampled training cohort, followed by validation in both the internal test cohort and the external validation cohort. Immune cell infiltration was assessed using the Xcell and CIBERSORT algorithms, while potential biological mechanisms were explored through GSVA and GSEA algorithms. Hub genes were selected using the PPI network. Results: The study identified 108 DE-MiRGs in the colonic mucosa of patients with UC compared to healthy controls, showing significant enrichment in pathways associated with mitochondrial metabolism and inflammation. The MiRGs diagnostic models for UC were constructed based on 17 signature genes identified through various machine learning algorithms, demonstrated excellent predictive capabilities. Utilizing the identified DE-MiRGs from the normalized compendium, 941 patients with UC were stratified into three subtypes characterized by distinct cellular and molecular profiles. Specifically, the metabolic subtype demonstrated enrichment in epithelial cells, the immune-inflamed subtype displayed high enrichment in antigen-presenting cells and pathways related to pro-inflammatory activation, and the transitional subtype exhibited moderate activation across all signaling pathways. Importantly, the immune-inflamed subtype exhibited a stronger correlation with superior response to four biologics: infliximab, ustekinumab, vedolizumab, and golimumab compared to the metabolic subtype. Conclusion: This analysis unveils the interplay between mitochondrial dysfunction and the immune microenvironment in UC, thereby offering novel perspectives on the potential pathogenesis of UC and precision treatment of UC patients, and identifying new therapeutic targets.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Unlocking the predictive potential of long non-coding RNAs: a machine learning approach for precise cancer patient prognosis.

The intricate web of cancer biology is governed by the active participation of long non-coding RNAs (lncRNAs), playing crucial roles in cancer cells' proliferation, migration, and drug resistance. Pioneering research driven by machine learning algorithms has unveiled the profound ability of specific combinations of lncRNAs to predict the prognosis of cancer patients. These findings highlight the transformative potential of lncRNAs as powerful therapeutic targets and prognostic markers. In this comprehensive review, we meticulously examined the landscape of lncRNAs in predicting the prognosis of the top five cancers and other malignancies, aiming to provide a compelling reference for future research endeavours. Leveraging the power of machine learning techniques, we explored the predictive capabilities of diverse lncRNA combinations, revealing their unprecedented potential to accurately determine patient outcomes.

lncRNAs play crucial roles in cancer biology, regulating proliferation, migration, and drug resistance.Emerging evidence suggests that machine learning can predict cancer prognosis using specific lncRNA combinations.Comprehensive information on the predictive abilities of lncRNA combinations in oncology concerning machine learning is lacking.This review offers up-to-date vital references on diverse lncRNA combinations pertinent to future research and clinical trials.

Identification and Validation of a Novel Glycolysis-Related Gene Signature for Predicting the Prognosis and Therapeutic Response in Triple-Negative Breast Cancer.

INTRODUCTION: A high malignancy rate and poor prognosis are common problems with triple-negative breast cancer (TNBC). There is increasing evidence that glycolysis plays vital roles in tumorigenesis, tumor invasion, immune evasion, chemoresistance, and metastasis. However, a comprehensive analysis of the diagnostic and prognostic significance of glycolysis in TNBC is lacking. METHODS: Transcriptomic and clinical data of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, respectively. Glycolysis-related genes (GRGs) were collected from the Molecular Signatures Database (MSigDB). Differential comparative analysis was performed to obtain the differentially expressed (DE)-GRGs associated with TNBC. Based on the DE-GRGs, a glycolysis-related risk signature was established using Least Absolute Shrinkage and Selector Operation (LASSO) and multivariable Cox regression analyses. The prognostic value, tumor microenvironment, mutation status, and chemotherapy response of different risk groups were analyzed. An independent cohort from the METABRIC database was used for external validation. Furthermore, the expression patterns of five genes derived from the prognostic model were validated by quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: The glycolysis-related prognostic signature included five genes (IFNG, ACSS2, IRS2, GFUS, and GAL3ST1) and predicted the prognosis of TNBC patients independent of clinical factors (p < 0.05). Patients were divided into high- and low-risk groups based on the median risk score. Compared to low-risk TNBC patients, high-risk patients had significantly decreased overall survival (HR = 2.718, p < 0.001). Receiver operating characteristic and calibration curves demonstrated that the model had high performance in terms of predicting survival and risk stratification. The results remained consistent after external verification. Additionally, the tumor immune microenvironment significantly differed between the risk groups. Low-risk TNBC patients had a better immunotherapy response than high-risk patients. High-risk TNBC patients with a poor prognosis may benefit from targeted therapy. CONCLUSIONS: This study developed a novel glycolysis and prognosis-related (GRP) signature based on GRGs to predict the prognosis of TNBC patients, and may aid clinical decision-making for these patients.

Mitochondrial Dysfunction in Arrhythmia and Cardiac Hypertrophy.

Arrhythmia and cardiac hypertrophy are two very common cardiovascular diseases that can lead to heart failure and even sudden death, thus presenting a serious threat to human life and health. According to global statistics, nearly one million people per year die from arrhythmia, cardiac hypertrophy and other associated cardiovascular diseases. Hence, there is an urgent need to find new treatment targets and to develop new intervention measures. Recently, mitochondrial dysfunction has been examined in relation to heart disease with a view to lowering the incidence of arrhythmia and cardiac hypertrophy. The heart is the body's largest energy consuming organ, turning over about 20 kg of adenosine triphosphate (ATP) per day in the mitochondria. Mitochondrial oxidative phosphorylation (OXPHOS) produces up to 90% of the ATP needed by cardiac muscle cells for contraction and relaxation. Dysfunction of heart mitochondria can therefore induce arrhythmia, cardiac hypertrophy and other cardiovascular diseases. Mitochondrial DNA (mtDNA) mutations cause disorders in OXPHOS and defects in the synthesis of muscle contraction proteins. These lead to insufficient production of secondary ATP, increased metabolic requirements for ATP by the myocardium, and the accumulation of reactive oxygen species (ROS). The resulting damage to myocardial cells eventually induces arrhythmia and cardiac hypertrophy. Mitochondrial damage decreases the efficiency of energy production, which further increases the production of ROS. The accumulation of ROS causes mitochondrial damage and eventually leads to a vicious cycle of mitochondrial damage and low efficiency of mitochondrial energy production. In this review, the mechanism underlying the development of arrhythmia and cardiac hypertrophy is described in relation to mitochondrial energy supply, oxidative stress, mtDNA mutation and Mitochondrial dynamics. Targeted therapy for arrhythmia and cardiac hypertrophy induced by mitochondrial dysfunction is also discussed in terms of its potential clinical value. These strategies should improve our understanding of mitochondrial biology and the pathogenesis of arrhythmia and cardiac hypertrophy. They may also identify novel strategies for targeting mitochondria in the treatment of these diseases.

Association between Dietary Protein Intake and Type 2 Diabetes Mellitus in Chinese Rural Elderly Population: A Matched Case-Control Study.

The purpose of this study was to examine the association between dietary protein intake and the risk of type 2 diabetes mellitus (T2DM) among a Chinese rural elderly population. We used the demographic and dietary information of adults over age 65 in the Henan Rural Cohort Study to identify and pair 950 T2DM patients with healthy controls in a 1 : 1 matched case-control study. Dietary data was collected through a Food Frequency Questionnaire. A multivariate logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of T2DM risk according to protein intake. After adjustment for confounding factors, higher intake of total protein was negatively associated with T2DM risk in the total population (extreme-tertile OR=0.75, 95% CI: 0.58-0.93) and women (extreme-tertile OR=0.84, 95% CI: 0.47-0.93). Multivariate-adjusted ORs for the risk of T2DM in the highest compared with lowest tertile of plant protein intake in the total population and in women were 0.86 (95% CI: 0.60-0.84) and 0.58 (95% CI: 0.36-0.95), respectively. Our results suggest that the protein intake, especially plant protein, has a significant association with the risk of T2DM in rural elderly populations, and the sources of protein may be also important in future guidelines.

Shuanghua decoction exerts anticancer activity by activating NLRP3 inflammasome via ROS and inhibiting NF-κB signaling in hepatocellular carcinoma cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major subtype of liver cancer, with a high mortality rate, and close relation to chronic hepatitis. The components of the NLRP3 inflammasome are poorly expressed or even lost in HCC. Downregulation of the NLRP3 inflammasome expression significantly affects the clinical stages and pathological grade of HCC. According to previous research, Shuanghua decoction (SHD), a traditional folk prescription, has an inhibitory effect on nasopharyngeal cancer. PURPOSE: This study aimed to reveal the therapeutic potential of the traditional folk recipe, SHD and its demolition recipe for HCC, and to explore the underlying mechanism. METHODS: The effect of SHD and its demolition recipe on HCC cell biological behaviors was assessed using the MTT assay, colony formation, LDH release assay, KFluor-Edu staining, annexin V-FITC/PI staining assay, Hoechst staining, wound-healing assay, transwell assay, reactive oxygen species (ROS) release assay, HPLC, nude mice model, HE staining, IHC, western blot, and immunofluorescence staining in vitro and in vivo. RESULTS: SHD was found to inhibit HCC, and Oldenlandia and OP (Oldenlandia: Prunella spike = 2.5:1) were identified as the main ingredients that inhibited the proliferation and migration of HCC cells via the activation of the ROS-mediated NLRP3 inflammasome and inhibition of the NF-κB signaling pathway in vitro and in vivo. CONCLUSION: Overall, Chinese medicine theory and pharmacology research revealed that SHD, Oldenlandia and OP may be promising traditional Chinese medicine for the treatment of HCC.

Association of sleep duration with risk of type 2 diabetes mellitus in a rural Chinese population: a nested case-control study.

PURPOSE: To investigate the association of sleep duration with type 2 diabetes mellitus (T2DM) in a rural Chinese population. METHODS: A 1:1 matched nested case-control study was performed based on a cohort that had been established in rural communities in Henan Province, China. T2DM patients and healthy controls (550 pairs) were included in this study. RESULTS: Abnormal sleep duration significantly increased the risk of T2DM with an approximate U-shaped association (sleep duration ≤ 6 h, OR = 1.742, 95% CI = 1.007-3.011, P = 0.047; sleep duration 8-9 h, OR = 1.462, 95% CI = 1.038-2.060, P = 0.030) compared with participants with a night sleep duration of 7-8 h, after adjusting for multiple confounders. When stratified by gender, only women were sensitive to shorter sleep duration (OR = 2.483, 95% CI = 1.149-5.366, P = 0.021). Abnormal sleep duration (too short or too long) had adverse effects on homeostasis model assessment (HOMA) and blood metabolites, and the effect was more noticeable in people with longer sleep durations. CONCLUSION: In a rural Chinese population, both too short and too long sleep duration increased the risk of T2DM. Especially women with less sleep duration have a higher risk of T2DM. Abnormal sleep also affects the HOMA index and metabolites; the relationship between HOMA-IR, total cholesterol, and LDL-Cholesterol with sleep duration was U-shaped, while fasting plasma glucose, body mass index, waist circumference, and triglyceride levels increased significantly only with longer sleep duration.

Efficacy of programmed cell death protein 1 inhibitor in resection transformation treatment of esophageal cancer.

BACKGROUND: Surgery is an important component in the treatment of esophageal cancer. For patients not eligible for R0 resection, defined as locally advanced unresectable esophageal cancer, a new approach is to transform the cancer into a resectable state by preoperative treatment. However, preoperative chemo/radiation is unsatisfactory. Therefore, the aim of this study was to assess the safety and efficacy of chemo/radiotherapy combined with a programmed cell death protein 1 (PD-1) inhibitor in the preoperative transformation of unresectable esophageal cancer. METHODS: Patients were evaluated as having unresectable, locally advanced esophageal cancer at baseline and were re-evaluated as possible R0 resection candidates after PD-1 inhibitor treatment. Patient data were derived from the prospective database of Peking University Cancer Hospital Thoracic Surgery I. Preoperative chemotherapy plus PD-1 inhibitor treatment was defined as "transformation treatment." The objective response rate, operation rate (proportion of patients who underwent surgery), R0 rate, and treatment safety were analyzed retrospectively. RESULTS: A total of 36 patients were enrolled into the study, and 94.4% (34/36) completed the planned transformation treatment. The objective response rate was 71.4% (25/35), and 75% (27/36) of the patients who completed transformation treatment underwent surgery. For these surgical patients, 81.5% (22/27) obtained R0 resection, and 22.2% (6/22) had pathological complete response (pCR). During transformation treatment, 22.2% (8/36) patients had ≥ grade 3 complications. There were no reoperations or perioperative deaths. After surgery, 29.6% (8/27) had ≥ grade 3 complications. CONCLUSIONS: Esophagectomy after immunotherapy is safe with acceptable complications. Compared with chemotherapy alone, chemotherapy combined with immunotherapy had a more favorable transformation effect for patients with unresectable esophageal cancer.

Association of plant-based diet and type 2 diabetes mellitus in Chinese rural adults: The Henan Rural Cohort Study.

AIMS/INTRODUCTION: Studies have found that a plant-based diet was associated with a lower risk of type 2 diabetes, but evidence is scarce on such associations in China. The aim of this study was to investigate whether a plant-based diet is related to a lower risk of type 2 diabetes among Chinese adults. MATERIALS AND METHODS: A total of 37,985 participants were enrolled from the Henan Rural Cohort Study. An overall plant-based diet index (PDI) was created by assigning positive and reverse scores to 12 commonly consumed food groups. Multivariate logistic regression models and restricted cubic spline analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: After multivariable adjustment, the risk of type 2 diabetes was inversely associated with the PDI (extreme-quartile OR = 0.88, 95% CI: 0.79-0.98; P = 0.027), the risk associated with a 1 standard deviation (SD) increase in PDI was 4% lower (95% CI, 0.93-1.00; P trend  = 0.043) for type 2 diabetes. Moreover, the odds of type 2 diabetes was decreased with an increment of PDI after fitting restricted cubic splines (P trend  < 0.01). CONCLUSIONS: Among Chinese populations, diets higher in plant foods and lower in animal foods were associated with a reduced risk of type 2 diabetes.

A Facile Strategy for Immobilizing GOD and HRP onto Pollen Grain and Its Application to Visual Detection of Glucose.

Pollen grain was explored as a new carrier for enzyme immobilization. After being modified with boric acid-functionalized titania, the pollen grain was able to covalently immobilize glycosylated enzymes by boronate affinity interaction under very mild experimental conditions (e.g., pH 7.0, ambient temperature and free of organic solvent). The glucose oxidase and horse radish peroxidase-immobilized pollen grain became a bienzyme system. The pollen grain also worked as an indicator of the cascade reaction by changing its color. A rapid, simple and cost-effective approach for the visual detection of glucose was then developed. When the glucose concentration exceeded 0.5 mM, the color change was observable by the naked eye. The assay of glucose in body fluid samples exhibited its great potential for practical application.

Consumption of Dairy Products in Relation to Type 2 Diabetes Mellitus in Chinese People: The Henan Rural Cohort Study and an Updated Meta-Analysis.

Recent studies on whether dairy consumption is associated with type 2 diabetes mellitus (T2DM) have yielded inconsistent results, so we explored the relationship between dairy consumption and T2DM through a large-sample, cross-sectional study and a meta-analysis. In the meta-analysis, summary relative risks (RRs) of 23 articles were compiled with a random effects model, and a restricted cubic spline regression model was used to explore whether there is a nonlinear relationship between dairy intake and T2DM risk. This cross-sectional study used baseline data from 38,735 participants of the Henan Rural Cohort study and the association between dairy consumption and T2DM was analyzed by a logistic regression model. The meta-analysis revealed a borderline negative significant association between total dairy intake and risk of T2DM, the RR and 95% confidence interval (CI) was 0.94; (0.89, 1.00), and the risk was lowest at 270 g daily dairy intake. In the cross-sectional study, there were 3654 T2DM patients and 68.3 percent of the respondents had no dairy intake. The average intake of dairy in the total population was 12 g per day. Fully adjusted analyses suggested positive associations, with an odds ratio (OR) comparing the highest with the zero intake of 1.34 (95% CI: 1.22, 1.48) for all participants, which was unaffected by sex. Dairy intake in rural areas of Henan province is low, and we found, in the context of overall low dairy intake, that a high intake was positively associated with T2DM, which is inconsistent with the meta-analysis results suggesting that dairy has marginal protective effects against T2DM.

Novel diphenyl urea derivative serves as an inhibitor on human lung cancer cell migration by disrupting EMT via Wnt/ß-catenin and PI3K/Akt signaling.

Targeted anti-tumor small molecules are considered to be promising candidates for cancer treatment. The novel diphenyl urea derivative (DUD) was synthesized by the molecular docking based on the structure optimization of Taspine (a natural product). In this study, we explored the anti-metastatic potential of DUD for NSCLC in vitro. DUD significantly suppressed A549 cell migration by reversing EMT. The inhibition was reflected on upregulation of E-cadherin and downregulation of N-cadherin, vimentin, Snail and HIF-1α. Meanwhile, DUD inhibited the ß-catenin nuclear translocation by upregulating Axin and downregulating the expression of APC, CK1 and phosphorylation of GSK3ß, and simultaneously decreasing MMP9 and MMP13 expression. Moreover, it was associated with the downregulation of the PI3K/Akt/mTOR signaling. Furthermore, we used XAV939, an ß-catenin inhibitor, to verify the mechanism of DUD. These results suggested that DUD inhibited A549 cells migration by reversing EMT via Wnt/ß-catenin and PI3K/Akt signaling. DUD might be a potential therapeutic drug candidate for NSCLC treatment.

Age at menopause, body mass index, and risk of type 2 diabetes mellitus in postmenopausal Chinese women: The Henan Rural Cohort study.

BACKGROUND AND AIM: The present study was conducted to explore the stratified and joint effects of age at menopause and body mass index (BMI) with the risk of type 2 diabetes mellitus (T2DM) in Chinese rural adults. METHODS AND RESULTS: A total of 15,406 postmenopausal Chinese women were included in this study. Multivariable logistic regression analysis was used to quantify the stratified and joint effects of age at menopause and BMI on T2DM. Overall, the mean age at menopause and BMI was 48.8 ± 4.7 years and 25.1 ± 3.6 kg/m2, respectively. In general, data suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, later menopause had a higher risk of T2DM (OR, 1.52; 95% CI, 1.16-2.01); 3) the risk of T2DM was higher only in patients with early or normal age at menopause and BMI ≥ 24, with 0R (95% CI) of (1.58, 1.28-1.94) and (1.48, 1.31-1.67), respectively. CONCLUSION: Our findings suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, a higher risk of T2DM was found only in those with later menopause; 3) women with later menopause had a higher risk of T2DM, irrespective of BMI; 4) in patients with early or normal age at menopause, a higher risk of T2DM was found only in patients with BMI ≥ 24. THE CHINESE CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-1500669(URL:http://www.chictr.org.cn/showproj.aspx?proj=11375).

Meat and fish intake and type 2 diabetes: Dose-response meta-analysis of prospective cohort studies.

AIMS: This meta-analysis aimed to quantitatively examine the possible associations between total meat, red meat, processed meat, poultry and fish intakes and type 2 diabetes (T2D). METHODS: Relevant articles were identified in PubMed, Embase and Web of Science databases using a search time up to January 2019. Generalized least-squares trend estimations and restricted cubic spline regression models were used for analysis. RESULTS: Twenty-eight articles were included in the analysis. When comparing the highest with the lowest category of meat intake, the summary relative risk of T2D was 1.33 (95% CI: 1.16-1.52) for total meat, 1.22 (95% CI: 1.16-1.28) for red meat, 1.25 (95% CI: 1.13-1.37) for processed meat, 1.00 (95% CI: 0.93-1.07) for poultry and 1.01 (95% CI: 0.93-1.10) for fish. In the dose-response analysis, each additional 100g/day of total and red meat, and 50g/day of processed meat, were found to be associated with a 36% (95% CI: 1.23-1.49), 31% (95% CI: 1.19-1.45) and 46% (95% CI: 1.26-1.69) increased risk of T2D, respectively. In addition, there was evidence of a non-linear dose-response association between processed meat and T2D (P=0.004), with the risk increasing by 30% with increasing intakes up to 30g/day. CONCLUSION: Our meta-analysis has shown a linear dose-response relationship between total meat, red meat and processed meat intakes and T2D risk. In addition, a non-linear relationship of intake of processed meat with risk of T2D was detected.

Sanguinarine disrupts the colocalization and interaction of HIF-1α with tyrosine and serine phosphorylated-STAT3 in breast cancer.

Breast cancer is one leading cause of death in females, especially triple-negative breast cancer (TNBC). Hypoxia is a key feature leading to tumour progression driven by hypoxia-inducible factor (HIF)-1α. The aim is to investigate the mechanism of HIF-1α and signal transducer and activator of transcription-3 (STAT3) interaction and discover a compound to disrupt the interaction in breast cancer cells. The regulation pattern of HIF-1α and STAT3 was analysed in hypoxic TNBC cells and patient samples. The effects of a natural alkaloid, sanguinarine, on HIF-1α and STAT3 colocalization and interaction were evaluated in vitro and mouse xenograft models. We observed strong colocalization of HIF-1α, p-STAT3-Tyr and p-STAT3-Ser in TNBC patient samples. Sanguinarine could inhibit the nuclear colocalization and interaction of HIF-1α with p-STAT3-Tyr and p-STAT3-Ser in vivo and in vitro. Our results may bring insights to the HIF-1α/STAT3 interaction in breast cancers and suggest sanguinarine as a promising candidate for HIF-α/STAT3 inhibition.

Mineralocorticoids, glucose homeostasis and type 2 diabetes mellitus: The Henan Rural Cohort study.

AIMS: We aimed to evaluate the associations of mineralocorticoids with type 2 diabetes mellitus (T2DM) and glucose homeostasis among rural Chinese adults. METHODS: A total of 2713 participants were selected from the Henan Rural Cohort study. Serum mineralocorticoids were measured by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were employed to evaluate the associations of mineralocorticoids with pre-diabetes and T2DM. Linear regression was implemented to assess the associations of aldosterone and 11-deoxycorticosterone with different markers of glucose homeostasis by different diabetes status. RESULTS: Elevated aldosterone and 11-deoxycorticosterone were associated with an increased prevalence of pre-diabetes and T2DM (P < 0.05), with a nonlinear dose-response trend, but the association between 11-deoxycorticosterone and T2DM was no statistical significance after adjustment. A 100% increase in ln-aldosterone was associated with a 0.029 mg/dl higher fasting plasma glucose (FPG) and a 1.2% higher HOMA2-IR among those with normal glucose tolerance (NGT), and related to a 0.034 mg/dl lower FPG, a 1.1% higher HbA1c and a 1.3% higher HOMA2-ß among individuals with pre-diabetes. A 100% increment in ln-11-deoxycorticosterone was associated with a 16% increase in HbA1c and a 5.6% decrease in HOMA2-ß in participants with T2DM. CONCLUSIONS: Higher aldosterone and 11-deoxycorticosterone are associated with T2DM risk and glucose homeostasis disorder among different diabetes status.

Palladium Nanoclusters Confined in MOF@COP as a Novel Nanoreactor for Catalytic Hydrogenation.

Metal-nanocluster-doped porous materials are attracting considerable research attention due to their specific catalytic performance. In this study, core-shell metal-organic frameworks@covalent organic polymer (MOF@COP) nanocomposites were formed by the covalent linking of chemically stable COP on the surface of size-selective UiO-66-NH2. Pd nanoclusters with an average diameter of ∼0.8 nm were successfully confined in UiO-66-NH2@COP, and the obtained nanoreactor, referred to as UiO-66-NH2@COP@Pd, exhibited abundant porosity, high stability, and large surface area. Notably, the UiO-66-NH2@COP@Pd nanoreactor exhibited superior catalytic activity and stability for the catalytic reduction of 4-nitrophenol and hydrogenation of other nitroarenes, demonstrating the potential of Pd-cluster-doped MOF@COP hybrid materials as candidates for efficient catalytic hydrogenation. This study may provide new avenues for the construction of MOF@COP-hybrid-material-based heterogeneous catalysts for efficient catalytic applications.

Effect of the Age at Menarche and Menopause Status Interaction on Type 2 Diabetes: The Henan Rural Cohort Study.

PURPOSE: The aims of this study were to evaluate the effect of age at menarche (AM) on type 2 diabetes mellitus (T2DM) and to assess whether the fasting plasma glucose (FPG) and homeostasis model assessment (HOMA) index responses to AM and menopause status interact in Chinese rural adults. METHODS: A cross-sectional, population-based study including 23 138 participants was performed. Logistic regression and multivariable linear regression were performed to investigate the relationship between AM and glucose status. Generalized linear model was used to calculate the interaction term of AM and menopause status on FPG and the HOMA index. Interaction plot was used to interpret the significant interaction effect. RESULTS: Women in the later menarche age group (≥18 years) had a 17.7% lower risk of T2DM (95% confidence interval [CI]: 0.712-0.951, P = .008), after adjusting for multiple variables. Further adjustment for body mass index (BMI) completely attenuated this association (odds ratio = 0.884, 95% CI: 0.764-1.024, P = .099). A significant interaction effect of AM and menopause status on T2DM (P = .004) was observed. The adverse effects of menopausal status on FPG and HOMA-2 of insulin resistance decreased with increasing menarche age, and the age ranges were limited to <18 and 9 to 19 years, respectively. CONCLUSIONS: Later menarche was associated with a lower risk of T2DM, and the association appears to be mediated by BMI. More importantly, the adverse effect of menopause status on T2DM was decreased along with increasing menarche age.