Programmed surface platform orchestrates anti-bacterial ability and time-sequential bone healing for implant-associated infection.

Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag+) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

Hyperbranched Poly-l-Lysine Modified Titanium Surface With Enhanced Osseointegration, Bacteriostasis, and Anti-Inflammatory Properties for Implant Application: An Experimental In Vivo Study.

OBJECTIVES: This study aimed to explore multiple effects of hyperbranched poly-l-lysine (HBPL) titanium (Ti) surfaces on osseointegration, bacteriostasis, and anti-inflammation across three different animal models. METHODS: Ti surfaces were covalently modified with HBPL, with uncoated surfaces as controls. Characterization included scanning electron microscopy (SEM) and surface chemistry and elemental analysis (EDX). Ti and Ti-HBPL implants were placed in conventional canine edentulous sites, post-operative infection canine edentulous sites, and diabetic rat tibias. Implants from canine edentulous models were analyzed using micro-CT and histomorphometry to assess osseointegration at 8 weeks. Post-operative infection beagles were used to evaluate antibacterial efficacy through clinical parameters and bacterial cultures at 1 week. In diabetic rats, micro-CT and histomorphometry were performed at 8 weeks. RESULTS: HBPL was uniformly grafted on Ti-HBPL surfaces. Ti-HBPL surfaces showed higher bone volume/total volume (BV/TV, p < 0.001), bone-implant contact (BIC%, p < 0.001), and trabecular number (Tb.N, p < 0.01) in beagles. Besides, it displayed higher BIC% (p < 0.001) and bone area fraction occupancy (BAFO%, p < 0.01) in hard tissue sections. In an infected model, Ti-HBPL surfaces exhibited lower bleeding on probing (BOP, p < 0.001), and plaque index (DI, p < 0.01), with reduced bacterial colony formation (p < 0.001) compared to the control group. In diabetic rats, Ti-HBPL surfaces showed an increase in BV/TV (p < 0.01) and Tb.N (p < 0.001), downregulated TNF-α and IL-1ß (p < 0.01), and upregulated IL-10 (p < 0.01) and osteocalcin (OCN) expression (p < 0.01). CONCLUSIONS: HBPL-Ti surfaces demonstrated enhanced osseointegration, bacteriostasis, and anti-inflammatory effects in vivo.

The association between weight-adjusted waist index and sleep disorders in U.S. adults: results from NHANES 2005-2008.

The detrimental effects of obesity on sleep disorders have garnered a lot of interest. The weight-adjusted waist index (WWI) is a newly developed anthropometric index calculated in terms of weight and waist circumference. The body mass index has been employed to evaluate obesity in the majority of studies that connect obesity to sleep disorders. This study seeks to investigate the correlation between WWI and sleep disorders among adults in the United States. This cross-sectional study was part of the National Health and Nutrition Examination Survey and included adults aged >20 from 2005 to 2008. This study investigated the linear relationship between sleep disorders and WWI using weighted binary logistic regression models. Nonlinear relationships were characterized using smooth curve fitting and threshold effects analyses. After that, based on variables like gender, age, marital status, diabetes, hypertension, and smoking, subgroup analyses were performed. Our study included 9869 participants who were at least 20 years old. Higher WWI was linked to greater odds of sleep disorders prevalence, according to weighted binary logistic regression (odds ratio = 1.15; 95% confidence interval, 1.10, 1.20). In subgroup analyses based on age, marital status, diabetes, hypertension, and smoking, this connection remained robust. However, there were notable differences in this connection depending on gender. Furthermore, a nonlinear correlation with inflection points between WWI and sleep disorders was shown using smooth curve fitting. The nonlinear association between WWI and sleep disorders has an inflection point of 8.1 cm/√kg, as indicated by the threshold effect analyses. A higher WWI exposure may elevate the odds of sleep disorder prevalence, underscoring the importance of considering WWI in the prevention and management of sleep disorders.

Evaluation of 68Ga-FAPI PET/CT and 18F-FDG PET/CT for the diagnosis of recurrent colorectal cancers.

Objective: The present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (18F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs). Materials and Methods: Fifty-six patients (age: 18-80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18F-FDG PET/CT and 68Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student's t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities. Results: 68Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68Ga-FAPI PET/CT, respectively. Furthermore, 68Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18F-FDG PET/CT. For the same patient, 68Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18F-FDG PET/CT. Conclusion: 68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC.

Adipocyte-secreted PRELP promotes adipocyte differentiation and adipose tissue fibrosis by binding with p75NTR to activate FAK/MAPK signaling.

Adipocyte-secreted factors intricately regulate adipose tissue function, and the underlying molecular mechanisms are only partially understood. However, the function of PRELP, which is a key component of the extracellular matrix (ECM) in adipocytes, remains largely unknown. In this study, we demonstrate that PRELP was upregulated in both obese humans and mice, which exhibited a positive correlation with metabolic disorders. PRELP knockout could resist HFD-induced obesity and inhibit adipocyte differentiation. PRELP knockout improved glucose tolerance, insulin sensitivity and alleviated adipose tissue fibrosis. Mechanistically, PRELP was secreted into the ECM and bound to the extracellular domain of its receptor p75NTR in adipocytes, which further activated the FAK/MAPK (JNK, p38 MAPK, ERK1/2) signaling pathway, promoting adipocyte differentiation and exacerbating adipocyte fibrosis. Adipocyte PRELP plays a pivotal role in regulating obesity and adipose tissue fibrosis through an autocrine manner, and PRELP may be a therapeutic target for obesity and its related metabolic disorders.

Harnessing Deep Learning for Accurate Pathological Assessment of Brain Tumor Cell Types.

Primary diffuse central nervous system large B-cell lymphoma (CNS-pDLBCL) and high-grade glioma (HGG) often present similarly, clinically and on imaging, making differentiation challenging. This similarity can complicate pathologists' diagnostic efforts, yet accurately distinguishing between these conditions is crucial for guiding treatment decisions. This study leverages a deep learning model to classify brain tumor pathology images, addressing the common issue of limited medical imaging data. Instead of training a convolutional neural network (CNN) from scratch, we employ a pre-trained network for extracting deep features, which are then used by a support vector machine (SVM) for classification. Our evaluation shows that the Resnet50 (TL + SVM) model achieves a 97.4% accuracy, based on tenfold cross-validation on the test set. These results highlight the synergy between deep learning and traditional diagnostics, potentially setting a new standard for accuracy and efficiency in the pathological diagnosis of brain tumors.

IRX3 promotes adipose tissue browning and inhibits fibrosis in obesity-resistant mice.

Obesity is one of the threats to human health and survival. High fat diet (HFD)-induced obesity leads to adipose tissue fibrosis and a series of metabolic diseases. There are some people still thin under HFD, a phenomenon known as the "obesity resistance (OR) phenotype". It was found that Iroquois homeobox 3 (IRX3) is considered as a regulator in obesity, but the regulatory mechanism between OR and IRX3 is still unclear. In this study, we investigated OR on a HFD and the role of the IRX3 gene. Using mice, we observed that OR mice had lower body weights, reduced liver lipid synthesis, and increased white adipose tissue (WAT) lipolysis compared to obesity-prone (OP) mice. Additionally, OR mice exhibited spontaneous WAT browning and less fibrosis, correlating with higher Irx3 expression. Utilizing 3T3-L1 differentiated adipocytes, our study demonstrated that overexpression of Irx3 promoted thermogenesis-related gene expression and reduced adipocyte fibrosis. Therefore, Irx3 promotes WAT browning and inhibits fibrosis in OR mice. These results provide insight into the differences between obesity and OR, new perspectives on obesity treatment, and guidance for lessening adipose tissue fibrosis.

FXR, MRP-1 and SLC7A5: New Targets for the Treatment of Hepatocellular Carcinoma.

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

Epidermolysis Bullosa Pruriginosa treated with baricitinib: A case report.

INTRODUCTION: Epidermolysis Bullosa Pruriginosa (EBP) is a persistent, recurring disease that seriously affects quality of life. Fewer than 100 cases of EBP have been reported to date. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling, and inhibition of this pathway using Janus kinase (JAK) inhibitors might be a useful therapeutic strategy for these diseases. PATIENT CONCERNS: A male patient, 28 years of age, was admitted to our hospital because of recurrent papules, nodules, and intense itching on the trunk and extremities for 12 years. Repeated large and intense itching has seriously affected the patient normal life. DIAGNOSIS: The patient was diagnosed with EBP based on examination results. INTERVENTIONS: Oral baricitinib tablets (2 mg, once a day) + Oral desloratadine citrate disodium tablets (8.8 mg, once a day) combined with topical compound flumethasone ointment and Fucidin cream. OUTCOMES: The patient skin rashes had subsided and flattened remarkable, and his itching was markedly relieved. The visual analogue scale (VAS) itching score of the patient gradually declined from 8 to 9 points to 2 to 3 points. CONCLUSION: This study confirms that baricitinib is effective and feasible in treating EBP, especially in remarkable relieving itching, which rendered new ideas for therapeutic approaches for EBP in the future.

Altered leptin level in autism spectrum disorder and meta-analysis of adipokines.

BACKGROUND: Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis. METHODS: Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies. RESULTS: Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis. CONCLUSIONS: These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.

C-reactive protein-albumin-lymphocyte index as a feasible nutrition-immunity-inflammation marker of the outcome of all-cause and cardiovascular mortality in elderly.

BACKGROUND & AIMS: The imbalance of nutrition-immunity-inflammation status might be associated with the mortality risk in the elderly. This study aimed to assess the relationship between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index and all-cause and cardiovascular disease (CVD) mortality in the elderly. METHODS: The data from records of older adults (≥ 60 years) were derived from 1999 to 2010 and 2015-2018 National Health and Nutrition Examination Survey. Weighted Cox proportional hazard regression was used to analyze the relationship between CALLY and all-cause mortality and CVD mortality in three different models, and the linear trend was analyzed. A restricted cubic spline model was used to evaluate the nonlinear dose-response relationship and determine the critical threshold of CALLY to divide the population into two groups. Kaplan-Meier analysis and log-rank test were used to evaluate the cumulative survival rates of different groups. Subgroup analyses and sensitivity analyses were performed to ensure robustness. RESULTS: Compared to the first quartile of natural log-transformation (ln) CALLY, the highest quartile of ln CALLY was negatively correlated with the risk of all-cause mortality (HR = 0.67, 95% CI: 0.56-0.79. P < 0.05) and CVD mortality (HR = 0.65, 95% CI: 0.47-0.89. P < 0.05) in model 3. Ln CALLY was linear dose-response correlated with mortality. We determined that the critical threshold for ln CALLY in elderly was 1.00. Elderly with higher ln CALLY (≥ 1.00) had significantly increased survival rates (P < 0.05). CONCLUSION: CALLY showed a significant negative linear association with the risk of all-cause mortality and CVD mortality, and higher CALLY was beneficial to the survival outcomes of the elderly.

Nanotechnology for tau pathology in Alzheimer's disease.

Tau protein aggregation is a defining characteristic of Alzheimer's disease (AD), leading to the formation of neurofibrillary tangles that disrupt neural communication and ultimately result in cognitive decline. Nanotechnology presents novel strategies for both diagnosing and treating Alzheimer's disease. Nanotechnology. It has become a revolutionary tool in the fight against Alzheimer's disease, particularly in addressing the pathological accumulation of tau protein. This review explores the relationship between tau-related neurophysiology and the utilization of nanotechnology for AD treatment, focusing on the application of nanomaterials to regulate tau phosphorylation, hinder tau aggregation and propagation, stabilize microtubules, eliminate pathological tau and emphasize the potential of nanotechnology in developing personalized therapies and monitoring treatment responses in AD patients. This review combines tau-related neurophysiology with nanotechnology to provide new insights for further understanding and treating Alzheimer's disease.

Functionally Designed Nanovaccines against SARS-CoV-2 and Its Variants.

COVID-19, generated by SARS-CoV-2, has significantly affected healthcare systems worldwide. The epidemic has highlighted the urgent need for vaccine development. Besides the conventional vaccination models, which include live-attenuated, recombinant protein, and inactivated vaccines, nanovaccines present a distinct opportunity to progress vaccine research and offer convenient alternatives. This review highlights the many widely used nanoparticle vaccine vectors, outlines their benefits and drawbacks, and examines recent developments in nanoparticle vaccines to prevent SARS-CoV-2. It also offers a thorough overview of the many advantages of nanoparticle vaccines, including an enhanced host immune response, multivalent antigen delivery, and efficient drug delivery. The main objective is to provide a reference for the development of innovative antiviral vaccines.

Adipocyte-specific FAK deletion promotes pancreatic ß-cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus.

BACKGROUND: White adipose tissue (WAT) has a key role in maintaining energy balance throughout the body, and their dysfunction take part in the regulation of diabetes mellitus. However, the internal regulatory mechanisms underlying are still unknown. METHODS AND RESULTS: We generated adipocyte-specific FAK KO (FAK-AKO) mice and investigated their phenotype. The cascade of adipocyte, macrophage in adipocyte tissues, and pancreatic ß-cells were proposed in FAK-AKO mice and validated by cell line studies using 3T3-L1, Raw264.7 and Min6. The FAK-AKO mice exhibited glucose intolerance, reduced adipose tissue mass and increased apoptosis, lipolysis and inflammatory response in adipose tissue. We further demonstrate that adipocyte FAK deletion increases ß cell apoptosis and inflammatory infiltrates into islets, which is potentiated if mice were treated with STZ. In the STZ-induced diabetes model, FAK AKO mice exhibit less serum insulin content and pancreatic ß cell area. Moreover, serum pro-inflammatory factors increased and insulin levels decreased after glucose stimulation in FAK AKO mice. In a parallel vitro experiment, knockdown or inhibition of FAK during differentiation also increased apoptosis, lipolysis and inflammatory in 3T3-L1 adipocytes, whereas the opposite was observed upon overexpression of FAK. Moreover, coculturing LPS-treated RAW264.7 macrophages with knockdown FAK of 3T3-L1 adipocytes increased macrophage pro-inflammatory response. Furthermore, conditioned medium from above stimulated Min6 cells apoptosis (with or without STZ), whereas the opposite was observed upon overexpression of FAK. Mechanistically, FAK protein interact with TRAF6 in adipocytes and knockdown or inhibition of FAK activated TRAF6/TAK1/NF-κB signaling, which exacerbates inflammation of adipocytes themselves. CONCLUSION: Adipocyte FAK deletion promotes both adipocyte apoptosis and adipose tissue inflammation. Pro-inflammatory factors released by the FAK-null adipose tissue further trigger apoptosis in pancreatic islets induced by the administration of STZ, thereby exacerbating the diabetes mellitus. This study reveals a link between FAK-mediated adipose inflammation and diabetes mellitus, a mechanism that has not been previously recognized.

A visual circuit related to the parabrachial nucleus for the antipruritic effects of bright light treatment.

In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light treatment, the circuit mechanisms underlying the effects of light on itch-related behaviors remain poorly understood. In this study, we demonstrate that bright light treatment reduces itch-related behaviors in mice through a visual circuit related to the lateral parabrachial nucleus (LPBN). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which subsequently inhibit CaMKIIα+ neurons in the LPBN. Activation of both the vLGN/IGL-projecting RGCs and the vLGN/IGL-to-LPBN projections is sufficient to reduce itch-related behaviors induced by various pruritogens. Importantly, we demonstrate that the antipruritic effects of bright light treatment rely on the activation of the retina-vLGN/IGL-LPBN pathway. Collectively, our findings elucidate a visual circuit related to the LPBN that underlies the antipruritic effects of bright light treatment.

A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes: The EARLY Randomized Clinical Trial.

Importance: An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) could provide additional benefits to patients with type 2 diabetes. Objective: To evaluate the effect of the 5:2 MR on glycemic control among patients with early type 2 diabetes compared with metformin and empagliflozin. Design, Setting, and Participants: The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized, open-label, active parallel-controlled clinical trial conducted between November 13, 2020, and December 29, 2022, in 9 centers across China. A total of 509 eligible patients underwent screening, out of which 405 were randomly assigned to 3 groups and included in the intention-to-treat analysis. Interventions: Patients were randomly allocated in a 1:1:1 ratio to receive either metformin, empagliflozin, or 5:2 MR. The treatment was 16 weeks, with an 8-week follow-up. Main Outcomes and Measures: The primary end point was the change in hemoglobin A1c (HbA1c) level from baseline to 16 weeks. Secondary end points included changes in body weight, anthropometric measurements, and biochemical parameters. Results: Of the 405 randomized participants (265 men [65.4%]; mean [SD] age, 45.5 [11.0] years; mean [SD] body mass index, 29.5 [4.1]; and mean [SD] HbA1c level, 7.9% [0.6%]), 332 completed the 16-week treatment. From baseline to week 16, participants in the 5:2 MR group showed the greatest reduction in HbA1c (least-squares mean [LSM], -1.9% [SE, 0.2%]), significantly greater than patients receiving metformin (LSM, -1.6% [SE, 0.2%]; adjusted LSM difference, -0.3% [95% CI, -0.4% to -0.1%]) and empagliflozin (LSM, -1.5% [SE, 0.2%]; adjusted LSM difference, -0.4% [95% CI, -0.6% to -0.2%]). At week 16, the mean weight loss in the 5:2 MR group (LSM, -9.7 kg [SE, 2.2 kg]) was greater than that in the metformin group (LSM, -5.5 kg [SE, 2.3 kg]) and empagliflozin group (LSM, -5.8 kg [SE, 2.3 kg]). Conclusions and Relevance: This randomized clinical trial of Chinese adults with overweight or obesity and with early type 2 diabetes found that 5:2 MR could improve glycemic outcomes and weight loss in the short term compared with metformin or empagliflozin, making it a promising initial intervention and early management for type 2 diabetes. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000040656.

The effects of vitamin D supplementation on serum lipid profiles in people with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

Introduction: People with type 2 diabetes (T2D) are highly susceptible to the development of cardiovascular diseases. Previous studies have suggested that the application of vitamin D may offer potential benefits in improving lipid profiles, but these effects remain controversial. Methods: This systematic review and meta-analysis focused on the effects of vitamin D supplementation on serum lipid profiles in people with T2D. Randomized controlled trials (RCTs) assessing the effects of vitamin D supplementation on lipid profiles and published before September 19th, 2023, were identified in PubMed, Embase, and Cochrane Library. This review protocol was registered in the PROSPERO (CRD42023461136). The random-effects model was employed to estimate unstandardized mean differences (MD) and 95% confidence intervals (CIs). The quality of studies was assessed by the Cochrane Risk of Bias tool 2. Results: Overall, 20 RCTs involving 1711 participants were included. Results indicated that vitamin D supplementation significantly improves serum high-density lipoprotein (HDL) (MD: 1.63 mg/dL, 95% CI: 0.19 to 3.08, P = 0.03), and triglyceride (TG) levels (MD: -8.56 mg/dL, 95% CI: -15.23 to -1.89, P = 0.01). However, vitamin D supplementation failed to improve low-density lipoprotein (LDL) levels and total cholesterol (TC) levels. Subgroup analyses and meta-regressions suggested that higher doses of vitamin D supplementation and shorter duration of intervention were more likely to have favorable effects on lipid profiles. Moreover, participants with lower baseline BMI and higher serum 25-hydroxy vitamin D levels exhibited greater improvements in lipid profiles following vitamin D supplementation. Conclusions: This meta-analysis highlighted the effects of vitamin D supplementation on improving serum HDL and TG levels while not exhibiting significant improvements in LDL and TC levels. Further long-term and high-quality studies are still needed to draw more precise conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461136.

Effects of Silybum marianum, Pueraria lobate, combined with Salvia miltiorrhiza tablets on non-alcoholic fatty liver disease in adults: A triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND & AIMS: Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults. METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism. RESULTS: A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn't reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058). CONCLUSION: SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.

Novel insights on room temperature-induced cellulose dissolution mechanism via ZnCl2 aqueous solution: Migration, penetration, interaction, and dispersion.

The unique molecular structure of cellulose makes it challenging to dissolve at room temperature (R.T.), and the dissolution mechanism remains unclear. In this study, we employed ZnCl2 aqueous solution for cellulose dissolution at R.T., proposing a novel four-stage dissolution mechanism. The efficient dissolution of cellulose in ZnCl2 aqueous solution at R.T. involves four indispensable stages: rapid migration of hydrated Zn2+ ions towards cellulose, sufficient penetration between cellulose sheets, strong interaction with cellulose hydroxyl groups, and effective dispersion of separated cellulose chains. The proposed four-stage dissolution mechanism was validated through theoretical calculations and experimental evidence. The hydrated Zn2+ ions in ZnCl2 + 3.5H2O solvent exhibited ideal migration, penetration, interaction, and dispersion abilities, resulting in efficient cellulose dissolution at R.T. Moreover, only slight degradation of cellulose occurred in ZnCl2 + 3.5H2O at R.T. Consequently, the regenerated cellulose materials obtained from ZnCl2 + 3.5H2O (R.T.) exhibited better mechanical properties. Notably, the solvent recovery rate reached about 95 % based on previous usage during five cycles. The solvent is outstanding for its green, low-cost, efficiency, simplicity, R.T. conditions and recyclability. This work contributes to a better understanding of the cellulose dissolution mechanisms within inorganic salt solvents at R.T., thereby guiding future development efforts towards greener and more efficient cellulosic solvents.