[Clinical features and genetic analysis of five children with epilepsies due to variants of SCN8A gene].

OBJECTIVE: To explore the clinical and genetic characteristics of five children with epilepsies due to variants of SCN8A gene. METHODS: Clinical data of five children (four males and one female) admitted to Linyi People's Hospital due to hereditary epilepsies between August 2015 and August 2022 were collected. Whole exome sequencing was carried out for these children, and candidate variants were verified by Sanger sequencing. RESULTS: All of the five children were found to harbor variants of the SCN8A gene. Case 1, who had benign familial infantile epilepsy, inherited a known pathogenic c.4840A>G variant from his father with similar symptoms. Cases 2 to 4 had presented with intermediate epilepsy. Among these, case 2 has harbored a de novo c.3967G>A variant which was rated as pathogenic (PS1+PS2+PM1+PM2_Supporting+PP3) based on the guidelines from the American College of Medical Genetics and Genomics. Cases 3 and 4 were found to respectively harbor a de novo c.415A>T and a c.4697C>T variant, which were both rated as likely pathogenic (PS2+PM1+PM2_Supporting+PP3). Case 5, who had early-onset infantile epileptic encephalopathy transformed into Lennox Gastaut-like syndrome, has harbored a de novo c.5615G>A variant, which was known to be pathogenic. The children had their age of onset ranging from 2 to 14 months, and all had focal seizures and generalized tonic clonic seizures. Four children (cases 1, 2, 3 and 5) had cluster seizures, four (cases 1 to 4) had become seizure-free after single or dual treatment and showed normal growth and development, whilst case 5 was drug-resistant and showed severe developmental retardation. CONCLUSION: The five children had new features such as cluster seizures, occasional benign seizures in adulthood, and intermediate epilepsy which are prone to relapse after discontinuation of medication, which may be attributed to the pathogenic variants of the SCN8A gene.

Clinical phenotype and genetic characteristics of SZT2 related diseases: A case report and literature review.

PURPOSE: Seizure threshold 2 protein homolog gene (SZT2, MIM: 615463) related diseases are extremely rare autosomal recessive disorders with a wide spectrum of clinical phenotypes ranging from mild intellectual impairment to severe developmental epileptic encephalopathy (DEE). Most SZT2 related diseases are accompanied by craniofacial malformation and corpus callosum malformation. This study attempts to analyze and summarize the clinical phenotype and genetic characteristics of SZT2 related diseases, providing a basis for early diagnosis, treatment, and prognosis. METHOD: We analyzed the clinical characteristics of a Chinese child with pathogenic variants of SZT2. We also performed whole-exome sequencing (WES) on the patient. In addition, we conducted a literature review of previously reported patients with pathogenic mutations in the SZT2 gene. RESULT: The proband was a boy aged 1 year and 9 months with severe global developmental delay, transient drug-controlled focal epilepsy, cluster epilepsy, autism spectrum disorder, craniofacial deformity, hypotonia, focal EEG discharge, corpus callosum malformation, and persistent cavum septum pellucidum. WES revealed that the patient carried the SZT2 gene c.7584dupA and c.6302A>C complex heterozygous variants; the former being Likely Pathogenic (LP) and the latter Uncertain Significance (VUS) according to ACMG classification guidelines. According to our literature review, 43 cases of SZT2 related diseases have been reported so far; these include 15 cases with homozygous variations and 28 cases with complex heterozygous variations. A total of 57 types of variation were found, including 47 genetic variants, 2 de novo variants, and 8 unknown genetic modes. In addition, 2 high-frequency variants were found (c.5949_5951delTGT and c.6553C>T). The main clinical manifestations of the 40 patients were global developmental delay (GDD) of varying degrees (38/40, 95.00 %), seizures (36/40, 90.00 %), cranial deformity (27/40, 67.50 %), facial deformity (22/40, 55.00 %), hypotonia (22/40, 55.00 %), abnormal interseizure EEG discharge (26/40, 65.00 %), slow background activity (20/40, 50.00 %), corpus callosum deformity (18/40, 45.00 %). There was also one case of sudden unexpected death in epilepsy (SUDEP) and 3 cases of death from infection. In addition, three fetuses with the same variant had hydrocephalus and encephalocele. CONCLUSION: The compound heterozygous mutation of c.7584dupA and c.6302A>C in the SZT2 gene is the genetic etiology of this patient, expanding the mutation spectrum of SZT2 related diseases. Early genetic testing is the best choice for clear diagnosis, treatment, and prognosis.

Cell and rat serum, urine and tissue metabolomics analysis elucidates the key pathway changes associated with chronic nephropathy and reveals the mechanism of action of rhein.

BACKGROUND: Rhein can significantly delay the progression of chronic nephropathy. However, its mechanism of action has not been adequately elaborated, which hinders its extensive clinical application. In this work, the effects of rhein on models of TGF-ß-induced NRK-49F cellular fibrosis and rat renal ischemia-reperfusion fibrosis were evaluated using metabolomics and western blotting. METHODS: The metabolic profiles of NRK-49F cells and rat urine, serum, and kidney tissues in the control, model, and rhein groups were investigated using UPLC-QTOF-MS. The levels of p-P65, p-IKK, p-AKT, p-P38, p-JNK and AP-1 in NRK-49F cells were measured using western blotting and immunofluorescence methods. Molecular docking and network pharmacology methods were employed to explore the relationship between the potential targets of rhein and key proteins in the NF-κB and MAPK signaling pathways. RESULTS: Various potential metabolites, including sphingolipids, ceramides, phosphatidylcholine, and lysophosphatidylcholine,14-hydroxy-E4-neuroprostane E, and 5-HPETE, were present in the cell, tissue, urine, and serum samples; however, few metabolites matches exactly among the four type of biological samples. These differential metabolites can effectively differentiated between the control, model, and rhein groups. Pathway enrichment analysis of differential metabolites unveiled that sphingolipid metabolism, arachidonic acid metabolism, and glycerophospholipid metabolism were closely related to nephropathy. Phosphorylation levels of AKT, IKK, P65 and AP-1 in NRK-49F cells was reduced by rhein treatment. Network pharmacology and molecular docking showed that the potential targets of rhein might regulated the expression of MAPK and AKT in the NF-κB and MAPK signaling pathways. CONCLUSION: In brief, rhein might delays the progression of chronic nephropathy via the metabolic pathways, NF-κB and MAPKs signaling pathways, which provides the foundation for its development and clinical application.

Heart failure with preserved ejection fraction in haemodialysis patients: prevalence, diagnosis, risk factors, prognosis.

AIMS: Heart failure (HF) is a common complication and the leading cause of mortality in maintenance haemodialysis (MHD) patients. Few studies have investigated heart failure with preserved ejection fraction (HFpEF), which is known to affect a majority of patients. The objective of this study is to explore the prevalence, clinical profiles, diagnosis, risk factors and prognosis of MHD patients with HFpEF. METHODS AND RESULTS: Four hundred thirty-nine patients haemodialyzsed for over 3 months were enrolled in the study and evaluated for HF according to the European Society of Cardiology guidelines. Clinical and laboratory parameters were recorded at baseline. The median follow-up of the study was 22.5 months. A total of 111 (25.3%) MHD patients were diagnosed with HF, while 94 (84.7%) of the HF patients were classified into HFpEF. The cut-off value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 4922.5 pg/mL for predicting HFpEF (sensitivity 0.840, specificity 0.723, AUC 0.866) in MHD patients. Age, diabetes mellitus, coronary artery disease and serum phosphorus were independent risk factors for the incidence of HFpEF in MHD patients while normal urine volume, haemoglobin, serum iron and serum sodium were protective factors. MHD patients with HFpEF had a higher risk of all-cause mortality than those without HF (hazard ratio 2.47, 95% confidence interval 1.55-3.91, P < 0.0001). CONCLUSIONS: The majority of MHD patients with HF were categorized into HFpEF, with a poor long-term survival rate. NT-proBNP beyond 4922.5 pg/mL performed well in the prediction of HFpEF in MHD patients.

Validation of the children international IgA nephropathy prediction tool based on data in Southwest China.

Background: Immunoglobulin A nephropathy (IgAN) is one of the most common kidney diseases leading to renal injury. Of pediatric cases, 25%-30% progress into end-stage kidney disease (ESKD) in 20-25 years. Therefore, predicting and intervening in IgAN at an early stage is crucial. The purpose of this study was to validate the availability of an international predictive tool for childhood IgAN in a cohort of children with IgAN treated at a regional medical centre. Methods: An external validation cohort of children with IgAN from medical centers in Southwest China was formed to validate the predictive performance of the two full models with and without race differences by comparing four measures: area under the curve (AUC), the regression coefficient of linear prediction (PI), survival analysis curves for different risk groups, and R2D. Results: A total of 210 Chinese children, including 129 males, with an overall mean age of 9.43 ± 2.71 years, were incorporated from this regional medical center. In total, 11.43% (24/210) of patients achieved an outcome with a GFR decrease of more than 30% or reached ESKD. The AUC of the full model with race was 0.685 (95% CI: 0.570-0.800) and the AUC of the full model without race was 0.640 (95% CI: 0.517-0.764). The PI of the full model with race and without race was 0.816 (SE = 0.006, P < 0.001) and 0.751 (SE = 0.005, P < 0.001), respectively. The results of the survival curve analysis suggested the two models could not well distinguish between the low-risk and high-risk groups (P = 0.359 and P = 0.452), respectively, no matter the race difference. The evaluation of model fit for the full model with race was 66.5% and without race was 56.2%. Conclusions: The international IgAN prediction tool has risk factors chosen based on adult data, and the validation cohort did not fully align with the derivation cohort in terms of demographic characteristics, clinical baseline levels, and pathological presentation, so the tool may not be highly applicable to children. We need to build IgAN prediction models that are more applicable to Chinese children based on their particular data.

Atomic Visualization of the 3D Charge Density Wave Stacking in 1T-TaS2 by Cryogenic Transmission Electron Microscopy.

Charge density waves (CDWs) in 1T-TaS2 maintain 2D ordering by forming periodic in-plane star-of-David (SOD) patterns, while they also intertwined with orbital order in the c axis. Recent theoretical calculations and surface measurements have explored 3D CDW configurations, but interlayer intertwining of a 2D CDW order remains elusive. Here, we investigate the in- and out-of-plane ordering of the commensurate CDW superstructure in a 1T-TaS2 thin flake in real space, using aberration-corrected cryogenic transmission electronic microscopy (cryo-TEM) in low-dose mode, far below the threshold dose for an electron-induced CDW phase transition. By scrutinizing the phase intensity variation of modulated Ta atoms, we visualize the penetrative 3D CDW stacking structure, revealing an intertwining multidomain structure with three types of vertical CDW stacking configurations. Our results provide microstructural evidence for the coexistence of local Mott insulation and metal phases and offer a paradigm for studying the CDW structure and correlation order in condensed-matter physics using cryo-TEM.

Genetically engineered PD-1 displaying nanovesicles for synergistic checkpoint blockades and chemo-metabolic therapy against non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) remains the most frequently diagnosed lung cancer and the leading cause of cancer-related mortality worldwide. PD-1/PD-L1 axis inhibitors have changed the treatment paradigm for various cancer types, including NSCLC. However, success of these inhibitors in lung cancer clinic is severely limited by their inability to inhibit the PD-1/PD-L1 signaling axis due to heavy glycosylation and heterogeneity expression of PD-L1 in NSCLC tumor tissue. Taking advantage of the facts that tumor cell derived nanovesicles could efficiently accumulate in the homotypic tumor sites due to their innate targeting abilities and that specific and high affinity existed between PD-1 and PD-L1, we developed NSCLC targeting biomimetic nanovesicles (NV) cargos from genetically engineered NSCLC cell lines that overexpressed PD-1 (P-NV). We showed that P-NVs efficiently bound NSCLC cells in vitro and targeted tumor nodules in vivo. We further loaded P-NVs with 2-deoxy-D-glucose (2-DG) and doxorubicin (DOX), and found that these drugs co-loaded P-NVs efficiently shrank lung cancers in mouse models for both allograft and autochthonous tumor. Mechanistically, drug-loaded P-NVs efficiently caused cytotoxicity to tumor cells and simultaneously activated anti-tumor immunity function of tumor-infiltrating T cells. Our data therefore strongly argue that 2-DG and DOX co-loaded, PD-1-displaying nanovesicles is a highly promising therapy for treatment of NSCLC in clinic. STATEMENT OF SIGNIFICANCE: Lung cancer cells overexpressing PD-1 are developed for preparing nanoparticles (P-NV). PD-1s displayed on NVs enhance their homologous targeting abilities to tumor cells expressing PD-L1s. Chemotherapeutics such as DOX and 2-DG, are packaged in such nanovesicles (PDG-NV). These nanovesicles efficiently delivered chemotherapeutics to tumor nodules specifically. The synergy between DOX and 2-DG is observed in inhibiting lung cancer cells in vitro and in vivo. Importantly, 2-DG causes deglycosylation and downregulation of PD-L1 on tumor cells while PD-1 displayed on nanovesicles' membrane blocks PD-L1 on tumor cells. 2-DG loaded nanoparticles thus activate anti-tumor activities of T cells in the tumor microenvironment. Our work thus highlights the promising antitumor activity of PDG-NVs, which warrants further clinical evaluation.

Effects of dietary restriction on genome stability are sex and feeding regimen dependent.

Preserving genome stability is essential to prevent aging and cancer. Dietary restriction (DR) is the most reproducible non-pharmacological way to improve health and extend lifespan in various species. Whether DR helps to preserve genome stability and whether this effect is altered by experimental variables remain unclear. Moreover, DR research relies heavily on experimental animals, making the development of reliable in vitro mimetics of great interest. Therefore, we tested the effects of sex and feeding regimen (time-restricted eating, alternate day fasting and calorie restriction) on genome stability in CF-1 mice and whether these effects can be recapitulated by cell culture paradigms. Here, we show that calorie restriction significantly decreases the spontaneous micronuclei (MN), a biomarker of genome instability, in bone marrow cells of females instead of males. Alternate day fasting significantly decreases cisplatin-induced MN in females instead of males. Unexpectedly, daily time-restricted eating significantly exacerbates cisplatin-induced MN in males but not in females. Additionally, we design several culture paradigms that are able to faithfully recapitulate the key effects of these DR regimens on genome stability. In particular, 30% reduction of serum, a mimetic of calorie restriction, exhibits a strong ability to decrease spontaneous and cisplatin-induced MN in immortalized human umbilical vein endothelial cells. We conclude that the effects of different DR regimens on genome stability are not universal and females from each diet regimen sustain a more stable genome than males. Our results provide novel insight into the understanding of how DR influences genome stability in a sex and regimen dependent way, and suggest that our in vitro DR mimetics could be adopted to study the underlying molecular mechanisms.

Betamethasone-loaded dissolvable microneedle patch for oral ulcer treatment.

Oral inflammatory disease (OID) is among the most common oral lesions, affecting people's quality of life and even leading to oral cancer. Oral ulcers are the most common OID. However, the pain and fear caused by the localized injection of hormones hinder the clinical treatment of oral ulcers. To address this problem, soluble hyaluronic acid (HA) microneedle patches (BSP-BDP@HAMN) containing betamethasone 21-phosphate sodium (BSP) and betamethasone 17,21-dipropionate (BDP) were fabricated for potential application in oral ulcers. BSP-BDP@HAMNs had the sufficient mechanical strength to penetrate the rat tongue abdomen mucosa with an insertion depth of approximately 207 ± 3 µm. The rapidly solubilized HA microneedle carrier released BSP and BDP into the ulcer base within 3 min of entering the mucosa. Cellular assays have shown that BDP@HAMNs have wound healing-promoting and anti-inflammatory effects. Compared with topical injections and creams, BSP-BDP@HAMNs not only penetrated the ulcer surface painlessly but also worked deep in the ulcer for a long time. In conclusion, the proposed BSP-BDP@HAMN patch can improve the comfort and efficacy of oral ulcer treatment, thus providing a new prospect for oral ulcer treatment.

The right microbe-associated molecular patterns for effective recognition by plants.

Plants are constantly exposed to diverse microbes and thus develop a sophisticated perceive system to distinguish non-self from self and identify non-self as friends or foes. Plants can detect microbes in apoplast via recognition of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) on the cell surface to activate appropriate signaling in response to microbes. MAMPs are highly conserved but essential molecules of microbes and often buried in microbes' complex structure. Mature MAMPs are released from microbes by invasion-induced hydrolytic enzymes in apoplast and accumulate in proximity of plasma membrane-localized PRRs to be perceived as ligands to activate downstream signaling. In response, microbes developed strategies to counteract these processing. Here, we review how the form, the concentration, and the size of mature MAMPs affect the PRR-mediated immune signaling. In particular, we describe some potential applications and explore potential open questions in the fields.

Timing selection for loosened tooth fixation based on degree of alveolar bone resorption: a finite element analysis.

OBJECTIVE: This study aimed to evaluate timing of fixation to retard bone absorption using finite element analysis(FEA). METHODS: Volunteer CT images were used to construct four models of mandibles with varying degrees of alveolar bone resorption. By simulating occlusal force loading, biomechanical analysis was made on the periodontal membrane, tooth root and surrounding bone (both cancellous and cortical) of mandibular dentition. RESULTS: The von Mises stress value of the periodontal structures was positively related with the degree of alveolar bone resorption, and the von Mises stress at the interface between the periodontal membrane and tooth root was increased significantly in moderate to severe periodontitis models. The von Mises stress at the interface between the periodontal cortical bone and cancellous bone was increased significantly in the severe periodontitis model. And the von Mises stress value with oblique loading showed significantly higher than vertical loading. CONCLUSION: Teeth with moderate to severe periodontitis, loosened tooth fixation can be used to retard bone absorption.

Pathogenesis and Therapeutic Strategies Related to Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), one of the most common types of chronic liver disease, is strongly correlated with obesity, insulin resistance, metabolic syndrome, and genetic components. The pathological progression of NAFLD, consisting of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and liver cirrhosis, is characterized by a broad spectrum of clinical phenotypes. Although patients with mild NAFL are considered to show no obvious clinical symptoms, patients with long-term NAFL may culminate in NASH and further liver fibrosis. Even though various drugs are able to improve NAFLD, there are no FDA-approved medications that directly treat NAFLD. In this paper, the pathogenesis of NAFLD, the potential therapeutic targets, and their underlying mechanisms of action were reviewed.

A network pharmacology-based study on the mechanism of astragaloside IV alleviating renal fibrosis through the AKT1/GSK-3ß pathway.

ETHNOPHARMACOLOGICAL REVELVANCE: Astragaloside IV, a glycoside derived from Astragalus membranaceus, has anti-renal fibrosis effects. However, its mechanism of action has not yet been fully elucidated. AIM OF THE STUDY: The purpose of this study was to investigate the anti-fibrotic effect of AS-IV and to clarify its underlying mechanism. MATERIALS AND METHODS: The network pharmacology method, molecular docking and surface plasmon resonance (SPR) was used to identify potential targets and pathways of AS-IV. A unilateral ischemia-reperfusion injury (UIRI) animal model, as well as TGF-ß1-induced rat renal tubular epithelial cells (NRK-52E) and renal fibroblasts (NRK-49F) were used to investigate and validate the anti-fibrotic activity and pharmacological mechanism of AS-IV. Network pharmacology was performed to construct a drug-target-pathway network. The anti-fibrosis effect of AS-IV was determined using hematoxylin-eosin (H&E) and MASSON staining, as well as immunostaining methods. qRT-PCR and western blotting were used to elucidate and validate the mechanism of AS-IV. RESULTS: Network pharmacology revealed that the PI3K/AKT pathway is an important pathway in AS-IV. AS-IV inhibited the expression of α-SMA, collagen I, and fibronectin in NRK-52E, NRK-49F, and UIRI rats, and reduced serum creatinine and blood urea nitrogen levels in UIRI rats. AS-IV inhibited AKT phosphorylation, blocked GSK-3ß phosphorylation, and restored GSK-3ß activity, which contributed to the degradation of ß-catenin, thereby preventing epithelial-mesenchymal transition (EMT). CONCLUSION: Astragaloside IV alleviated renal fibrosis through the AKT1/GSK-3ß pathway. In addition, our findings indicate that the network pharmacology method is a powerful tool for exploring the pharmacological mechanisms of drugs.

An integrated network pharmacology and cell metabolomics approach to reveal the role of rhein, a novel PPARα agonist, against renal fibrosis by activating the PPARα-CPT1A axis.

BACKGROUND: Rhein, an anthraquinone compound, displays extensive antifibrotic effects; however, its potential mechanisms are not fully understood. In this study, we explored the underlying molecular mechanism of action of rhein. METHOD: An integrated network pharmacology and cell metabolomics approach was developed based on network pharmacology and bioinformatics method, and then successfully applied to speculate the potential targets of rhein and construct a rhein-target-metabolic enzyme-metabolite network. Thereafter, the antifibrotic mechanism of rhein was validated in TGF-ß- and oleic acid- induced HK-2 and NRK-52E cells in vitro as well as a unilateral ischemia-reperfusion injury Sprague-Dawley rat model. RESULTS: Based on the construction of the rhein-target-metabolic enzyme-metabolite network, we found that rhein played an antifibrotic role through the PPAR-α-CPT1A-l-palmitoyl-carnitine axis. In vitro experiments demonstrated that rhein effectively activated the expression of PPARα and its downstream proteins (CPT1A and ACOX1) to alleviate lipid accumulation and fibrosis development. In vivo experiments indicated that rhein attenuated renal fibrosis mainly by activating the fatty acid oxidation pathway and improving lipid metabolism. CONCLUSION: Taken together, our findings reveal that rhein is a novel agonist of PPARα, which contributes to its renoprotection through the regulation of the PPARα-CPT1A axis. Moreover, our study provides a novel insight into an integrated network pharmacology-metabolomics strategy for uncovering the pharmacological mechanisms of drugs from the system perspective.

Lidocaine-Loaded Hyaluronic Acid Adhesive Microneedle Patch for Oral Mucosal Topical Anesthesia.

The pain and fear caused by direct local injection of anesthetic or the poor experience with surface anesthetic cream increase the difficulty of clinical treatment for oral diseases. To address this problem, a hyaluronic acid microneedle patch (Li-HAMNs) that consists of fast-dissolving lidocaine hydrochloride (LDC)-loaded tips and a wet-adhesive backing layer made of polyvinyl alcohol (PVA)/carboxymethylcellulose sodium (CMC-Na) was fabricated to explore its potential use in dental topical anesthesia. Li-HAMNs could puncture the stratum corneum with an insertion depth of about 279 µm in the isolated porcine oral mucosal. The fast-dissolving tips could release LDC to improve the patients' convenience and compliance. Importantly, the backing layer, which has good adhesion ability and water-absorbing properties, could surmount the contraction and extension of oral masticatory muscles and the saliva scour. In the tail flick test, the topical anesthesia efficacy of the Li-HAMNs group was much better than clinical lidocaine cream (EMLA cream, LDC, 1.2 mg) in spite of a relatively lower LDC dose with Li-HAMNs (LDC, 0.5 mg). It is believed that the proposed adhesive microneedle patch could enhance transmucosal delivery of anesthetics and thus open a new chapter in the painless treatment of oral diseases.

Microneedle Array Patch Made of Kangfuxin/Chitosan/Fucoidan Complex Enables Full-Thickness Wound Healing.

Skin wound caused by external injury is usually difficult to be cured by conventional topical administration because of its poor drug diffusion across the stratum corneum. It has been recognized that stratum corneum is the major obstacle for transdermal drug delivery. To address this issue, microneedles (MNs) have been developed to penetrate the stratum corneum of the skin and then form micron-sized pores between the epidermis and the dermis layers. As such, biomacromolecule drugs and/or insoluble drug molecules can be allowed for effective transdermal penetration. A multifunctional microneedle array patch that can avoid wound infection and promote tissue remolding has important value for wound healing. Among others, marine polysaccharides have attracted much attention in multifarious biomedical applications due to their excellent (bio)physical and chemical properties. Herein, we developed a microneedle array patch using a blend of kangfuxin (KFX), chitosan (CS), and fucoidan (FD), named KCFMN, for accelerating full-thickness wound healing. The traditional Chinese medicine KFX extracted from Periplaneta americana (PA) has effective bio-functions in promoting wound healing. The macro-/micro-morphology and (bio)physicochemical properties of such composite microneedles were also studied. We showed that the KCFMN patch displayed noticeable antibacterial properties and good cytocompatibility. In particular, the KCFMN patch significantly accelerated the wound healing development in a full-thickness wound in rats by improving the epithelial thickness and collagen deposition. Thus, this versatile KCFMN patch has great prospects as a dressing for full-thickness wound healing.

Rubber Seed Oil-Based UV-Curable Polyurethane Acrylate Resins for Digital Light Processing (DLP) 3D Printing.

Novel UV-curable polyurethane acrylate (PUA) resins were developed from rubber seed oil (RSO). Firstly, hydroxylated rubber seed oil (HRSO) was prepared via an alcoholysis reaction of RSO with glycerol, and then HRSO was reacted with isophorone diisocyanate (IPDI) and hydroxyethyl acrylate (HEA) to produce the RSO-based PUA (RSO-PUA) oligomer. FT-IR and 1H NMR spectra collectively revealed that the obtained RSO-PUA was successfully synthesized, and the calculated C=C functionality of oligomer was 2.27 per fatty acid. Subsequently, a series of UV-curable resins were prepared and their ultimate properties, as well as UV-curing kinetics, were investigated. Notably, the UV-cured materials with 40% trimethylolpropane triacrylate (TMPTA) displayed a tensile strength of 11.7 MPa, an adhesion of 2 grade, a pencil hardness of 3H, a flexibility of 2 mm, and a glass transition temperature up to 109.4 °C. Finally, the optimal resin was used for digital light processing (DLP) 3D printing. The critical exposure energy of RSO-PUA (15.20 mJ/cm2) was lower than a commercial resin. In general, this work offered a simple method to prepare woody plant oil-based high-performance PUA resins that could be applied in the 3D printing industry.

The effect of triglycerides to high-density lipoprotein cholesterol ratio on the reduction of renal function: findings from China health and retirement longitudinal study (CHARLS).

BACKGROUND: Previous studies show that abnormal lipoprotein metabolism can increase the prevalence of chronic kidney disease (CKD). This study prospectively investigated the association of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio and renal dysfunction in the Chinese population. METHODS: This longitudinal cohort research examined 7,316 participants (age range: 22-93) from the China Health and Retirement Longitudinal Study (CHARLS), including 6,560 individuals with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 (normal renal function, NRF) group and 756 with eGFR < 60 mL/min/1.73 m2 (impaired renal function, IRF) group. In NRF group, reduction in renal function was defined as eGFR < 60 mL/min/1.73 m2 at exit visit and in IRF group, it was defined as decline in eGFR category, average eGFR decline > 5 mL/min/1.73 m2 per year or > 30 % decrease in eGFR from baseline. RESULTS: The study results showed that TG/HDL-C ratio was positively associated with the risk of renal function decline in the NRF group (OR 1.30, 95 %CI 1.03-1.65, P = 0.03) and the IRF group (OR 1.90, 95 %CI 1.21-3.23, P = 0.02) when adjusting for age, gender, obesity, diabetes, hypertension, waist circumference, drinking, smoking, history of heart disease and stroke, low-density lipoprotein cholesterol and eGFR category. Analysis of the IRF group indicated that relative to the group of TG/HDL-C < 1.60, the group of TG/HDL-C ≥ 2.97 had an increased risk for the decline of eGFR category (OR 1.89, 95 %CI 1.12-3.21, P = 0.02) and > 30 % decline in eGFR (OR 2.56, 95 %CI 1.05-6.38, P = 0.04). CONCLUSIONS: The high TG/HDL-C ratio was an independent risk factor for declining renal function in the Chinese population.

Short sleep duration increases the risk of hyperuricemia among Chinese adults: findings from the China Health and Nutrition Survey.

STUDY OBJECTIVES: Hyperuricemia is a growing public health problem with its increasing prevalence. Few studies have investigated the association between sleep duration and hyperuricemia. The objective of this study is to explore whether short sleep duration is an independent risk factor of hyperuricemia in Chinese adults. METHODS: The data we analyzed was extracted from the 2009 wave of the China Health and Nutrition Survey. The population we analyzed included 8289 participants aged 18 years or older with sleep of 5-10 h per 24 h. We categorized the population into three groups by sleep duration: 5-6 h (short sleeper),7-8 h (regular sleeper), and 9-10 h (long sleeper). Hyperuricemia was defined as serum uric acid ≥7 mg/dL in men and ≥6 mg/dL in women. RESULTS: Among the three groups, 9.8% were short sleepers, 68.4% were regular sleepers and 21.8% were long sleepers. The prevalences of hyperuricemia were 19.5%,15.2% and 15.5% respectively. The risks of hyperuricemia in regular and long sleep groups were lower than short sleep group, and the association remained after adjusting for indexes including age, gender, chronic kidney disease, hypertension, diabetes mellitus, high low-density lipoprotein cholesterol (LDL-c), and obesity. In subgroup analysis, we found the association was still observed in participants without hypertension, diabetes mellitus or obesity. CONCLUSIONS: Our findings suggest that short sleep duration is associated with higher risk of hyperuricemia independently of cardiometabolic risk factors, especially in individuals without traditional hyperuricemia risk factors.

GC-MS/MS method for determination and pharmacokinetics of sclareol in rat plasma after intravenous administration.

Sclareol, mainly isolated from Salvia officinalis, has a variety of pharmacological effects. In this work, a sensitive and rapid gas chromatography-tandem mass spectrometry (GC-MS/MS) method was first developed and validated for the determination and pharmacokinetics of sclareol in rat plasma. The chromatographic seperation of biosamples was performed with an HP-5MS column. Ethyl acetate was selected as the solvent to extract analytes from rat plasma. The multiple reaction monitoring transitions for sclareol and dehydrocostuslactone (Internal Standard, IS) were m/z 177 â†’ 121 and m/z 230 â†’ 173, respectively. The intra- and inter- precision, accuracy, matrix effect, recovery and stability meet the method requirements for biological sample analysis. The lowest limit of quantification (LLOQ) of the developed method for sclareol determination was 20 ng/mL. After intravenous administration (5.0 mg/kg) of sclareol to the rats, its drug clearance (CLz) and elimination half-life (t1/2z) was 2.7 ± 1.3 L/h/kg and 6.0 ± 4.6 h, respectively. The apparent volume of distribution (Vz) was 21.4 ± 12.9 L/kg, which indicated that sclareol was mainly distributed in extracellular fluid. Our results provided useful information for the further pharmacological investigation and preclinical studies of sclareol.