The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Inflammatory age and its impact on age-related health in older Chinese adults.

INTRODUCTION: A standardized measure for inflammaging is lacking. We introduced the inflammatory age (iAge) as a quantification method and explored its associations with age-related traits and diseases in an older Chinese cohort. METHODS: Inflammatory markers including white blood cell count (WBC), neutrophils, lymphocytes, monocytes, C-reactive protein, platelets and albumin were measured. Quantitative real-time polymerase chain reaction was used to measure telomere length. Traditional multivariable linear, partial least squares, and logistic regression were used. RESULTS: iAge was constructed based on WBC, neutrophils, monocytes and albumin, which were associated with telomere length independently. A higher iAge indicated a heavier aging-related inflammation burden. Per 1-year increase in iAge was associated with higher body mass index (ß 0.86 (95 % CI 0.67, 1.05) kg/m2), waist circumference (ß 2.37 (95 % CI 1.85, 2.90) cm), glycosylated hemoglobin A1c (ß 0.06 (95 % CI 0.02, 0.10) %), systolic blood pressure (ß 1.06 (95 % CI 0.10, 2.03) mmHg), triglycerides (ß 0.05 (95 % CI 0.01, 0.08) mmol/L), 10-year cardiovascular diseases risk (ß 0.05 (95 % CI 0.02, 0.08) %), diabetes (OR 1.22 (95 % CI 1.02, 1.46)), hypertension (OR 1.21 (95 % CI 1.04, 1.42)) and metabolic syndrome risks (OR 1.25 (95 % CI 1.04, 1.51)), and lower fasting plasma glucose (ß -0.016 (95 % CI -0.024, -0.007) mmol/L), total cholesterol (ß -0.06 (95 % CI -0.12, -0.01) mmol/L) and high-density lipoprotein cholesterol (ß -0.05 (95 % CI -0.07, -0.03) mmol/L). CONCLUSION: The newly introduced iAge, derived from inflammatory markers and telomere length, aligns with various metabolic dysfunctions and age-related disease risks, underscoring its potential ability in identifying aging-related phenotypes.

Transjugular intrahepatic portosystemic shunt: A promising therapy for recompensation in cirrhotic patients.

This is a retrospective study focused on recompensation after transjugular intrahepatic portosystemic shunt (TIPS) procedure. The authors confirmed TIPS could be a treatment for recompensation of patients with cirrhosis according to Baveno VII. The paper identified age and post-TIPS portal pressure gradient as independent predictors of recompensation in patients with decompensated cirrhosis after TIPS. These results need to be validated in a larger prospective cohort.

Skeletal muscle index based on CT at the 12th thoracic spine level can predict osteoporosis and fracture risk: a propensity score-matched cohort study.

Background: Multiple studies have shown that skeletal muscle index (SMI) measured on abdominal computed tomography (CT) is strongly associated with bone mineral density (BMD) and fracture risk as estimated by the fracture risk assessment tool (FRAX). Although some studies have reported that SMI at the level of the 12th thoracic vertebra (T12) measured on chest CT images can be used to diagnose sarcopenia, it is regrettable that no studies have investigated the relationship between SMI at T12 level and BMD or fracture risk. Therefore, we further investigated the relationship between SMI at T12 level and FRAX-estimated BMD and fracture risk in this study. Methods: A total of 349 subjects were included in this study. After 1∶1 propensity score matching (PSM) on height, weight, hypertension, diabetes, hyperlipidemia, hyperuricemia, body mass index (BMI), age, and gender, 162 subjects were finally included. The SMI, BMD, and FRAX score of the 162 participants were obtained. The correlation between SMI and BMD, as well as SMI and FRAX, was assessed using Spearman rank correlation. Additionally, the effectiveness of each index in predicting osteoporosis was evaluated through the receiver operating characteristic (ROC) curve analysis. Results: The BMD of the lumbar spine (L1-4) demonstrated a strong correlation with SMI (r = 0.416, p < 0.001), while the BMD of the femoral neck (FN) also exhibited a correlation with SMI (r = 0.307, p < 0.001). SMI was significantly correlated with FRAX, both without and with BMD at the FN, for major osteoporotic fractures (r = -0.416, p < 0.001, and r = -0.431, p < 0.001, respectively) and hip fractures (r = -0.357, p < 0.001, and r = -0.311, p < 0.001, respectively). Moreover, the SMI of the non-osteoporosis group was significantly higher than that of the osteoporosis group (p < 0.001). SMI effectively predicts osteoporosis, with an area under the curve of 0.834 (95% confidence interval 0.771-0.897, p < 0.001). Conclusion: SMI based on CT images of the 12th thoracic vertebrae can effectively diagnose osteoporosis and predict fracture risk. Therefore, SMI can make secondary use of chest CT to screen people who are prone to osteoporosis and fracture, and carry out timely medical intervention.

Associations of cognitive impairment and longitudinal change in cognitive function with the risk of fatal stroke in middle-aged to older Chinese.

It is unclear whether cognitive impairment and the longitudinal change in cognition are associated with the risk of fatal stroke in aging populations. Based on the Guangzhou Biobank Cohort Study data a sum of 26,064 participants at baseline and all deaths caused by stroke in a mean follow-up of 14.3 years (standard deviation = 3.2) were included, and the Cox proportional hazard regression was used in this prospective cohort study. Cognitive impairment was respectively associated with an increased risk of fatal strokes (the adjusted hazard ratio (aHR) = 1.38, 95% CI1.16-1.64, P < 0.001) and fatal ischaemic stroke (aHR = 1.39, 95% CI1.10-1.77, P = 0.007), compared to median cognition; the Delayed Word Recall Test (DWRT) score was associated with a decreasing trend for the risk of fatal strokes in a restricted cubic spline analysis; the longitudinal DWRT score decline was associated with the increased risks of fatal strokes (aHR = 1.42, 95% CI 1.11-1.82, P = 0.006) and fatal haemorrhagic stroke (aHR = 1.75, 95% CI 1.10-2.78, P = 0.02), compared to the longitudinal DWRT score rise. In summary, cognitive impairment and the longitudinal decline in DWRT scores were associated with the increased risk of fatal strokes; early screening of cognitive function should be conducive to predictive intervention in fatal stroke among relatively healthy middle-aged to older populations.

Ago2/CAV1 interaction potentiates metastasis via controlling Ago2 localization and miRNA action.

Ago2 differentially regulates oncogenic and tumor-suppressive miRNAs in cancer cells. This discrepancy suggests a secondary event regulating Ago2/miRNA action in a context-dependent manner. We show here that a positive charge of Ago2 K212, that is preserved by SIR2-mediated Ago2 deacetylation in cancer cells, is responsible for the direct interaction between Ago2 and Caveolin-1 (CAV1). Through this interaction, CAV1 sequesters Ago2 on the plasma membranes and regulates miRNA-mediated translational repression in a compartment-dependent manner. Ago2/CAV1 interaction plays a role in miRNA-mediated mRNA suppression and in miRNA release via extracellular vesicles (EVs) from tumors into the circulation, which can be used as a biomarker of tumor progression. Increased Ago2/CAV1 interaction with tumor progression promotes aggressive cancer behaviors, including metastasis. Ago2/CAV1 interaction acts as a secondary event in miRNA-mediated suppression and increases the complexity of miRNA actions in cancer.

Physician Versus Large Language Model Chatbot Responses to Web-Based Questions From Autistic Patients in Chinese: Cross-Sectional Comparative Analysis.

BACKGROUND: There is a dearth of feasibility assessments regarding using large language models (LLMs) for responding to inquiries from autistic patients within a Chinese-language context. Despite Chinese being one of the most widely spoken languages globally, the predominant research focus on applying these models in the medical field has been on English-speaking populations. OBJECTIVE: This study aims to assess the effectiveness of LLM chatbots, specifically ChatGPT-4 (OpenAI) and ERNIE Bot (version 2.2.3; Baidu, Inc), one of the most advanced LLMs in China, in addressing inquiries from autistic individuals in a Chinese setting. METHODS: For this study, we gathered data from DXY-a widely acknowledged, web-based, medical consultation platform in China with a user base of over 100 million individuals. A total of 100 patient consultation samples were rigorously selected from January 2018 to August 2023, amounting to 239 questions extracted from publicly available autism-related documents on the platform. To maintain objectivity, both the original questions and responses were anonymized and randomized. An evaluation team of 3 chief physicians assessed the responses across 4 dimensions: relevance, accuracy, usefulness, and empathy. The team completed 717 evaluations. The team initially identified the best response and then used a Likert scale with 5 response categories to gauge the responses, each representing a distinct level of quality. Finally, we compared the responses collected from different sources. RESULTS: Among the 717 evaluations conducted, 46.86% (95% CI 43.21%-50.51%) of assessors displayed varying preferences for responses from physicians, with 34.87% (95% CI 31.38%-38.36%) of assessors favoring ChatGPT and 18.27% (95% CI 15.44%-21.10%) of assessors favoring ERNIE Bot. The average relevance scores for physicians, ChatGPT, and ERNIE Bot were 3.75 (95% CI 3.69-3.82), 3.69 (95% CI 3.63-3.74), and 3.41 (95% CI 3.35-3.46), respectively. Physicians (3.66, 95% CI 3.60-3.73) and ChatGPT (3.73, 95% CI 3.69-3.77) demonstrated higher accuracy ratings compared to ERNIE Bot (3.52, 95% CI 3.47-3.57). In terms of usefulness scores, physicians (3.54, 95% CI 3.47-3.62) received higher ratings than ChatGPT (3.40, 95% CI 3.34-3.47) and ERNIE Bot (3.05, 95% CI 2.99-3.12). Finally, concerning the empathy dimension, ChatGPT (3.64, 95% CI 3.57-3.71) outperformed physicians (3.13, 95% CI 3.04-3.21) and ERNIE Bot (3.11, 95% CI 3.04-3.18). CONCLUSIONS: In this cross-sectional study, physicians' responses exhibited superiority in the present Chinese-language context. Nonetheless, LLMs can provide valuable medical guidance to autistic patients and may even surpass physicians in demonstrating empathy. However, it is crucial to acknowledge that further optimization and research are imperative prerequisites before the effective integration of LLMs in clinical settings across diverse linguistic environments can be realized. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300074655; https://www.chictr.org.cn/bin/project/edit?pid=199432.

Association of Cantonese dietary patterns with mortality risk in older Chinese: a 16-year follow-up of a Guangzhou Biobank cohort study.

Background: Evidence about the associations between Cantonese dietary patterns and mortality is scarce. We examined the prospective association of the dietary pattern with all-cause, cancer and cardiovascular disease (CVD) mortality in older Chinese. Methods: We included 19 598 participants of a Guangzhou Biobank cohort study aged 50+ years, who were recruited from 2003 to 2006 and followed up until July, 2022. The diet was assessed by using a 300-item validated food frequency questionnaire. The food items were collapsed into 27 food groups. Factor analysis (FA) was used to identify dietary patterns. Multivariable Cox regression produced hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: During 305 410 person-years, 4966 deaths including 1971 CVD, 1565 cancer and 1436 other-causes occurred. Four dietary patterns were identified by FA. No association of the vegetable-based dietary pattern with all-cause, CVD and cancer mortality was found. Compared with the lowest quartile of the healthy Cantonese dietary pattern score, the highest quartile showed lower risks of all-cause (HR 0.86, 95% CI 0.80-0.94) and CVD mortality (HR 0.84, 95% CI 0.72-0.97). The highest quartile of the nut and fruit dietary pattern showed lower risks of all-cause (HR 0.92, 95% CI 0.85-0.99) and CVD mortality (HR 0.82, 95% CI 0.72-0.93), while the unhealthy western dietary pattern was associated with a higher risk of all-cause (HR 1.10, 95% CI 1.01-1.19) and cerebrovascular disease mortality (HR 1.28, 95% CI 1.03-1.58). Conclusion: We have first identified four dietary patterns based on the Cantonese cuisine and found that healthy Cantonese and nut and fruit dietary patterns were associated with lower risks of all-cause and CVD mortality, whereas the unhealthy western dietary pattern was associated with a higher risk of all-cause and cerebrovascular disease mortality.

Associations of soy product intake with all-cause, cardiovascular disease and cancer mortality: Guangzhou Biobank Cohort Study and updated meta-analyses.

PURPOSE: We examined the associations of soy product intake with all-cause, cardiovascular disease (CVD), and cancer mortality and mediations through CVD risk factors based on the Guangzhou Biobank Cohort Study (GBCS), and conducted updated meta-analyses. METHODS: A total of 29,825 participants aged 50 + years were included. Causes of death were identified through record linkage. Soy product intake was assessed by food frequency questionnaire. Cox proportional hazards regression was used to analyze the associations between soy product intake and mortality, yielding hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses with CVD risk factors as mediators, and updated meta-analyses were conducted. RESULTS: During 454,689 person-years of follow-up, 6899 deaths occurred, including 2694 CVD and 2236 cancer. Participants who consumed soy product of 1-6 portions/week, versus no consumption, had significantly lower risks of all-cause and CVD mortality (adjusted HR (95% CI) 0.91 (0.86, 0.97) and 0.87 (0.79, 0.96), respectively). In participants who consumed soy product of ≥ 7 portions/week, the association of higher intake with lower CVD mortality was modestly mediated by total cholesterol (4.2%, 95% CI 1.0-16.6%). Updated meta-analyses showed that the highest level of soy product intake, versus the lowest, was associated with lower risks of all-cause and CVD mortality (pooled HR (95% CI) 0.92 (0.88, 0.96) and 0.92 (0.87, 0.98), respectively). CONCLUSION: Moderate and high soy product intake were associated with lower risks of all-cause and CVD mortality. Our findings provide support for current dietary guidelines recommending moderate soy product intake, and contribute additional evidence regarding the potential protective effects of high soy product intake.

Ultrasensitive detection of zearalenone based on electrochemiluminescent immunoassay with Zr-MOF nanoplates and Au@MoS2 nanoflowers.

In this work, an effective competitive-type electrochemiluminescence (ECL) immunosensor was constructed for zearalenone determination by using Zr-MOF nanoplates as the ECL luminophore and Au@MoS2 nanoflowers as the substrate material. Zr-MOF have an ultra-thin sheet-like structure that accelerates the transfer of electrons, ions and co-reactant intermediates, which exhibited strong and stable anodic luminescence. The three-dimensional Au@MoS2 nanoflowers would form a thin film modification layer on the glassy carbon electrode (GCE). And its good electrical conductivity and higher specific surface area utilization further improving the sensitivity of the ECL immunosensor. Under the optimized conditions, the proposed immunosensor exhibited satisfactory stability, sensitivity and accuracy, and its ECL signal was proportional to the logarithm of ZEN concentration (0.0001-100 ng/mL) and the limit of detection (LOD) was 0.034 pg/mL. In addition, the results of recovery experiment acquired for wheat flour and pig urine samples further proved the feasibility of the immunosensor for the detection of real samples, indicating its potential for ultrasensitive detection of ZEN.

Association of Testosterone and Sex Hormone-Binding Globulin With All-Cause and Cardiovascular Disease Mortality in Older Chinese Men.

BACKGROUND: The associations of high and low testosterone with all-cause and cardiovascular disease (CVD) mortality risk in men are conflicting. Our objective was to examine associations of total testosterone, free testosterone, bioavailable testosterone, and sex hormone-binding globulin (SHBG) with all-cause and CVD mortality in older Chinese men. METHODS: Total testosterone and SHBG were assayed, and free testosterone and bioavailable testosterone were calculated using Vermeulen formula. Cox proportional hazards regression was used to assess the associations with risks of all-cause and CVD mortality, giving hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Of 3 948 men aged 50+ years, 949 deaths (312 CVD) occurred during an average 10.5-year follow-up. After multivariable adjustments, the highest, versus the third, quartile of total testosterone and free testosterone were associated with higher all-cause mortality risk (1.17 [0.97-1.41] and 1.45 [1.20-1.74], respectively), whereas free testosterone was associated with higher CVD mortality risk (1.88 [1.33-2.66]). Similar positive associations were found for bioavailable testosterone and all-cause mortality risk (1.27 [1.05-1.54]). Lower SHBG (quartile 1 vs quartile 3) was associated with higher all-cause and CVD mortality risk (1.25 [1.04-1.52] and 1.28 [1.08-1.52], respectively). Consistent associations were observed in relatively healthy men and men excluded death during the first year. CONCLUSIONS: Higher total testosterone, free testosterone, and bioavailable testosterone were associated with higher all-cause mortality in older men, higher free testosterone was associated with higher CVD mortality whilst lower SHBG was associated with higher all-cause and CVD mortality. Clarification and confirmation of causality require further mechanistic studies.

Exploring Nutrient Profiles, Phytochemical Composition, and the Antiproliferative Activity of Ganoderma lucidum and Ganoderma leucocontextum: A Comprehensive Comparative Study.

Ganoderma, often hailed as a holistic "health package", comprises an array of nutritional components and active compounds, contributing to its esteemed status in the realm of healthy foods. In this study, a comprehensive analysis was performed to elucidate the diverse nutritional profiles, bioactive components, and antiproliferative activities between two Ganoderma species: G. lucidum (GLU) and G. leucocontextum (GLE). The results showed that GLE possessed a higher level of nutritional constituents, except for dietary fiber. Fatty acid analysis revealed comparable profiles rich in unsaturated fatty acids for both species. The ethanol extract of GLU and GLE exhibited potent antioxidant capabilities and remarkable inhibition of tumor cell proliferation via apoptosis induction, with greater potency in GLE. The heightened triterpene levels in GLE potentially contribute to its augmented antitumoral effects. The exploration emphasized the significance of comprehending the varied chemical compositions of Ganoderma species, providing insights into their potential health benefits applications in the food and pharmaceutical industries.

Association of adverse childhood experiences with anemia in older Chinese: Guangzhou Biobank Cohort Study.

To examine the association of adverse childhood experiences (ACEs) with anemia among older people. 24,116 participants aged 50 years or above were recruited. Multivariable linear and logistic regression was used to assess the associations of self-reported ACEs number with hemoglobin concentrations (g/dL) and presence of anemia. Older individuals with two or more ACEs, versus no ACEs, showed lower hemoglobin concentrations (ß = - 0.08 g/dL, 95% confidence intervals (CI) - 0.12 to - 0.03) and higher odds of anemia (odds ratio = 1.26, 95% CI 1.01-1.59). A more pronounced association between ACEs and anemia in the lower education group was found, while the association became non-significant in those with higher education (P for ACEs-education interaction = 0.02). ACEs was associated with anemia in older people, and the association was stronger in those with lower education, highlighting the significance of early-life psychological stressors assessment and consideration of education background in geriatric care.

Neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in elderly patients with stage III-IVa nasopharyngeal carcinoma: A real-world study based on medical comorbidities.

PURPOSE: To evaluate the outcomes and toxicities of adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) in elderly (≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (LANPC, stage III-IVa). METHODS AND MATERIALS: Using an NPC-specific database, 245 elderly patients with stage III-IVa NPC, receiving CCRT +/- NAC, and an Adult Co-morbidity Evaluation 27 (ACE-27) score <2 were included. Recursive partitioning analysis (RPA) based on TNM stage and Epstein-Barr virus (EBV) DNA were applied for risk stratification. The primary end point was disease-free survival (DFS). RESULTS: Two risk groups were generated by the RPA model. In the high-risk group (EBV DNA < 4000 copy/ml with stage IVa & EBV DNA ≥4000 copy/ml with stage III-IVa), patients treated with NAC plus CCRT achieved improved 5-year DFS rates compared to those who received CCRT alone (56.9% vs. 29.4%; p = 0.003). But we failed to observe the survival benefit of additional NAC in the low-risk group (EBV DNA <4000 copy/ml with stage III). The most common severe acute toxic effects were leucopenia (46.8% vs. 24.4%) and neutropenia (43.7% vs. 20.2%) in the NAC plus CCRT group versus CCRT group with statistically significant differences. CONCLUSIONS: The addition of NAC to CCRT was associated with better DFS for the high-risk group of elderly LANPC patients with ACE-27 score <2. However, the survival benefit of additional NAC was not observed in low-risk patients.

Association of Measures of Glucose Metabolism with Colorectal Cancer Risk in Older Chinese: A 13-Year Follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis.

BACKGRUOUND: Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis. METHODS: Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk. RESULTS: During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies. CONCLUSION: Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Genome-wide identification and expression analysis of NIN-like protein (NLP) genes: Exploring their potential roles in nitrate response in tea plant (Camellia sinensis).

NIN-like proteins (NLPs) are evolutionarily conserved transcription factors that are unique to plants and play a pivotal role in responses to nitrate uptake and assimilation. However, a comprehensive analysis of NLP members in tea plants is lacking. The present study performed a genome-wide analysis and identified 33 NLP gene family members of Camellia sinensis that were distributed unequally across 5 chromosomes. Subcellular localisation predictions revealed that all CsNLP proteins were localised in the nucleus. Conservative domain analysis revealed that all of these proteins contained conserved RWP-RK and PB1 domains. Phylogenetic analysis grouped the CsNLP gene family into four clusters. The promoter regions of CsNLPs harboured cis-acting elements associated with plant hormones and abiotic stress responses. Expression profile analysis demonstrated that CsNLP8 was significantly upregulated in roots under nitrate stress conditions. Subcellular localisation analysis found CsNLP8 localised to the nucleus. Dual-luciferase reporter assay demonstrated that CsNLP8 positively regulated the expression of a nitrate transporter gene (CsNRT2.2). These findings provide a comprehensive characterisation of NLP genes in Camellia sinensis and offer insights into the biological function of CsNLP8 in regulating the response to nitrate-induced stress.

Association of insulin resistance and glycemic measures with major abnormal electrocardiogram in older Chinese: Cross-sectional analysis based on the Guangzhou Biobank Cohort study.

AIMS: To examine whether insulin resistance (IR) and glycemic measures were associated with major abnormal electrocardiogram (MA-ECG) and its specific abnormalities in the general population. METHODS: Twelve-lead ECG measurements were performed on 21,720 participants without cardiovascular disease (5,918 men) from the Guangzhou Biobank Cohort Study. The participants were aged 50 years or above (mean age 61.6, standard deviation 7.1 years). Logistic regression was used to assess the associations of IR and glycemic measures with MA-ECG and specific abnormalities. RESULTS: Ln-fasting insulin was significantly associated with MA-ECG and ST-T abnormalities (adjusted odds ratio = 1.52, 95 % confidence interval = 1.15-2.02 and 1.83, 1.37-2.45, respectively, for per standard deviation), which were stronger than those of TyG index with MA-ECG (1.08, 1.04-1.13) and ST-T abnormalities (1.16, 1.11-1.22). Ln-fasting insulin had association with Q wave abnormalities (3.19, 1.52-6.67). The association of TyG index with prolonged QTc varied by sex and obesity (P for interaction ≤ 0.01). Participants with diabetes had stronger associations of ln-fasting plasma glucose with ECG abnormalities than those without. CONCLUSIONS: IR and glycemic measures were associated with MA-ECG, ischemia and prolonged QTc in older Chinese, especially in women, those with obesity, and those with diabetes. These findings underscore the importance of regular evaluations for these groups.

Associations Between Sleep Traits and Social Isolation: Observational and Bidirectional Mendelian Randomization Study.

Social isolation has been found associated with multiple sleep traits in conventional observational studies. However, whether this association is causal and if so, its direction is uncertain. We analyzed the association between social isolation and multiple sleep traits in 30 430 participants from the Guangzhou Biobank Cohort Study. In bidirectional Mendelian randomization, we used 6, 17, and 11 single nucleotide polymorphisms associated with attendance at sports club/gym, religious group, and pub/social club from the UK Biobank (n = 452 302), respectively, and 152 single nucleotide polymorphisms associated with insomnia from the combination of UK Biobank and 23andme (n = 1 331 010). Observationally in the Guangzhou Biobank Cohort Study, insomnia (yes/no) (beta = 0.12, 95% confidence interval (CI) 0.10-0.16) and poor sleep quality (yes/no) (beta = 0.12, CI: 0.08-0.15), but not sleep duration and chronotype, were associated with a higher social isolation score (severe social isolation). In bidirectional MR, genetically predicted insomnia decreases the odds of attendance at sports club/gym (beta = 0.98, CI: 0.98-0.99) and religious groups (beta = 0.99, CI: 0.98-0.99), but not pub/social club. However, these 3 types of social activity were not associated with insomnia. Our results support the causal effects of insomnia on social activity. Further clinical investigations into the utility of insomnia treatment in alleviating social isolation are needed.

Insights into starch-based gels: Selection, fabrication, and application.

Starch a natural polymer, has made significant advancements in recent decades, offering superior performance and versatility compared to synthetic materials. This review discusses up-to-date diverse applications of starch gels, their fabrication techniques, and their advantages over synthetic materials. Starch gels renewability, biocompatibility, biodegradability, scalability, and affordability make them attractive. Also, advanced theoretical foundations and emerging industrial technologies could further expand their scope and functions inspiring new applications.

[Effect of miR-22 Targeting FMNL2 on Cell Migration and Apoptosis in Childhood Acute Myeloid Leukemia].

OBJECTIVE: To investigate the effect of miR-22 targeting formin-like protein 2 (FMNL2) on the migration and apoptosis of childhood acute myeloid leukemia (AML) cells. METHOD: Peripheral blood samples from 11 children with AML, 10 children with immune thrombocytopenia, human AML cell lines TF-1a, HL-60, THP-1 and human bone marrow stromal cells HS-5 were used as the research objects. UniCel DxH 800 automatic hematology analyzer detected platelet count, hemoglobin, and white blood cell count in peripheral blood samples, and RT-qPCR detected miR-22 expression in peripheral blood samples and AML cells. HL-60 cells were transfected with LipofectamineTM 2000 kit, the experiments were divided into seven groups: blank (no cells transfected), miR-NC, miR-22 mimics, si-NC, si-FMNL2 , miR-22 mimics+OE-NC and miR-22 mimics+OE-FMNL2 . RT-qPCR was used to detect the expression of miR-22 in each group. Transwell was used to detect cell migration. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter gene detection experiments verified the targeting relationship between miR-22 and FMNL2 . Western blot was used to detect the expression of FMNL2 protein. RESULTS: Compared with the control group, the number of leukocytes in the peripheral blood of children with AML was significantly increased (P <0.001), while the concentration of hemoglobin and the number of platelets were significantly decreased P <0.001). The expression level of miR-22 in peripheral blood of children with AML was significantly lower than that in control group (P <0.001). Compared with HS-5 cells, the expression levels of miR-22 in TF-1a, HL-60, and THP-1 cells were significantly decreased (P <0.05), and in HL-60 cells was the lowest. Therefore, HL-60 cells were selected for subsequent experiments. Up-regulation of miR-22 or silencing of FMNL2 could reduce the number of migrating cells and increase apoptosis rate (P <0.05). MiR-22 targeted and negatively regulated the expression of FMNL2 . FMNL2 overexpression reversed the effects of up-regulated miR-22 on migration and apoptosis of HL-60 cells. CONCLUSION: MiR-22 can inhibit the migration and promote apoptosis of HL-60 cells by down regulating the expression of FMNL2 .