Bioinspired core-shell microparticle for dual-delivery of prebiotic and probiotic for the treatment of ulcerative colitis.

Lactiplantibacillus plantarum (LP) is a well-known probiotic strain that has a beneficial effect in preventing ulcerative colitis. However, delivering a sufficient number of viable LP to the colon still face challenges due to its vulnerability to the highly complex intestinal flora ecosystem. Herein, we present a centrifuge-driven micronozzle system designed for double-layered core-shell alginate microcapsules (DAM), which can serve as an effective carrier for dual delivery of resistant starch nanoparticles (RSNP, prebiotic) and LP (probiotics) for the treatment of colitis. This system enables precise loading of LP and RSNP within the core and shell regions of DAM, respectively. The resulting LP/RS@DAM exhibited a high encapsulation efficiency of LP (108 CFU per bead), in which the dense distribution of RSNP in the shell effectively protected LP against acidic conditions (pH 2) and maintained the cell viability up to 52 % even after long-term storage for 30 days. Furthermore, LP/RS@DAM effectively enhances the production of short-chain fatty acids, leading to a reduction in inflammatory cytokines and restoration of intestinal microbial diversity in dextran sulfate sodium (DSS)-induced colitis. We believe that this innovative approach would offer a potential solution for improving colitis management and paving the way for tailored therapeutic interventions in gastrointestinal disorders.

Integrating network pharmacology and experimental validation to investigate the effects and mechanism of Renshen Shouwu decoction for ameliorating Alzheimer's disease.

CONTEXT: The mechanism of Renshen Shouwu Decoction (RSSW) in treating Alzheimer's disease (AD) remains unknown. OBJECTIVE: This study investigates the effects and mechanism of RSSW for ameliorating AD. MATERIALS AND METHODS: Ten SAMR1 mice and 40 SAMP8 mice were divided into five groups: control (SAMR1), model (SAMP8), positive drug (Donepezil, 1.3 mg/kg/d), and RSSW (Low-dose, 117 mg/kg/d; High-dose, 234 mg/kg/d). Starting from 6 months of age, the medications were administered intragastrically for a total of 60 days. Subsequently, memory improvement in rapidly aging mice was assessed using the novel object recognition test and Morris water maze test. Through the identification of absorbed blood components and analysis of network pharmacology, active ingredients and potential targets involved in the treatment of AD were identified. Finally, AD-related biological indicators were detected using western blotting and ELISA. RESULT: Our results demonstrated that RSSW effectively ameliorated memory impairments, inhibited tau hyperphosphorylation, and reduced ß-amyloid plaque deposition in SAMP8 mice. Thirty absorbed blood components in RSSW were identified, revealing identified 96 major targets that play a key role in alleviating AD. Notably, the obtained main targets were highly enriched in SIRT1-mediated signaling pathways. Subsequent experimental validation confirmed that RSSW activated the SIRT1/NF-κB, SIRT1/AMPK, and SIRT1/p53 signaling cascades. Nine potential active ingredients were predicted through molecular docking. DISCUSSION AND CONCLUSIONS: Our research findings suggest the mechanism of RSSW treatment for AD, which ameliorates memory impairments by reducing cortical tissue inflammation and apoptosis.

Bioaccessibility and bioavailability of exogenous and endogenous toxic substances in traditional Chinese medicine and their significance in risk assessment.

Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry.

Effect of Wei Qi Booster on immune and anti-oxidative function in aged mice.

This research was conducted to examine the impact of Wei Qi Booster (WQB) on immune parameters and anti-oxidative function in aged mice. Fifty aged mice were randomly assigned to five different groups. Group A was designated as the control group. Mice in Group B were receiving Levamisole at 10 mg/kg body weight. Each mouse in groups C, D and E received 0.1, 1, and 2% WQB, respectively. Another ten young mice, designated as group F, were fed regularly. The mice were fed according to the above methods for 28 days. Results showed that relative to the control group, the body weight and immune organs indexes experienced a substantial rise in the group with 1% WQB. In addition, 1% WQB could improve the activity of SOD and reduce the MDA levels. Expressions of CD4 and sIgA increased while CD8 decreased in the jejunum of aged mice treated with WQB. IL2 and IFN-γ levels increased in the 1% WQB group, showing no notable difference compared to the young mice group. The results demonstrated that WQB can elevate immune levels and enhance anti-oxidative functions in aged mice.

Cushing's syndrome caused by giant Ewing's sarcoma of the kidney: A case report and review of literature.

BACKGROUND: Primary renal Ewing's sarcoma (ES) is extremely rare, and only two cases causing Cushing's syndrome (CS) have been reported to date. We report that the case of an 18-year-old patient is diagnosed primary renal ES with typical CS characterized by purple stripes, weight gain, and hypertension. CASE SUMMARY: CS was first diagnosed by laboratory testing. A huge tumor was revealed in the kidney following an imaging examination. Moreover, brain and bone metastases were observed. After comprehensive treatment, primarily based on surgery, primary renal ES was pathologically diagnosed with a typical EWSR1-FLI1 genetic mutation through genetic testing. Furthermore, the glucocorticoid level returned to normal. By the ninth postoperative month of follow-up, the patient was recovering well. Cushing-related symptoms had improved, and a satisfactory curative effect was achieved. CONCLUSION: Primary renal ES, a rare adult malignant tumor, can cause CS and a poor prognosis.

Warthin tumor concomitant with mantle cell lymphoma: a case report and review of literature.

RATIONALE: Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. PATIENT CONCERNS: A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. DIAGNOSIS: Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. INTERVENTIONS: The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. OUTCOMES: Currently, the patient demonstrates a stable disease by clinical evaluation. LESSONS: To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.

Jianpi Jiedu Recipe Inhibits Proliferation through Reactive Oxygen Species-Induced Incomplete Autophagy and Reduces PD-L1 Expression in Colon Cancer.

BACKGROUND: Jianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear. METHODOLOGY: CCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. The RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. The xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo. RESULTS: JPJDR has an excellent inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly, and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1. Meanwhile, JPJDR can exert an excellent therapeutic effect in xenograft tumor mice. CONCLUSION: JPJDR is a low-toxicity and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.

Antibacterial and antioxidant phlorizin-loaded nanofiber film effectively promotes the healing of burn wounds.

Burns usually result in damage and loss of skin forming irregular wound wounds. The lack of skin tissue protection makes the wound site highly vulnerable to bacterial infections, hindering the healing process. However, commonly used wound dressings do not readily provide complete coverage of irregular wounds compared to regular wounds. Therefore, there is an urgent need to prepare a wound dressing with high antimicrobial efficacy for the administration of drugs to irregular wounds. In this study, a chitosan (CS)/polyvinylpyrrolidone (PVP) composite nanofiber membrane (CS/PVP/Phlorizin) loaded with root bark glycosides (Phlorizin) was developed using an electrostatic spinning technique. The incorporation of phlorizin, a natural antioxidant, into the fiber membranes notably boosted their antimicrobial and antioxidant capabilities, along with demonstrating excellent hydrophilic characteristics. In vitro cellular experiments showed that CS/PVP/Phlorizin increased Hacat cell viability with the presence of better cytocompatibility. In scald wound healing experiments, Phlorizin-loaded nanofibrous membranes significantly promoted re-epithelialization and angiogenesis at the wound site, and reduced the inflammatory response at the wound site. Therefore, the above results indicate that this nanofiber membrane is expected to be an ideal dressing for burn wounds.

Cytotoxicity evaluation of organophosphorus flame retardants using electrochemical biosensors and elucidation of associated toxic mechanisms.

In recent years, organophosphorus flame retardants (OPFRs) have been widely used as substitutes for brominated flame retardants with excellent properties, and their initial toxicological effects on the water ecosystem and human health have gradually emerged. However, to date, research on the cytotoxicity and health risks of OPFRs is still limited. Therefore, this study aims to systematically explore the cytotoxic effects and toxic mechanisms of OPFRs on cells. Human liver cancer (HepG2) cells were adopted as an ideal model for toxicity evaluation due to their rapid growth and metabolism. This study proposes a sensitive electrochemical cell-based sensor constructed on a graphitized multi-walled carbon nanotube/ionic liquid/gold nanoparticle-modified electrode. The sensor was used to detect the cytotoxicity of tri(2-butylxyethyl) phosphate (TBEP), tributyl phosphate (TnBP), triphenyl phosphate (TPhP), tri(1,3-dichloro-2-propyl) phosphate (TDCIPP), tri(2-chloropropyl) phosphate (TCPP) and tri(2-chloroethyl) phosphate (TCEP) in the liquid medium, providing insight into their toxicity in water environments. The half-maximal inhibitory concentration (IC50) of TBEP, TnBP, TPhP, TDCIPP, TCPP and TCEP on HepG2 cells were 179.4, 194.9, 219.8, 339.4, 511.8 and 859.0 µM, respectively. Additionally, the cytotoxic mechanism of six OPFRs was discussed from the perspective of oxidative stress and apoptosis, and four indexes were correlated with toxicity. Furthermore, transcriptome sequencing was conducted, followed by a thorough analysis of the obtained sequencing results. This analysis demonstrated a significant enrichment of the p53 and PPAR pathways, both of which are closely associated with oxidative stress and apoptosis. This study presents a simplified and efficient technique for conducting in vitro toxicity studies on organophosphorus flame retardants in a water environment. Moreover, it establishes a scientific foundation for further investigation into the mechanisms of cytotoxicity associated with these compounds.

Quaternized oxidized sodium alginate injectable hydrogel with high antimicrobial and hemostatic efficacy promotes diabetic wound healing.

In this paper, a hydrogel material with efficient antibacterial, hemostatic, self-healing, and injectable properties was designed for the treatment of diabetic wounds. Firstly, quaternary ammonium salts were grafted with oxidized sodium alginate, and quaternized oxidized sodium alginate (QOSA) was synthesized. Due to the introduction of quaternary ammonium group it has antibacterial and hemostatic effects, at the same time, due to the presence of aldehyde group it can be reacted with carboxymethyl chitosan (CMCS) to form a hydrogel through the Schiff base reaction. Furthermore, deer antler blood polypeptide (DABP) was loaded into the hydrogel (QOSA&CMCS&DABP), showing good swelling ratio and bacteriostatic effect. In vitro and in vivo experiments demonstrated that the hydrogel not only quickly inhibited hepatic hemorrhage in mice and reduced coagulation index and clotting time in vitro, but also significantly enhanced collagen deposition at the wound site, accelerating wound healing. This demonstrates that the multifunctional hydrogel materials (QOSA&CMCS&DABP) have promising applications in the acceleration of skin wound healing and antibacterial promotion.

A novel bioaccessibility-based probabilistic risks assessment of potentially toxic elements (PTEs) in earthworm.

Introduction: Early risk assessment studies usually based on total heavy metal (loid) contents, inevitably leading to an overestimation of the health risks. In addition, inputs are represented as single-point estimates in deterministic models, leading to underestimation or overestimation of the health risks. Methods: To overcome these barriers, a novel probabilistic risk assessment strategy based on the combinational use of bioaccessibility and Monte Carlo simulation was developed to assess heavy metal (loid) associated health risks of earthworms in this study. To obtain a realistic and robust probabilistic risk assessment, heavy metal (loid) exposure duration and frequency were determined using our questionnaire data. Results: As a result, the mean gastrointestinal bioaccessibility was in the order: Cd > As > Cu > Hg. The mean hazard index (HI) values for investigated metal (loid)s were 0.65 and 0.59 for male and female, respectively, demonstrating an acceptable health risk in an average community. However, the 90th percentile of HI values was 1.87 and 1.65 for male and female, respectively. And the total non-cancer risks of heavy metal (loid) exposure exceeded the acceptable threshold for 19.9% and 17.8% of male and female, respectively. In addition, the total cancer risk (TCR) value through co-exposure to As and Cd suggested that the carcinogenic risks may be of concern for average exposure population. Sensitivity analyses revealed that the exposure frequency and bioaccessible As concentration were the dominant contributors to the total risk variance, which provided meaningful implications for environmental management. Conclusion: Altogether, the refined strategy based on bioaccessibility and Monte Carlo simulation is the first of its kind, such effort attempts to scientifically guide the rational clinic use of TCM and the improvement of population-health.

Facile Synthesis of Multifunctional Mesoporous Starch-Based Microparticle for Effective Hemostasis and Wound Healing.

Uncontrolled hemorrhage and infection are the principal causes of mortality associated with trauma in both military and civilian medical settings. Modified starch granules have emerged as a safe hemostatic agent for irregular and noncompressible wounds, but their performance is constrained by limited hemostasis efficiency and modest antibacterial activity. This study reported a directed self-assembly approach for a multifunctional mesoporous starch-based microparticle loaded with chitosan and calcium ions (Ca@MSMP) used for rapid hemostasis and wound healing. Directed self-assembly of uniform Ca@MSMP with a hierarchical hollow structure in the presence of chitosan was confirmed by scanning electron microscopy (SEM) analysis and pore structure analysis. The resulting Ca@MSMP exhibited a well-defined spherical shape and uniform size of 1 µm and demonstrated excellent antibacterial activity (>95%) without hemolytic activity. Importantly, Ca@MSMP enhanced blood coagulation and platelet aggregation via the synergistic effect of rapid calcium release and chitosan-mediated electrostatic interactions, leading to a significant decrease in blood loss and reduction in hemostasis time in rat tail amputation and liver injury models. In comparative analyses, Ca@MSMP significantly outperformed the commercial hemostatic agent Quickclean, notably enhancing the healing of full-thickness skin wounds in vivo by effectively preventing infection. These results underscore the potential of this innovative hemostatic material in diverse clinical scenarios, offering effective solutions for the management of bleeding in wounds that are irregularly shaped and noncompressible.

A Sustainable and Cost-Effective Nitrogen-Doped Three-Dimensional Porous Carbon for High-Performance Lithium-Sulfur Batteries.

Affordable clean energy is one of the major sustainable development goals that can transform our world. At present, researchers are working to develop cheap electrode materials to develop energy storage devices, the Lithium-sulfur (Li-S) battery is considered a promising energy storage device owing to its excellent theoretical specific capacity and energy density. Herein, utilizing the ramie degumming waste liquid as raw materials, after freeze-drying and high-temperature calcination, a sustainable and cost-effective three-dimensional (3D) porous nitrogen-doped ramie carbon (N-RC) was synthesized. The N-RC calcined at 800 °C (N-RC-800) shows a superior high specific surface area of 1491.85 m2 ⋅ g-1 and a notable high pore volume of 0.90 cm3 ⋅ g-1. When employed as a sulfur host, the S@N-RC-800 cathode illustrates excellent initial discharge capacity (1120.6 mAh ⋅ g-1) and maintains a reversible capacity of 625.4 mAh ⋅ g-1 after 500 cycles at 1 C. Simultaneously, the S@N-RC-800 cathode also shows excellent coulombic efficiency and ideal rate performance. Such exceptional electrochemical performance of S@N-RC-800 can be primarily attributable to N-RC's high specific surface area, high porosity, and abundant polar functional groups. This green and low-cost synthesis strategy offers a new avenue for harnessing the potential of waste biomass in the context of clean energy storage.

Hierarchical mesoporous TiO2/starch-based microparticles used as an efficient and reusable adsorbent for removal of water-soluble dye.

The widespread use of organic dyes in various industrial applications, driven by rapid industrialization, has become a significant environmental concern. Thus, highly efficient and reusable adsorbent for removal of pollutant dyes have gained increasing attention in water treatment. In this study, we present TiO2 nanoparticle-embedded mesoporous starch-based microparticle (TiO2@MSMP) with hierarchical rose-like structure were synthesis by using acetone precipitation of short-chain glucan (SCG) obtained from waxy maize starch. The resulting TiO2@MSMP exhibits an A-type crystalline polymorph and mean particle size of approximately 2 µm, displaying a type IV adsorption isotherm with a mean pore diameter of 19 nm and an average surface area of 12.34 m2/g. The adsorption ability of TiO2@MSMP towards methyl orange (MO) and crystal violet (CV) were 85.8 mg/g and 103.8 mg/g, respectively. The reusability of TiO2@MSMP was achieved by UV irradiation, which resulted in photodegradation of the adsorbed dye over 80 % while maintaining good absorption ability and structural stability during the recycling process. Given its cost-effectiveness, high adsorption capacity, and excellent reusability, TiO2@MSMP holds promise as an effective and environmentally friendly adsorbent with significant potential for removing dyes from aqueous solutions and purifying water.

Parental and Adolescents' Anxiety during the COVID-19 Outbreak in Rural China: The role of Parent-child Communication.

Purpose: It has been suggested that the intergenerational transmission of anxiety may be an important contributor to the high prevalence of anxiety in adolescents. The objectives of this study are to examine whether and how parental anxiety is related to adolescent's anxiety and to explore the associations of parental anxiety and parent-child communication with adolescents' anxiety across different grades. Methods: The current survey was conducted online from February 8th to February 27th, 2020.The questionnaires were distributed and retrieved through a web-based platform. A total of 6196 Chinese rural adolescents from grade seven to twelve (age ranging from 11 to 18 years old) were included. Results: In this study, parental anxiety was significantly associated with higher adolescent anxiety (ß = 0.14, p < 0.001) and this association was statically strongest at grade twelve. Besides, children with problematic parent-child communication related to COVID-19 reported elevated anxiety (ß = 0.05, p < 0.01). In contrast, effective parent-child communication about COVID-19 mitigated the level of anxiety transmitted from parent to child (ß = -0.04, p < 0.05). Conclusions: During the COVID-19 epidemic, parents' anxiety was related to adolescents' anxiety. In addition, parent-child communication plays a moderating role in the above relationship. These findings emphasize the importance of implementing more psycho-education programs that specifically target parents' emotion regulation and effective communication abilities to ameliorate the psychopathological symptoms of parents and their children. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00609-y.

Chitosan-modified dihydromyricetin liposomes promote the repair of liver injury in mice suffering from diabetes mellitus.

Liver injury caused by type-II diabetes mellitus (DM) is a significant public-health concern worldwide. We used chitosan (CS) to modify dihydromyricetin (DHM)-loaded liposomes (DL) through charge interaction. The effect of CS-modified DL (CDL) on liver injury in mice suffering from DM was investigated in vivo and in vitro. CDL exhibited superior antioxidant capacity and stability. Pharmacokinetic analyses revealed a 3.23- and 1.92-fold increase in the drug concentration-time curve (953.60 ± 122.55 ng/mL/h) in the CDL-treated group as opposed to the DHM-treated group (295.15 ± 25.53 ng/mL/h) and DL-treated group (495.31 ± 65.21 ng/mL/h). The maximum drug concentration in blood (Tmax) of the CDL group saw a 2.26- and 1.21-fold increase compared with that in DHM and DL groups. We observed a 1.49- and 1.31-fold increase in the maximum drug concentration in blood (Cmax) in the CDL group compared with that in DHM and DL groups. Western blotting suggested that CDL could alleviate liver injury in mice suffering from DM by modulating inflammatory factors and the transforming growth factor-ß1/Smad2/Smad3 signaling pathway. In conclusion, modification of liposomes using CS is a viable approach to address the limitations of conventional liposomes and insoluble drugs.

Cytotoxic xanthanolide sesquiterpenes from the fruits of Xanthium italicum Moretti.

One previously undescribed xanthanolide sesquiterpene dimer pungiolide P (1), possessing an unprecedented scaffold with a 5/7/5/7/5 ring system skeleton and its intermediate pungiolide Q (2), ten xanthanolide sesquiterpenes (3-12), two eudesmene sesquiterpene derivatives (13-14), one phenylpropionic acid derivative (15), together with eleven known compounds (16-26) were obtained from the fruits of Xanthium italicum Moretti. A possible biosynthetic pathway for pungiolide P (1) was also proposed, which was supported by its bio-synthetic intermediate (2). Compounds 1, 4-5, 18-21, and 25 exhibited cytotoxic activity against a variety of human cancer cell lines. Furthermore, compounds 1, 4-5, could cause blockage of the cell cycle in the G2/M phase and induce apoptosis in H460 cells. Notably, pungiolide P (1) exhibited significantly superior cytotoxicity compared to previously reported compounds, providing valuable insights for natural anti-tumor sources.

Bioactive prenylated c6-c3 derivatives from the roots of Illicium brevistylum.

Three new prenylated C6-C3 compounds (1-3), together with two known prenylated C6-C3 compounds (4-5) and one known C6-C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 µM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4-6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 µM.

Vitamin D supplementation for cardiometabolic risk markers in pregnant women based on the gestational diabetes mellitus or obesity status : a randomized clinical trial.

PURPOSE: Women with gestational diabetes mellitus (GDM) or obesity are vulnerable to impaired gestational cardiovascular health (CVH) and cardiovascular disease (CVD) in the future. It is unclear if prenatal vitamin D supplementation improves gestational CVH, especially in women at high risk for developing CVD. Our goal was to find out if vitamin D supplementation could protect against gestational CVH, including the women with GDM or obesity. DESIGN: We randomly assigned women with a serum 25(OH)D concentration < 75 nmol/L to receive 1600 IU/d (intervention group) or 400 IU/d (control group) of vitamin D3 for two months at 24-28 weeks' gestation. The primary outcome was gestational CVH marks (lipids, inflammatory cytokines, endothelial function). RESULTS: There were 1537 participants divided into the intervention (N = 766) and control groups (N = 771). No baseline differences existed among study groups in CVH markers. At the two-month visit, the intervention group's HDL-C levels (2.01 ± 0.39 VS 1.96 ± 0.39 mmol/L) were significantly higher than those of the control group, while the hs-CRP levels were significantly lower (3.28 ± 2.02 VS 3.64 ± 2.42 mg/L). Subgroup analysis found that HDL-C, TC, hs-CRP, E-Selectin, and SBP were improved in the intervention group among women with GDM or overweight/obesity, and the improvement was not found in women without GDM or overweight/obesity. Vitamin D supplementation significantly decreased the mean triglyceride-glucose index at the two-month visit in women with GDM. CONCLUSIONS: Vitamin D supplementation at mid-gestation might optimize the gestational CVH status for pregnant women, particularly the women with GDM or obesity, which is advantageous for later-life primary prevention of CVD. CLINICAL TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR2100051914, 10/9/2021, Prospective registered, https://www.chictr.org.cn/showproj.aspx?proj=134700 ).