Enhancement of the Tumor Suppression Effect of High-dose Radiation by Low-dose Pre-radiation Through Inhibition of DNA Damage Repair and Increased Pyroptosis.

Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.

Association between perioperative red blood cell transfusions and postoperative venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Whether perioperative red blood cell transfusions increases the risk of postoperative venous thromboembolism is controversial and uncertain.We aims to explore the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism by conducting a meta-analysis. OBJECTIVE: To conduct a meta-analysis to systematically evaluate the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism. METHODS: PubMed, Embase, Cochrane, and Web of Science databases were searched to identify studies examining the relationship between perioperative red blood cell transfusions and the risk of postoperative venous thromboembolism. The databases were searched from establishment to August 2023.Two researchers independently screened literature and extracted data according to inclusion and exclusion criteria. Newcastle-ottawa Scale was used for quality assessment. Meta-analysis of data was performed using RevMan 5.4 software. RESULTS: A total of 15 studies involving 1,880,990 patients were included in this study.Meta-analysis showed that perioperative red blood cell transfusions increased the risk of postoperative venous thromboembolism [OR = 1.61, 95%CI (1.37, 1.89), P < 0.001]. Subgroup analyses showed that the transfusion dose,transfusion timing,study population and follow-up time were closely related to the risk of postoperative venous thromboembolism. CONCLUSIONS: In summary, this meta-analysis demonstrated a significant positive association between perioperative red blood cell transfusions and postoperative venous thromboembolism.Healthcare professionals should pay attention to the influence of blood transfusions on postoperative venous thromboembolism, strengthen management and prevention.

Inhibition of macrophage MAPK/NF-κB pathway and Th2 axis by mangiferin ameliorates MC903-induced atopic dermatitis.

Available online Atopic dermatitis (AD) is a chronic, persistent inflammatory skin disease characterized by eczema-like lesions and itching. Although topical steroids have been reported for treating AD, they are associated with adverse effects. Thus, safer medications are needed for those who cannot tolerate these agents for long periods. Mangiferin (MAN) is a flavonoid widely found in many herbs, with significant anti-inflammatory and immunomodulatory activities. However, the potential modulatory effects and mechanisms of MAN in treating Th2 inflammation in AD are unknown. In the present study, we reported that MAN could reduce inflammatory cell infiltration and scratching at the lesion site by decreasing MC903-induced levels of Th2-type cytokines, Histamine, thymic stromal lymphopoietin, Leukotriene B4, and immunoglobulin E. The mechanism may be related to reductions in MAPK and NF-κB-associated protein phosphorylation by macrophages. The results suggested that MAN may be a promising therapeutic agent for AD.

A blood-based multi-omic landscape for the molecular characterization of kidney stone disease.

Kidney stone disease (KSD, also named renal calculi, nephrolithiasis, or urolithiasis) is a common urological disease entailing the formation of minerals and salts that form inside the urinary tract, frequently caused by diabetes, high blood pressure, hypertension, and monogenetic components in most patients. 10% of adults worldwide are affected by KSD, which continues to be highly prevalent and with increasing incidence. For the identification of novel therapeutic targets in KSD, we adopted high-throughput sequencing and mass spectrometry (MS) techniques in this study and carried out an integrative analysis of exosome proteomic data and DNA methylation data from blood samples of normal and KSD individuals. Our research delineated the profiling of exosomal proteins and DNA methylation in both healthy individuals and those afflicted with KSD, finding that the overexpressed proteins and the demethylated genes in KSD samples are associated with immune responses. The consistency of the results in proteomics and epigenetics supports the feasibility of the comprehensive strategy. Our insights into the molecular landscape of KSD pave the way for a deeper understanding of its pathogenic mechanism, providing an opportunity for more precise diagnosis and targeted treatment strategies for KSD.

Ultrasensitive CCL2 Detection in Urine for Diabetic Nephropathy Diagnosis Using a WS2-Based Plasmonic Biosensor.

The accurate diagnosis of diabetic nephropathy relies on achieving ultrasensitive biosensing for biomarker detection. However, existing biosensors face challenges such as poor sensitivity, complexity, time-consuming procedures, and high assay costs. To address these limitations, we report a WS2-based plasmonic biosensor for the ultrasensitive detection of biomarker candidates in clinical human urine samples associated with diabetic nephropathy. Leveraging plasmonic-based electrochemical impedance microscopy (P-EIM) imaging, we observed a remarkable charge sensitivity in monolayer WS2 single crystals. Our biosensor exhibits an exceptionally low detection limit (0.201 ag/mL) and remarkable selectivity in detecting CC chemokine ligand 2 (CCL2) protein biomarkers, outperforming conventional techniques such as ELISA. This work represents a breakthrough in traditional protein sensors, providing a direction and materials foundation for developing ultrasensitive sensors tailored to clinical applications for biomarker sensing.

Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation.

Objective: In the present study, we investigated the impact of left atrial appendage closure (LAAC) following catheter ablation (CA) on the left atrial structure and functioning of patients with paroxysmal atrial fibrillation (AF). Methods: Patients with paroxysmal AF were enrolled in this single-center prospective cohort study between April 2015 and July 2021; 353 patients received CA alone, while 93 patients received CA in combination with Watchman LAAC. We used age, gender, CHA2DS2-VASc, and HAS-BLED scores as well as other demographic variables to perform propensity score matching. Patients with paroxysmal AF were randomly assigned to the CA combined with Watchman LAAC group (combined treatment group) and the simple CA group, with 89 patients in each group. The left atrial structure, reserve, ventricular diastole, and pump functions and their changes in patients were assessed using routine Doppler echocardiography and 2D speckle tracking echocardiography over the course of a 1-year follow-up. Results: At 1-week follow-up, the reserve, ventricular diastole, and pump functions of the left atrium (LA) increased in both groups; these functions were gradually restored at the 1- to 3-month follow-up; they were close to or returned to their pre-operative levels at the 3-month follow-up; and no significant differences were found compared with the pre-operative levels at the 12-month follow-up. In the first 3 months, the reserve (Ƹ, SRs) and pump functions (SRa) in the combined treatment group decreased significantly when compared with the simple CA group, and the differences were statistically significant. Conclusion: Patients with paroxysmal AF may experience a short term, partial effect of LAAC on LA reserve and pump functions, which are gradually restored and the effect disappears by 12 months.

Investigating the Immunogenic Cell Death-Dependent Subtypes and Prognostic Signature of Triple-Negative Breast Cancer.

Recently, immunotherapy has emerged as a promising and effective method for treating triple-negative breast cancer (TNBC). However, challenges still persist. Immunogenic cell death (ICD) is considered a prospective treatment and potential combinational treatment strategy as it induces an anti-tumor immune response by presenting the antigenic epitopes of dead cells. Nevertheless, the ICD process in TNBC and its impact on disease progression and the response to immunotherapy are not well understood. In this study, we observed dysregulation of the ICD process and verified the altered expression of prognostic ICD genes in TNBC through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To investigate the potential role of the ICD process in TNBC progression, we determined the ICD-dependent subtypes, and two were identified. Analysis of their distinct tumor immune microenvironment (TIME) and cancer hallmark features revealed that Cluster 1 and 2 corresponded to the immune "cold" and "hot" phenotypes, respectively. In addition, we constructed the prognostic signature ICD score of TNBC patients and demonstrated its clinical independence and generalizability. The ICD score could also serve as a potential biomarker for immune checkpoint blockade and may aid in the identification of targeted effective agents for individualized clinical strategies. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00133-x.

CdgB Regulates Morphological Differentiation and Toyocamycin Production in Streptomyces diastatochromogenes 1628.

Bis (3',5')-cyclic diguanylic acid (c-di-GMP) is a ubiquitous second messenger that controls several metabolic pathways in bacteria. In Streptomyces, c-di-GMP is associated with morphological differentiation, which is related to secondary metabolite production. In this study, we identified and characterized a diguanylate cyclase (DGC), CdgB, from Streptomyces diastatochromogenes 1628, which may be involved in c-di-GMP synthesis, through genetic and biochemical analyses. To further investigate the role of CdgB, the cdgB-deleted mutant strain Δ-cdgB and the cdgB-overexpressing mutant strain O-cdgB were constructed by genetic engineering. A phenotypic analysis revealed that the O-cdgB colonies exhibited reduced mycelium formation, whereas the Δ-cdgB colonies displayed wrinkled surfaces and shriveled mycelia. Notably, O-cdgB demonstrated a significant increase in the toyocamycin (TM) yield by 47.3%, from 253 to 374 mg/L, within 10 days. This increase was accompanied by a 6.7% elevation in the intracellular concentration of c-di-GMP and a higher transcriptional level of the toy cluster within four days. Conversely, Δ-cdgB showed a lower c-di-GMP concentration (reduced by 6.2%) in vivo and a reduced toyocamycin production (decreased by 28.9%, from 253 to 180 mg/L) after 10 days. In addition, S. diastatochromogenes 1628 exhibited a slightly higher inhibitory effect against Fusarium oxysporum f. sp. cucumerinum and Rhizoctonia solani compared to Δ-cdgB, but a lower inhibition rate than that of O-cdgB. The results imply that CdgB provides a foundational function for metabolism and the activation of secondary metabolism in S. diastatochromogenes 1628.

Effects of Exercise on Gut Microbiota of Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: The equilibrium between gut microbiota (GM) and the host plays a pivotal role in maintaining overall health, influencing various physiological and metabolic functions. Emerging research suggests that exercise modulates the abundance and functionality of gut bacteria, yet the comprehensive effects on GM diversity remain to be synthesized. OBJECTIVES AND DESIGN: The study aims to quantitatively examine the effect of exercise on the diversity of gut microbiota of adults using a systemic review and meta-analysis approach. METHODS: PubMed, Ebsco, Embase, Web of Science, Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, and Wanfang Data were searched from their inception to September 2023. Exercise intervention studies with a control group that describe and compare the composition of GM in adults, using 16S rRNA gene sequencing, were included in this meta-analysis. RESULTS: A total of 25 studies were included in this meta-analysis with a total of 1044 participants. Based on a fixed-effects model [Chi2 = 29.40, df = 20 (p = 0.08); I2 = 32%], the pooled analysis showed that compared with the control group, exercise intervention can significantly increase the alpha diversity of adult GM, using the Shannon index as an example [WMD = 0.05, 95% CI (0.00, 0.09); Z = 1.99 (p = 0.05)]. In addition, exercise interventions were found to significantly alter GM, notably decreasing Bacteroidetes and increasing Firmicutes, indicating a shift in the Firmicutes/Bacteroidetes ratio. The subgroup analysis indicates that females and older adults appear to exhibit more significant changes in the Shannon Index and observed OTUs. CONCLUSIONS: Exercise may be a promising way to improve GM in adults. In particular, the Shannon index was significantly increased after exercise. Distinct responses in GM diversity to exercise interventions based on gender and age implicated that more research was needed.

Mapping network connection and direction among symptoms of depression and anxiety in patients with chronic gastritis.

Regarding neurophysiological and developmental findings, anxiety and depression are usual comorbidities of gastritis patients. However, research related to anxiety and depression among chronic gastritis patients was conducted on the disease level while ignoring symptoms. Hence, we rendered the network approach to reveal the symptoms of anxiety and depression among chronic gastritis patients. Three hundred and sixty-nine chronic gastritis patients (female = 139, Mage = 55.87 years) were asked to complete the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Three symptom networks and one directed acyclic graph (DAG) network were formed. First, in the anxiety network of chronic gastritis patients, dizziness was the most influential symptom. In the depression network of chronic gastritis patients, depressed affect and psychomotor retardation were the influential symptoms. Second, panic, easy fatiguability, weakness, palpitation, depressed affect, tachycardia, fatigue, and psychomotor agitation bridged the anxiety-depression network of chronic gastritis patients. Third, DAG networks showed that anxiousness and hopelessness could trigger other symptoms in the anxiety-depression networks of chronic gastritis patients. The current study provided insightful information on patients with chronic gastritis by examining the structures of symptoms.

HnRNPA2B1 ISGylation Regulates m6A-Tagged mRNA Selective Export via ALYREF/NXF1 Complex to Foster Breast Cancer Development.

Regulating nuclear export precisely is essential for maintaining mRNA homeostasis and impacts tumor progression. However, the mechanisms governing nuclear mRNA export remain poorly elucidated. Herein, it is revealed that the enhanced hypoxic long no-ncoding RNA (lncRNA prostate cancer associated transcript 6 (PCAT6) in breast cancer (BC) promotes the nuclear export of m6A-modified mRNAs, bolstering breast cancer stem cells (BCSCs) stemness and doxorubicin resistance. Clinically, hypoxic PCAT6 correlates with malignant BC features and poor prognosis. Mechanically, PCAT6 functions as a scaffold between interferon-stimulated gene 15 (ISG15) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), leading to ISGylation of hnRNPA2B1, thus protecting hnRNPA2B1 from ubiquitination-mediated proteasomal degradation. Interestingly, as an m6A reader, hnRNPA2B1 selectively mediates m6A-tagged mRNAs nuclear export via the Aly/REF export factor (ALYREF)/ nuclear RNA export factor 1 (NXF1) complex, which promotes stemness-related genes expression. HnRNPA2B1 knockdown or mRNA export inhibition can result in the retention of nuclear m6A-tagged mRNA associated with stemness maintenance, which suppresses BCSCs self-renewal and effectively improves the efficacy of doxorubicin therapy. These findings demonstrate the pivotal role of m6A-modified mRNA nuclear export in BC progression, highlighting that the inhibition of m6A-tagged mRNA and its nuclear export is a potential therapeutic strategy for the amelioration of cancer chemotherapy.

Precise Regulation on the Bond Dissociation Energy of Exocyclic C-N Bonds in Various N-Heterocycle Electron Donors via Machine Learning.

Heterocycles with saturated N atoms (HetSNs) are widely used electron donors in organic light-emitting diode (OLED) materials. Their relatively low bond dissociation energy (BDE) of exocyclic C-N bonds has been closely related to material intrinsic stability and even device lifetime. Thus, it is imperative to realize fast prediction and precise regulation of those C-N BDEs, which demands a deep understanding of the relationship between the molecular structure and BDE. Herein, via machine learning (ML), we rapidly and accurately predicted C-N BDEs in various HetSNs and found that five-membered HetSNs (5-HetSNs) have much higher BDEs than almost all 6-HetSNs, except emerging boron-N blocks. Thorough analysis disclosed that high aromaticity is the foremost factor accounting for the high BDE of 5-HetSNs, and introducing intramolecular hydrogen-bond or electron-withdrawing moieties could also increase BDE. Importantly, the ML models performed well in various realistic OLED materials, showing great potential in characterizing material intrinsic stability for high-throughput virtual-screening and material design efforts.

[Changes in protein requirements of elderly people over 5 years assessed using the indicator amino acid oxidation method].

OBJECTIVE: To evaluate the changes in protein requirements of the elderly during the past five years. METHODS: Based on the previous study of protein requirements of 14 elderly in 2017, 4 of these elderly(70-80 y) were included as study participants and protein requirements were re-evaluated using the indicator amino acid oxidation method. There were seven protein levels: 0.1, 0.3, 0.6, 0.9, 1.2, 1.5 and 1.8 g/(kg·d). Maintenance diets were given for the first two days of each protein level. A stable isotope study was conducted on the day 3, using L-~(13)C-phenylalanine as an indicator on the basis of an amino acid rationed diet, which was orally ingested into the body along with the amino acid rationed diet, and breath and urine samples were collected when the metabolism of L-~(13)C-phenylalanine reached steady state in the body. By measuring the kinetic parameters of labeled amino acids in the samples, a nonlinear mixed-effects model was constructed for the protein intake to be tested and the oxidation rate of labeled amino acids. The mean protein requirement of the study population was determined by the protein intake corresponding to the inflection point of the curve. RESULTS: Based on the production rate of ~(13)CO_2 in exhaled breath of four elderly people at different protein levels, the mean protein requirement was 1.05(95%CI 0.51-1.60) g/(kg·d). The protein recommended nutrient intake was 1.31(95%CI 0.64-2.00) g/(kg·d) was estimated by applying the coefficient of variation of the mean protein requirement to derive the recommended nutrient intake. CONCLUSION: Protein requirements in the elderly have increased over a five-year period and sarcopenia may be the main cause of increased protein requirements.

Long-term outcomes of survivors with influenza A H1N1 virus-induced severe pneumonia and ARDS: a single-center prospective cohort study.

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

Multi-User Computation Offloading and Resource Allocation Algorithm in a Vehicular Edge Network.

In Vehicular Edge Computing Network (VECN) scenarios, the mobility of vehicles causes the uncertainty of channel state information, which makes it difficult to guarantee the Quality of Service (QoS) in the process of computation offloading and the resource allocation of a Vehicular Edge Computing Server (VECS). A multi-user computation offloading and resource allocation optimization model and a computation offloading and resource allocation algorithm based on the Deep Deterministic Policy Gradient (DDPG) are proposed to address this problem. Firstly, the problem is modeled as a Mixed Integer Nonlinear Programming (MINLP) problem according to the optimization objective of minimizing the total system delay. Then, in response to the large state space and the coexistence of discrete and continuous variables in the action space, a reinforcement learning algorithm based on DDPG is proposed. Finally, the proposed method is used to solve the problem and compared with the other three benchmark schemes. Compared with the baseline algorithms, the proposed scheme can effectively select the task offloading mode and reasonably allocate VECS computing resources, ensure the QoS of task execution, and have a certain stability and scalability. Simulation results show that the total completion time of the proposed scheme can be reduced by 24-29% compared with the existing state-of-the-art techniques.

Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Comparison of the efficacy between the dual therapy of tegoprazan and the quadruple therapy of tegoprazan: A randomized, controlled, multicenter study.

INTRODUCTION: Tegoprazan (TPZ), a potassium-competitive acid blocker, exerts a strong acid-suppression effect and a rapid onset of action. However, research on TPZ-amoxicillin (TA) dual treatment is limited. Here, we compared the safety and efficacy of TPZ-amoxicillin dual treatment and TPZ, bismuth potassium citrate, amoxicillin, and clarithromycin (TBAC) quadruple therapy in patients newly diagnosed with H. pylori infection over a 14-day treatment period. METHODS: A total of 236 patients newly diagnosed with H. pylori were enrolled in this multi-center, prospective, open-label, and randomized controlled study. Patients randomly received either TA dual or TBAC quadruple therapy. The incidence of adverse reactions and treatment compliance were recorded and then analyzed. RESULTS: The intention-to-treat analysis revealed that H. pylori-eradication rates were 83.9% (95% confidence interval [CI] 78.2%-91.3%) and 81.4% (95% CI 74.2%-88.5%) for the TA and TBAC groups, respectively, with no statistically significant difference between them (P = 0.606). The per-protocol analysis revealed that the H. pylori-eradication rates were 88.3% and 84.8% for the TA and TBAC groups, respectively (P = 0.447). The incidence of adverse reactions was significantly lower in the TA group than in the TBAC group (4.2% vs. 15.3%, P = 0.004). Moreover, the TA group demonstrated substantially higher treatment compliance than the TBAC group (94.1% vs. 89.0%, P = 0.020). CONCLUSION: The TA dual therapy successfully eradicated H. pylori with a high eradication rate and a low incidence of adverse reactions. Therefore, this treatment is recommended as an alternative course for patients newly diagnosed with H. pylori infection.

Influence of disease course and comprehensive management on blood glucose level in children and adolescents with type 2 diabetes mellitus.

AIMS/INTRODUCTION: The aim of the present study was to evaluate the status of glycemic control, and assess the effects of the disease course and comprehensive management measures on the blood glucose level in children and adolescents with type 2 diabetes mellitus. MATERIALS AND METHODS: The study collected the clinical data of type 2 diabetes patients in Beijing Children's Hospital from January 2015 to September 2020. Patients were grouped based on the disease course to compare their glycated hemoglobin (HbA1c) level, islet ß-cell function, insulin resistance and comprehensive management measures. RESULTS: Of the 170 participants, the median disease course was 2.0 years (interquartile range [IQR] 1.0-4.0 years). The baseline HbA1c was 11.2% (IQR 9.2-12.4%). According to the grouping by the disease course, the median HbA1c was the lowest (5.7% [IQR 5.3-6.1%]) in the half-year course group and the highest in the 4-year course group (9.0 [IQR 6.8%-11.3%]). Compared with the group with a disease duration <2 years, patients in the >4 years group had a lower proportion of patients with HbA1c <7% (29.2% vs 66.2%), a lower homeostasis model assessment of ß-cell function, and a lower proportion with a controlled diet, moderate-intensity exercise, regular follow up and no drug treatment. We deemed HbA1c as the dependent variable, and found that disease duration, homeostasis model assessment of ß-cell function at follow up, continuous moderate-intensity exercise, regular review and treatment regimen were significant influencing factors for glycemic control. CONCLUSIONS: Children and adolescents with type 2 diabetes and a prolonged disease course showed poor glycemic control and decreased islet ß-cell function. A good lifestyle, especially moderate-intensity exercise, can help such cases better control their blood glucose level.

The Role of Dietary Intake of Live Microbes in the Association Between Leisure-Time Physical Activity and Depressive Symptoms: A Population-based Study.

Current research has shown promising associations between factors such as diet, total physical activity, and mental health outcomes, acknowledging the intricate interplay between these variables. However, the role of dietary intake of live microbes, coupled with leisure-time physical activity (LTPA), in their relationship to depressive symptoms necessitates further exploration. The present study examined a cohort of 25,747 individuals who participated in the NHANES between the years 2007 and 2018. Patient's Health Questionnaire (PHQ-9) was employed, whereby individuals scoring ≥ 10 were classified as exhibiting symptoms of depression. LTPA status was reported by the Global Physical Activity Questionnaire and calculated by MET-minutes/week. Foods consumed by participants were evaluated by live microbes per gram, which were categorized into three groups: low, medium, and high. After controlling for all covariates, findings indicated that LTPA was negatively associated with depressive symptoms [OR (95% CI): 0.983(0.976,0.990), p < 0.001]. Participating in more LTPA was positively correlated with consuming all three levels of dietary live microbes [low, ß (95% CI): 0.086(0.063, 0.109); medium, ß (95% CI): 0.009(0.007, 0.012); high, ß (95% CI): 0.002(0.001, 0.002)]. Moreover, taking more foods with medium live microbes was associated with lower depressive likelihood [OR (95% CI): 0.931(0.882,0.982), p = 0.010]. Intake of medium and high levels of live microbes mediated the association between LTPA and depressive symptoms by 4.15 % and 0.83 %, respectively. Dietary intake of foods containing medium and high levels of live microbes may be a mediator of LTPA's negative association with depressive symptoms.

Can the heptapeptide ASSIVSF of the ß2-adrenoceptor recognize ephedrine and pseudoephedrine epimers in a complex system?

Epimer separation is crucial in the field of analytical chemistry, separation science, and the pharmaceutical industry. No reported methods could separate simultaneously epimers or even isomers and remove other unwanted, co-existing, interfering substances from complex systems like herbal extracts. Herein, we prepared a heptapeptide-modified stationary phase for the separation of 1R,2S-(-)-ephedrine [(-)-Ephe] and 1S,2S-(+)-pseudoephedrine [(+)-Pse] epimers from Ephedra sinica Stapf extract and blood samples. The heptapeptide stationary phase was comprehensively characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The separation efficiency of the heptapeptide column was compared with an affinity column packed with full-length ß2-AR functionalized silica gel (ß2-AR column). The binding affinity of the heptapeptide with (+)-Pse was 3-fold greater than that with (-)-Ephe. Their binding mechanisms were extensively characterized by chromatographic analysis, ultraviolet spectra, circular dichroism analysis, isothermal titration calorimetry, and molecule docking. An enhanced hydrogen bonding was clearly observed in the heptapeptide-(+)-Pse complex. Such results demonstrated that the heptapeptide can recognize (+)-Pse and (-)-Ephe epimers in a complex system. This work, we believe, was the first report to simultaneously separate epimers and remove non-specific interfering substances from complex samples. The method was potentially applicable to more challenging sample separation, such as chiral separation from complex systems.