Facile synthesis of magnetic ionic covalent organic framework and dispersive magnetic solid phase extraction of aromatic amino acid oxidation products in thermally processed foods.

Aromatic amino acid oxidation products (AAAOPs) are newly discovered risk substances of thermal processes. Due to its significant polarity and trace level in food matrices, there are no efficient pre-treatment methods available to enrich AAAOPs. Herein, we proposed a magnetic cationic covalent organic framework (Fe3O4@EB-iCOF) as an adsorbent for dispersive magnetic solid-phase extraction (DMSPE). Benefiting from the unique charged characteristics of Fe3O4@EB-iCOF, AAAOPs can be enriched through electrostatic interaction and π-π interactions. Under the optimal DMSPE conditions, the combined HPLC-MS/MS method demonstrated good linearity (R2 ≥ 0.990) and a low detection limit (0.11-7.5 µg·kg-1) for AAAOPs. In addition, the method was applied to real sample and obtained satisfactory recoveries (86.8 % âˆ¼ 109.9 %). Especially, we applied this method to the detection of AAAOPs in meat samples and conducted a preliminarily study on its formation rules, which provides a reliable basis for assessing potential dietary risks.

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism.

Nowadays, presynaptic dopaminergic positron emission tomography, which assesses deficiencies in dopamine synthesis, storage, and transport, is widely utilized for early diagnosis and differential diagnosis of parkinsonism. This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism. We conducted a thorough literature search using reputable databases such as PubMed and Web of Science. Selection criteria involved identifying peer-reviewed articles published within the last 5 years, with emphasis on their relevance to clinical applications. The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis. Moreover, when employed in conjunction with other imaging modalities and advanced analytical methods, presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker. This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion. In summary, the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials, ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

Prevalence and potential influencing factors for social frailty among community-dwelling older adults: a systematic review and meta-analysis.

OBJECTIVE: To explore the prevalence and potential influencing factors of social frailty among community-dwelling older adults from a global perspective. METHODS: Systematic searches were conducted on multiple databases including CNKI, VIP, Wanfang Data, CBM, Pubmed, Cochrane Library, Web of Science, and Embase from inception to January 9, 2024. Two researchers performed a thorough literature search, gathered data, and independently evaluated the quality of the articles. RESULTS: 2,426 literatures were examined, 45 were found to meet the specified criteria for inclusion, encompassing 314,454 participants. The combined prevalence of social pre-frailty and social frailty among community-dwelling older adults were found to be 34.5% and 21.1%, respectively. Depression, activities of daily living (ADL), physical inactivity, motor deficits, cognitive impairment, and physical frailty are potential risk factors. CONCLUSIONS: Social pre-frailty and social frailty are frequent challenges faced by older adults living in the community. The prevalence of these conditions has been on the rise in recent years, underscoring the importance of implementing effective interventions. Early identification and intervention for individuals at risk of social frailty are essential for promoting healthy and active aging globally.

Effects of wheat germ diet on intestinal antioxidant capacity, immunological function and gut microbiota of Sichuan white geese.

Background: Wheat germ is known for its antioxidant, anti-inflammatory, and disease resistance properties in animals. However, its effect on the gut of Sichuan white geese remains unclear. Method: In this study, thirty 250-day-old geese were divided into three equal groups, the control group, LWG group (21.8% wheat germ) and HWG group (43.6% wheat germ), the experiment lasted 12 weeks. We assessed various aspects of geese intestinal health, including barrier function, digestibility, antioxidant capacity, immunity, microbiota, and metabolism. Results: The study revealed a significant increase in villus height (VH), villus height-to-crypt depth (VH/CD) ratio, amylase, and lipase activities in the duodenum and ileum, increased putrescine levels in the duodenum and jejunum, as well as spermidine levels in the jejunum (P < 0.05). LWG increased the total antioxidant capacity (T-AOC) in the duodenum, while decreasing levels of intestinal malondialdehyde (MDA), serum lipopolysaccharide (LPS), interleukin-6 (IL-6), and diamine oxidase (DAO) activity (P < 0.05). Furthermore, LWG increased the relative abundance of Oscillospiraceae_unclassified, Ligilactobacillus, and Roseburia, as well as increased levels of acetic acid, butyric acid, and valeric acid, while decreasing the relative abundance of Subdoligranulum, Flavonifractor, and Klebsiella. Additionally, we observed 17 up-regulated genes and 25 down-regulated genes in the jejunum, which are associated with the cell cycle and immunity. These genes play roles in pathways such as the p53 signaling pathway, cell cycle regulation, and pathways associated with immune modulation. On the other hand, HWG increased intestinal VH and spermidine levels, as well as amylase and lipase activities in the duodenum (P < 0.05). It also elevated ileal T-AOC and sIgA levels (P < 0.05), while reducing intestinal MDA content, serum LPS levels, DAO activity, and propionic acid in cecum contents (P < 0.05). Moreover, HWG increased the relative abundance of Ligilactobacillus, Oscillospiraceae_unclassified, and Roseburia (P < 0.05). Conclusion: Overall, wheat germ diets, particularly the LWG diet demonstrated the ability to enhance antioxidant capacity, digestibility, immunity, and barrier properties of the intestinal tract, while modulating the gut microbiota and metabolism. Therefore, wheat germ diets hold promise in improving intestinal health by preserving barrier function and regulating flora structure.

Design of linked-domain protein inhibitors of UBE2D as tools to study cellular ubiquitination.

Ubiquitin (Ub) is a post-translational modification that largely controls proteostasis through mechanisms spanning transcription, translation, and notably, protein degradation. Ub conjugation occurs through a hierarchical cascade of three enzyme classes (E1, E2, and E3s) involving >1000 proteins that regulate the ubiquitination of proteins. The E2 Ub-conjugating enzymes are the midpoint, yet their cellular roles remain under-characterized, partly due to a lack of inhibitors. For example, the cellular roles of the promiscuous E2 UBE2D/UBCH5 are not well described. Here, we develop a highly selective, multivalent, engineered protein inhibitor for the UBE2D family that simultaneously targets the RING- and backside-binding sites. In HeLa cells, these inhibitors phenocopy knockdown of UBE2D by reducing the IC50 to cisplatin and whole-cell proteomics reveal an increased abundance of ~20% of the identified proteins, consistent with reduced Ub degradation and proteotoxic stress. These precision tools will enable new studies probing UBE2D's central role in proteome management.

Amphiphilic disodium glycyrrhizin as a co-former for ketoconazole co-amorphous systems: Biopharmaceutical properties and underlying molecular mechanisms.

Co-amorphous systems (CAMs) have been extensively investigated to improve the dissolution of hydrophobic drugs. However, drug precipitation during the storage or dissolution of CAMs has still been a major challenge. Here, disodium glycyrrhizin (Na2GA) was first used as a co-former in CAMs based on its multiple hydroxyl groups and amphiphilic structure. Ketoconazole (KTZ), a BCS class II drug, was selected as a model drug. KTZ-Na2GA CAMs at mass ratios of 1:1, 1:2.5, 1:5 and 1:10 were prepared by the spray drying method and further characterised by PXRD and DSC. The 1:2.5, 1:5 and 1:10 groups exhibited significantly enhanced Cmax (all approximately 26.67-fold) and stable maintenance of supersaturation compared to the crystalline KTZ and the corresponding physical mixtures in non-sink dissolution tests, while the 1:1 group exhibited an unstable medium Cmax (all approximately 14.67-fold). The permeability tests revealed that the permeation rate of KTZ in KTZ-Na2GA CAMs under the concentration of Na2GA in solution above the critical micelle concentration (CMC) showed a significant downwards trend compared to that below CMC. The underlying molecular mechanisms were involved in molecular miscibility, hydrogen bond interactions, solubilisation and crystallisation inhibition by Na2GA. Pharmacokinetic studies demonstrated that the AUC0-∞ of KTZ in 1:1, 1:2.5, 1:5 and 1:10 groups were significantly higher than those of the crystalline KTZ group with 2.13-, 2.30-, 2.16- and 1.86-fold, respectively (p < 0.01). In conclusion, Na2GA has proven to be a promising co-former in CAMs to enhance hydrophobic drug dissolution and bioavailability. Its effect on intestinal permeation rate of drugs also deserves attention.

Physiologically-based pharmacokinetic/pharmacodynamic modeling of meropenem in critically ill patients.

This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic model (PBPK/PD) of meropenem for critically ill patients. A PBPK model of meropenem in healthy adults was established using PK-Sim software and subsequently extrapolated to critically ill patients based on anatomic and physiological parameters. The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between predicted and observed values of pharmacokinetic parameters Cmax, AUC0-∞, and CL to evaluate the accuracy of the PBPK model. The model was verified using meropenem plasma samples obtained from Intensive Care Unit (ICU) patients, which were determined by HPLC-MS/MS. After that, the PBPK model was combined with a PKPD model, which was developed based on f%T > MIC. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients. The developed PBPK model successfully predicted the meropenem disposition in critically ill patients, wherein the MFE average and GMFE of all predicted PK parameters were within the 1.25-fold error range. The therapeutic drug monitoring (TDM) of meropenem was conducted with 92 blood samples from 31 ICU patients, of which 71 (77.17%) blood samples were consistent with the simulated value. The TDM results showed that meropenem PBPK modeling is well simulated in critically ill patients. Monte Carlo simulations showed that extended infusion and frequent administration were necessary to achieve curative effect for critically ill patients, whereas excessive infusion time (> 4 h) was unnecessary. The PBPK/PD modeling incorporating literature and prospective study data can predict meropenem pharmacokinetics in critically ill patients correctly. Our study provides a reference for dose adjustment in critically ill patients.

Resolving the Trap Distribution of Chalcogenide-Based Heterojunctions via Optical Injection Deep Level Transient Spectroscopy.

Chalcogenide semiconductors have emerged as promising candidates for next-generation optoelectronics, mainly benefiting from their cost-effective processability, chemical versatility, and excellent stability. However, the device performance is limited by the complex defect characteristics, necessitating a detailed understanding of the defect density, types, and distribution. This study employs optical injection deep level transient spectroscopy to characterize the trap features of antimony bismuth sulfide-based heterojunctions. Photoexcitation offers the possibility to determine the spatial distribution of traps. It reveals distinct distributions of hole and electron traps. Short-wavelength light (570 nm) detects hole traps near the hole transport layer, while long-wavelength light (830 nm) identifies electron traps near the electron transport layer. Additional intermediate-wavelength tests (670 and 755 nm) and light field distribution simulation further elucidate the trap distribution. Transient absorption and transient photocurrent also support the non-uniform trap distribution within the chalcogenide-based photodiodes.

Potentially inappropriate prescribing among older adults with hypertension in China: prevalence and related comorbidities across different outpatient settings.

Purpose: Potentially inappropriate prescribing (PIP) is commonly encountered in older adults; yet, there is limited information on the occurrence of PIP among older adults with hypertension. This study aims to determine and compare the prevalence of PIP and its association with comorbidities in older adult outpatients with hypertension across hospitals and community health centers (CHCs). Methods: This 3-year (2015-2017) repeated cross-sectional study used electronic medical records from Shenzhen, China, involving 62 hospitals and 678 primary medical institutions. PIP was defined using the 2019 Beers Criteria. Older adults (≥65 years) with hypertension and at least one outpatient prescription were included. Modified Poisson regression analysis was used to assess the association between chronic comorbidities, healthcare settings, and PIP. Results: The prevalence of PIP in old adult outpatients with hypertension in 2015, 2016, and 2017 was 46.32%, 46.98%, and 46.58% in hospitals, with a sample size of 38,411, 46,235, and 50,495, respectively, and 29.14%, 26.66%, and 29.84% in CHCs, with a sample size of 26,876, 29,434, and 34,775 respectively. The top four most popular PIP in hospitals and CHCs was proton-pump inhibitors (PPIs), diuretics, benzodiazepines, and non-cyclooxygenase-selective non-steroidal anti-inflammatory drugs (NSAIDs), respectively. PIP was most associated with chronic gastrointestinal disease (adjusted prevalence ratio = 1.54, 95% confidence interval [CI] = 1.50-1.59) and mental and behavioral disorders (adjusted prevalence ratio = 1.49, 95% CI = 1.46-1.53) in hospitals and with mental and behavioral disorders (adjusted prevalence ratio = 1.99; 95% CI = 1.95-2.03) and musculoskeletal system and connective tissue disorders (adjusted prevalence ratio = 1.33; 95% CI = 1.31-1.36) in CHCs. The prevalence of PIP was significantly higher in hospital settings than in CHCs (adjusted prevalence ratio = 1.65; 95% CI = 1.63-1.66). Conclusion: Among older adult outpatients with hypertension in Shenzhen, PIP was more prevalent in hospitals than in CHCs. The comorbidities most strongly associated with PIP were chronic gastrointestinal disease and mental and behavioral disorders in hospitals and mental and behavioral disorders in CHCs. Clinical pharmacy integration needs to be considered to reduce inappropriate prescribing in this vulnerable population.

Safe Reinforcement Learning with Dual Robustness.

Reinforcement learning (RL) agents are vulnerable to adversarial disturbances, which can deteriorate task performance or break down safety specifications. Existing methods either address safety requirements under the assumption of no adversary (e.g., safe RL) or only focus on robustness against performance adversaries (e.g., robust RL). Learning one policy that is both safe and robust under any adversaries remains a challenging open problem. The difficulty is how to tackle two intertwined aspects in the worst cases: feasibility and optimality. The optimality is only valid inside a feasible region (i.e., robust invariant set), while the identification of maximal feasible region must rely on how to learn the optimal policy. To address this issue, we propose a systematic framework to unify safe RL and robust RL, including the problem formulation, iteration scheme, convergence analysis and practical algorithm design. The unification is built upon constrained two-player zero-sum Markov games, in which the objective for protagonist is twofold. For states inside the maximal robust invariant set, the goal is to pursue rewards under the condition of guaranteed safety; for states outside the maximal robust invariant set, the goal is to reduce the extent of constraint violation. A dual policy iteration scheme is proposed, which simultaneously optimizes a task policy and a safety policy. We prove that the iteration scheme converges to the optimal task policy which maximizes the twofold objective in the worst cases, and the optimal safety policy which stays as far away from the safety boundary. The convergence of safety policy is established by exploiting the monotone contraction property of safety self-consistency operators, and that of task policy depends on the transformation of safety constraints into state-dependent action spaces. By adding two adversarial networks (one is for safety guarantee and the other is for task performance), we propose a practical deep RL algorithm for constrained zero-sum Markov games, called dually robust actor-critic (DRAC). The evaluations with safety-critical benchmarks demonstrate that DRAC achieves high performance and persistent safety under all scenarios (no adversary, safety adversary, performance adversary), outperforming all baselines by a large margin.

Preparation of Double-Layer Composite Coffee Filtration Nonwovens.

The coffee industry is developing rapidly in the world, and the use of coffee filtration nonwovens (CFNs) is becoming more and more extensive; however, there is a lack of standards and research for its production and trade, and the quality of related products on the market is uneven at present. Here, eight double-layer composite coffee filtration nonwovens (D-LCCFNs) were prepared by using 5 g/m2 and 10 g/m2 polypropylene (PP) melt-blown nonwovens (MNs), 20 g/m2 PP spunbonded nonwovens and 20 g/m2 viscose/ES fiber chemically bonded nonwovens, and the physical properties, morphology and the filtration effect of coffee and purified water for the prepared samples were tested. It was found that the surface density of the microfiber layer (MNs) in the D-LCCFNs was negatively correlated with the coffee filtration rate; when the microfiber layer in the D-LCCFNs was in direct contact with the coffee, the liquid started to drip later, and the filtration rate of the coffee was slower; the filtration rate of the samples with the viscose/ES chemically bonded nonwovens was very fast. However, the samples without viscose/ES fibers basically did not filter pure water much, but they could filter out the coffee liquid normally, and the samples' hydrophilicity increased significantly after filtering coffee.

High-Entropy-Inspired Multicomponent Electrical Double Layer Structure Design for Stable Zinc Metal Anodes.

Regulating the electrical double layer (EDL) structure can enhance the cycling stability of Zn metal anodes, however, the effectiveness of this strategy is significantly limited by individual additives. Inspired by the high-entropy (HE) concept, we developed a multicomponent (MC) EDL structure composed of La3+, Cl-, and BBI anions by adding dibenzenesulfonimide (BBI) and LaCl3 additives into ZnSO4 electrolytes (BBI/LaCl3/ZnSO4). Specifically, La3+ ions accumulate within EDL to shield the net charges on the Zn surface, allowing more BBI anions and Cl- ions to enter this region. Consequently, this unique MC EDL enables Zn anodes to simultaneously achieve uniform electric field, robust SEI layer, and balanced reaction kinetics. Moreover, the synergistic parameter-a novel descriptor for quantifying collaborative improvement-was first proposed to demonstrates the synergistic effect between BBI and LaCl3 additives. Benefitting from these advantages, Zn metal anodes achieved a high reversibility of 99.5% at a depth of discharge (DoD) of 51.3%, and Zn|MnO2 pouch cells exhibited a stable cycle life of 100 cycles at a low N/P ratio of 2.9.

Evaluating the protective effectiveness and risk factors of ursodeoxycholic acid on COVID-19 among outpatients.

Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure. Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients. Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1 month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent. Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA's effectiveness in COVID-19 prevention or treatment.

Cascading Failure in Cyber-Physical Systems: A Review on Failure Modeling and Vulnerability Analysis.

Cascading failures pose a significant security threat to networked systems, with recent global incidents underscoring their destructive potential. The security threat of cascading failures has always existed, but the evolution of cyber-physical systems (CPSs) has introduced novel dimensions to cascading failures, intensifying their threats owing to the intricate fusion of cyber and physical domains. Addressing these threats requires a nuanced understanding achieved through failure modeling and vulnerability analysis. By analyzing the historical failures in different CPSs, the cascading failure in CPSs is comprehensively defined as a complicated propagation process in coupled cyber and physical systems, initialized by natural accidents or human interference, which exhibits a progressive evolution within the networked structure and ultimately results in unexpected large-scale systemic failures. Subsequently, this study advances the development of instructions for modeling cascading failures and conducting vulnerability analyses within CPSs. The examination also delves into the core challenges inherent in these methodologies. Moreover, a comprehensive survey and classification of extant research methodologies and solutions are undertaken, accompanied by a concise evaluation of their advancements and limitations. To validate the performance of these methodologies, numerical experiments are conducted to ascertain their distinct features. In conclusion, this article advocates for future research initiatives, particularly emphasizing the exploration of uncertainty analysis, defense strategies, and verification platforms. By addressing these areas, the resilience of CPSs against cascading failures can be significantly enhanced.

Synergistic effect between S and Te enhancing the electrochemical behavior of heteroatomic TeS-x cathodes in aqueous Zn-TeS batteries.

Aqueous Zn-S batteries (AZSBs) have garnered increasing attention in the energy storage field owing to their high capacity, energy density, and cost effectiveness. Nevertheless, sulfur (S) cathodes face challenges, primarily stemming from sluggish reaction kinetics and the formation of an irreversible byproduct (SO42-) during the charge, hindering the progress of AZSBs. Herein, Te-S bonds within S-based cathodes were introduced to enhance electron and ion transport and facilitate the conversion reaction from zinc sulfide (ZnS) to S. This was achieved by constructing heteroatomic TeS-x@Ketjen black composite cathodes (HM-TeS-x@KB, where x  = 36, 9, and 4). The HM-TeS-9@KB electrode exhibits long-term cycling stability, maintaining a capacity decay rate of 0.1 % per cycle over 450 cycles at a current density of 10 A g-1. Crucially, through a combination of experimental data analysis and theoretical calculations, the impact mechanism of Te on the charge and discharge of S active materials within the HM-TeS-9@KB cathode in AZSBs was investigated. The presence of Te-S bonds boost the intrinsic conductivity and wettability of the HM-TeS-9@KB cathode. Furthermore, during the charge, the interaction of preferentially oxidized Te with S atoms within ZnS promotes the oxidation reaction from ZnS to S and suppresses the irreversible side reaction between ZnS and H2O. These findings indicate that the heteroatomization of chalcogen S molecules represents a promising approach for enhancing the electrochemical performance of S cathodes in AZSBs.

Shenling Baizhu Decoction treats ulcerative colitis of spleen-deficiency and dampness obstruction types by targeting 'gut microbiota and galactose metabolism-bone marrow' axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenlin Baizhu Decoction (SLBZD), which comes from 'Taiping Huimin Heji Ju Fang', belongs to a classical prescription for treating spleen deficiency and dampness obstruction (SQDDS)-type ulcerative colitis (UC) in traditional Chinese medicine. However, the mechanism of SLBZD in treating UC with SQDDS remains unclear. AIM OF THE STUDY: This study aims to investigate the mechanism of SLBZD against SQDDS-type UC of based on the "gut microbiota and metabolism - bone marrow" axis to induce endogenous bone marrow mesenchymal stem cells (BMSCs) homing. MATERIALS AND METHODS: Ultra-performance liquid chromatography-mass spectrometry was used to analysis of SLBZD qualitatively. The efficacy of SLBZD in SQDDS-type UC was evaluated based on the following indicators: the body weight, colon length, disease activity index (DAI) score, Haemotoxylin and Eosin (H&E) pathological sections, and intestinal permeability proteins (occluding and ZO-1). 16S rRNA gene sequencing and non-target metabolomics were performed to identify gut microbiota changes and its metabolites in feces, respectively. BMSCs in each group was collected, cultured, and analyzed. Optimal passaged BMSCs were injected by tail vein into UC rats of SQDDS types. BMSCs homing to the colonic mucosal tissue was observed by immunofluorescent. Finally, the repairing effect of BMSCs homing to the colonic mucosal tissue after SLBZD treatment was analyzed by transmission electron microscopy, qRT-PCR, and immunohistochemistry. RESULTS: SLBZD effectively improved the colonic length and the body weight, reduced DAI and H&E scores, and increased the expression of the intestinal permeability proteins, including occluding and ZO-1, to treat SQDDS-type UC. After SLBZD treatment, the α-diversity and ß-diversity of the gut microbiota were improved. The differential microbiota was screened as Aeromonadaceae, Lactobacillaceae, and Clostridiaceae at the family level, and Aeromonas, Lactobacillus, Clostridium_sensu_stricto_1 at the genus level. Meanwhile, the main metabolic pathway was the galactose metabolism pathway. SLBZD treatment timely corrected the aberrant levels of ß-galactose in peripheral blood and bone marrow, senescence-associate-ß-galactosidase in BMSCs, and galactose kinase-2, galactose mutase, and galactosidase beta-1 in peripheral blood to further elevate the expression levels of senescence-associated (SA) proteins (p16, p53, p21, and p27) in BMSCs. The Spearman's correlation analysis demonstrated the relationship between microbiota and metabolism, and the relationship between the galactose metabolism pathway and SA proteins. After BMSCs in each group injection via the tail vein, the pharmacodynamic effects were consistent with those of SLBZD in SQDDS-type UC rats. Furthermore, BMSCs have been homing to colonic mucosal tissue. BMSCs from the SLBZD treatment group had stronger restorative effects on intestinal permeability function due to increasing protein and mRNA expressions of occludin and ZO-1, and decreasing the proteins and mRNA expressions of SDF-1 and CXCR4 in colon. CONCLUSIONS: SLBZD alleviated the damaged structure of gut microbiota and regulated their metabolism, specifically the galactose metabolism, to treat UC of SDDOS types. SLBZD treatment promotes endogenous BMSCs homing to colonic mucosal tissue to repaire the intestinal permeability. The current exploration revealed an underlying mechanism wherein SLBZD activates endogenous BMSCs by targeting 'the gut microbiota and its metabolism-bone marrow' axis and repairs colonic mucosal damage to treat SDDOS-type UC.

Urinary concentrations of mineral elements and their predictors in pregnant women in Jinan, China.

BACKGROUND: The essential mineral elements play important roles in proper growth, development and maintenance of physiological homeostasis of an organism. Women are at greater risk of mineral deficiency during pregnancy. However, the predictors of mineral element levels in pregnant women remain unclear. This study was conducted to determine the urinary levels of calcium (Ca), iron (Fe), copper (Cu), manganese (Mn) and selenium (Se) in women during early pregnancy and to explore the predictors of urinary exposure to each mineral element and high co-exposure to mineral element mixture. METHODS: 298 pregnant women in first trimester were recruited when they attended antenatal care in a hospital in Jinan, Shandong Province, China. We collected their spot urine samples and questionnaire data on their sociodemographic characteristics, lifestyle habits, food and dietary supplement intake, and residential environment. The concentrations of Ca, Fe, Cu, Mn and Se in all urine samples were measured. LASSO regression, multiple linear regression and binary logistic regression were used to analyze the predictors affecting mineral element levels. RESULTS: The geometric means of creatinine-corrected Ca, Fe, Cu, Mn and Se concentrations were 99.37 mg/g, 1.75 µg/g, 8.97 µg/g, 0.16 µg/g and 16.83 µg/g creatinine, respectively. Factors that influenced the concentrations of individual mineral element were as follows: (1) Se and Ca concentrations increased with maternal age; (2) women taking tap water as family drinking water had higher Ca levels and those taking polyunsaturated fatty acids intermittently had higher Cu levels; (3) Fe was adversely related to consumption frequency of barbecued foods; (4) Pregnant women with more frequent consumption of shellfish/shrimp/crab and living near green spaces or parks had higher Mn exposure, and those with higher frequency of meat consumption had lower Mn exposure. In addition, maternal age and the frequency of egg consumption were associated with odds of exposure to a mixture of high Ca, Fe, Cu and Se. CONCLUSIONS: The pregnant women in this study had comparable concentrations of urinary Cu and Se but lower concentrations of Ca, Fe and Mn compared with those in other areas. Predictors of urinary mineral elements included maternal age (Se and Ca), type of domestic drinking water (Ca), consumption frequency of barbecued food (Fe), polyunsaturated fatty acid use (Cu), the presence of urban green spaces or parks near the home and frequency of meat and shellfish/shrimp/crab intake (Mn). Moreover, maternal age and egg consumption frequency were significant predictors of high-level co-exposure to urinary Ca, Fe, Cu and Se.

Corrigendum: Blood glucose to predict symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke with large infarct core: a prospective observational study.

[This corrects the article DOI: 10.3389/fneur.2024.1367177.].