Intergenerational association of DNA methylation between parents and offspring.

Early patterning of DNA methylation (DNAm) may play an important role in later disease development. To better understand intergenerational epigenetic inheritance, we investigated the correlation between DNAm in blood in mother-newborn and in father-newborn pairs in the Isle of Wight (IoW) birth cohort. For parent-newborn pairs (n = 48), offspring DNAm was measured in cord blood and the parent's DNAm in whole blood. Mothers' DNAm was analyzed at birth (Guthrie card), age 18, early and late pregnancy respectively, and fathers' DNAm was measured during the mother's pregnancy. Linear regressions were applied to assess the intergenerational correlation of parental DNAm with that of offspring. Among various pairs of mother-newborn and father-newborn DNAm, the pairs where the mothers' DNAm was measured at age 18 years exhibited the highest number of CpGs with significant intergenerational correlation in DNAm, with 1829 CpGs (0.54%) of the 338,526 CpGs studied (FDR < 0.05). Amongst these 1829 CpGs, 986 (54%) are known quantitative trait loci (QTL) for CpG methylation (methQTL). When the mother's DNAm was assessed at early pregnancy, the number of CpGs showing intergenerational correlation was the smallest (384 CpGs, 0.11%). The second smallest number of such CpGs (559 CpGs, 0.17%) was found when investigating DNAm in offspring cord blood and father pairs. The low proportions of intergenerationally correlated CpGs suggest that epigenetic inheritance is limited.

Unlocking the potential: strategic synthesis of a previously predicted pyrazolate-based stable MOF with unique clusters and high catalytic activity.

The metal-organic framework (MOF) constructed from [Co4Pz8] clusters (Pz = pyrazolate) and 1,3,5-tris(pyrazolate-4-yl) benzene (BTP3-) ligands was structurally predicted many years ago, and expected to be a promising candidate for various applications owing to its unique clusters and highly open 3D framework structure. However, this MOF has not been experimentally prepared yet, despite extensive efforts were made. In this work, we present the successful construction of this MOF, hereinafter referred to as BUT-124(Co), by adopting a two-step synthesis strategy, involving the initial construction of a template framework (BUT-124(Cd)) followed by a post-synthetic metal metathesis process. The effects of various cobalt sources and solvents were systematically investigated, and an innovative stepwise metathesis strategy was employed to optimize the exchange rates and the porosity of the material. BUT-124(Co) demonstrates high catalytic activity in the oxygen evolution reaction (OER), achieving a competitive performance with an overpotential of 393 mV at a current density of 10 mA cm-2, and also affords remarkable long-term stability during potentiostatic electrolysis in 1 M KOH solution, surpassing the durability of many benchmark catalysts. This work not only introduces a novel MOF material with promising properties but also exemplifies a strategic synthesis approach for pyrazolate-based MOFs, paving the way for advancements in diverse application fields.

Silvaticusins A-D: ent-kaurane diterpenoids and a cyclobutane-containing ent-kaurane dimer from Isodon silvaticus.

Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 µM.

Lactococcus strains with psychobiotic properties improve cognitive and mood alterations in aged mice.

Aging often accompanies cognitive and mood disturbances. Emerging evidence indicates that specific probiotics mitigate cognitive and mood dysfunctions. Strains within Lactococcus, a subgroup of probiotics, including Lactococcus lactis and Lactococcus cremoris are shown beneficial effects on brain functions via the gut microbiota-brain axis (GBA). Our previous study identified two Lactococcus strains (L. lactis WHH2078 and L. cremoris WHH2080) with the ability to promote the secretion of gut 5-hydroxytryptophan (5-HTP), the precursor of the GBA mediator 5-hydroxytryptamine (5-HT). In this study, the modulatory effects of WHH2078 and WHH2080 on cognitive and mood alternations were investigated in aged mice. Oral administration of WHH2078 and WHH2080 (1 × 109 CFU/mL/day) in aged mice (12-month-old) for 12 weeks significantly improved cognitive and depressive-and anxiety-like behaviors. The neuronal loss, the 5-HT metabolism dysfunction, and the neuroinflammation in the hippocampus of aged mice were restored by WHH2078 and WHH2080. the disturbances in the serum tryptophan metabolism in aged mice were unveiled by metabolomics, notably with decreased levels of 5-HT and 5-HTP, and increased levels of kynurenine, 3-hydroxykynurenine, and indolelactic acid, which were reversed by WHH2078 and WHH2080. Regarding the gut microbial community, WHH2078 and WHH2080 restored the increased abundance of Firmicutes, Desulfobacterota, and Deferribacterota and the decreased abundance of Bacteroidota and Actinobacteriota in aged mice. The beneficial effects of the two strains were linked to the modulation of 5-HT metabolism and gut microbiota. Our findings point to the potential role of Lactococcus strains with 5-HTP-promoting abilities as therapeutic approaches for age-related cognitive and mood disorders.

FAM134B deletion exacerbates apoptosis and epithelial-to-mesenchymal transition in rat lungs exposed to hyperoxia.

Oxygen therapy is widely used in clinical practice; however, prolonged hyperoxia exposure may result in hyperoxic acute lung injury (HALI). In this study, we investigated the role of FAM134B in hyperoxia-induced apoptosis, cell proliferation, and epithelial-to-mesenchymal transition (EMT) using RLE-6TN cells and rat lungs. We also studied the effect of CeO2-NPs on RLE-6TN cells and lungs following hyperoxia exposure. FAM134B was inhibited in RLE-6TN cells and rat lungs following hyperoxia exposure. Overexpressing FAM134B promoted cell proliferation, and reduced EMT and apoptosis following hyperoxia exposure. FAM134B activation increased ER-phagy, decreased apoptosis, improved lung structure damage, and decreased collagen fiber deposition to limit lung injury. These effects could be reversed by PI3K/AKT pathway inhibitor LY294002. Additionally, CeO2-NPs protected RLE-6TN cells and lung damage following hyperoxia exposure by ameliorating impaired ER-phagy. Therefore, FAM134B restoration is a potential therapeutic target for the HALI. Moreover, CeO2-NPs can be used for the treatment of HALI.

Prophylactic effects of supplementation of a combination of Lactobacillus lactis WHH2078 and saffron on depressive-like behaviors in mice exposed to chronic stress.

Depression is one of the most common psychiatric conditions worldwide, with an annual escalation in prevalence. The serotonin (5-Hydroxytryptamine [5-HT]) metabolism through the gut-brain axis has been revealed to be related to the development of depression. Our previous study demonstrated that Lactococcus lactis WHH2078 alleviated depression in mice by shaping the gut microbiome composition and 5-HT metabolism. However, little research has explored the synergistic effects of probiotics and natural mental health-improving products. In this study, three natural products (saffron, l-theanine, and phosphatidylserine), either individually or in combination, were orally administrated for 4 weeks in chronic restraint stress (CRS)-induced mice, and their depressive behaviors, hippocampal 5-HT, and serum corticosterone were assessed. Saffron demonstrated improvement of the depressive-like behaviors via multiple behavioral tests and reversed the declined concentration of 5-HT and increased concentration of corticosterone. Following an initial screening, saffron was chosen to be combined with WHH2078, referred to as WHHMOOD™. Furthermore, the effects of WHHMOOD were evaluated in mice with depressive-like behaviors. WHHMOOD reduced immobility time in the forced swimming test and tail suspension test, increased the time spent in the central area in open field test, and reduced the serum corticosterone level. Besides, WHHMOOD improved the CRS-induced gut microbial dysbiosis by reversing gut microbial diversity and the abundances of Ligilactobacillus, Candidatus Arthromitus, and Erysipelatoclostridium. Compared to WHH2078, WHHMOOD treatment significantly increased the travel distance and hippocampal 5-HT level in mice. In conclusion, WHHMOOD exhibited prophylactic effects on depressive-like in CRS mice, which may act as a promising agent for improving the symptoms of depression.

Traditional Chinese-version reliability test of the Pieper-Zulkowski pressure ulcer knowledge: Psychometric and assessment.

This study was to translate the Pieper-Zulkowski pressure ulcer knowledge test (PZ-PUKT) into Traditional Chinese and evaluate its psychometric properties as well as identify the predictors of knowledge on pressure injury. The PZ-PUKT was translated into Traditional Chinese (TC-PZ-PUKT), and its content validity was evaluated. A total of 296 nurses participated in this study and completed the 72-item TC-PZ-PUKT online. The reliability of the TC-PZ-PUKT was analysed by evaluating its internal consistency and test-retest reliability. Hierarchical regression was used to determine factors associated with TC-PZ-PUKT scores. Content validity was achieved with a score of 0.986. Internal consistency was observed to be reliable, with a Cronbach's alpha of 0.858. The mean knowledge score on the TC-PZ-PUKT was 72.5%, with a 1-week test-retest reliability of r = 0.849. Education level, certification as a wound specialist and self-learning through reading articles, books or guidelines on pressure injury were significantly associated with TC-PZ-PUKT scores. The TC-PZ-PUKT is a valid and reliable tool. Education level, certification as a wound specialist and self-learning regarding pressure injury are related to knowledge of pressure injury.

Segmental mandibulectomy and microvascular reconstruction with fibula free flap: Comparison between intraoral and extraoral approaches.

BACKGROUND: Segmental mandibulectomy and reconstruction of resulting defect can be performed via intraoral approach (IOA) or extraoral approach (EOA). Both approaches have advantages, disadvantages, indications, and contraindications to consider during their selection. OBJECTIVE: To compare IOA vs EOA of segmental mandibulectomy and microvascular reconstruction with fibula free flap (FFF). METHODS: We conducted a retrospective cohort study in which 51 patients who underwent segmental mandibulectomy and microvascular reconstruction with FFF from 2020 to 2024 were included, especially 17 patients by IOA and 34 patients by EOA, representing both groups of this study. Clinical characteristics, surgery parameters, and patients' prognosis were evaluated. Patients' satisfaction and Derriford Appearance Scale (DAS59) were assessed during follow-up. RESULTS: Ameloblastoma was the most frequent diagnosis (52.9% managed by IOA vs 70.6% by EOA); FFF was frequently positioned as double barrel (94.1% managed by IOA vs 88.2% by EOA). Compared with EOA group, IOA group had less intraoperative blood loss (mean difference [MD] = -112.2, 95% confidence interval [CI]: -178.9 to -45.5, p = 0.001), higher satisfaction score (MD = 1.3, 95% CI: 0.9 to 1.7, p ˂ 0.001), and lower DAS59 score (MD = -0.5, 95% CI: -0.7 to -0.2, p ˂ 0.001). CONCLUSION: Both IOA and EOA were found safe and feasible, presenting similar perioperative features and postoperative outcomes. Patients managed with IOA were more satisfied with aesthetic outcomes than patients managed with EOA. In the absence of simultaneous immediate implant during mandibular FFF reconstruction, after stability of FFF on the defect site, patients should always be referred to an implantologist and/or prosthodontist for teeth restoration to improve functional and aesthetic outcomes.

Correlation between inflammatory cytokines and the likelihood of developing multiple types of digestive system cancers: A Mendelian randomization study.

OBJECTIVE: Inflammatory cytokines have been linked to digestive system cancers, yet their exact causal connection remains uncertain. Consequently, we conducted a Mendelian randomization (MR) analysis to gauge how inflammatory cytokines are linked to the risk of five prevalent digestive system cancers (DSCs). METHODS: We collected genetic variation data for 41 inflammatory cytokines from genome-wide association studies (GWAS), and the results data for five common diseases from the Finnish database. Our primary analytical approach involved employing the inverse-variance weighted, residual sum (IVW) method, complemented by the MR-Egger method, the weighted median method, simple mode analysis, and weighted mode analysis as supplementary analytical techniques. Furthermore, we conducted multiple sensitivity analyses. RESULTS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-18 showed a negative association with the risk of hepatocellular carcinoma. Conversely, TRAIL was inversely linked to the risk of gastric cancer, while IL-16 exhibited a positive correlation with gastric cancer risk. Stem cell factor (SCF) acted as a protective factor against pancreatic cancer. For colorectal cancer, IL-7, IL-9, IL-13, and vascular endothelial growth factor (VEGF) were identified as risk factors. Notably, our results did not indicate a significant correlation between inflammatory cytokines and the risk of esophageal cancer. CONCLUSION: Our research unveils potential connections between 41 inflammatory cytokines and the risk of five common DSCs through a MR analysis. These associations offer valuable insights that could aid in the development of diagnostic biomarkers and the identification of novel therapeutic targets for DSCs.

Structurally diverse ent-clerodanoids from the aerial parts of Isodon scoparius.

Scoparodane C (1), a diterpenoid with a rare 3,4-seco-3-nor-2,11-epoxy-ent-clerodane scaffold, was obtained from the aerial parts of Isodon scoparius, along with isocopariusines A-E (2-6), five ent-clerodanoids featuring a 5/6-fused ring system, and isocopariusines F-H (7-9), three common ent-clerodanoids. The structures of these previously undescribed compounds were established by a combination of spectroscopic analysis, X-ray diffraction, chemical derivatization, and quantum chemical calculation. Remarkably, isocopariusine B (3) showed strong resistance reversal activity against fluconazole-resistant Candida albicans.

Enhancing reductive dechlorination of trichloroethylene in bioelectrochemical systems with conductive materials.

The incorporation of conductive materials to enhance electron transfer in bioelectrochemical systems (BES) is considered a promising approach. However, the specific effects and mechanisms of these materials on trichloroethylene (TCE) reductive dechlorination in BES remains are not fully understood. This study investigated the use of magnetite nanoparticles (MNP) and biochars (BC) as coatings on biocathodes for TCE reduction. Results demonstrated that the average dechlorination rates of MNP-Biocathode (122.89 µM Cl·d-1) and BC-Biocathode (102.88 µM Cl·d-1) were greatly higher than that of Biocathode (78.17 µM Cl·d-1). Based on MATLAB calculation, the dechlorination rate exhibited a more significantly increase in TCE-to-DCE step than the other dechlorination steps. Microbial community analyses revealed an increase in the relative abundance of electroactive and dechlorinating populations (e.g., Pseudomonas, Geobacter, and Desulfovibrio) in MNP-Biocathode and BC-Biocathode. Functional gene analysis via RT-qPCR showed the expression of dehalogenase (RDase) and direct electron transfer (DET) related genes was upregulated with the addition of MNP and BC. These findings suggest that conductive materials might accelerate reductive dechlorination by enhancing DET. The difference of physicochemical characteristics (e.g. particle size and specific surface area), electron transfer enhancement mechanism between MNP and BC as well as the reduction of Fe(III) by hydrogen may explain the superior dechlorination rate observed with MNP-Biocathode.

Anomalous normal-state gap in an electron-doped cuprate.

In the underdoped n-type cuprate Nd2-xCexCuO4, long-range antiferromagnetic order reconstructs the Fermi surface, resulting in a putative antiferromagnetic metal with small Fermi pockets. Using angle-resolved photoemission spectroscopy, we observe an anomalous energy gap, an order of magnitude smaller than the antiferromagnetic gap, in a wide portion of the underdoped regime and smoothly connecting to the superconducting gap at optimal doping. After considering all the known ordering tendencies in tandem with the phase diagram, we hypothesize that the normal-state gap in the underdoped n-type cuprates originates from Cooper pairing. The high temperature scale of the normal-state gap raises the prospect of engineering higher transition temperatures in the n-type cuprates comparable to those of the p-type cuprates.

Cancer-Associated-Fibroblast-Mediated Paracrine and Autocrine SDF-1/CXCR4 Signaling Promotes Stemness and Aggressiveness of Colorectal Cancers.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.

The impact of the doctor-nurse-patient workshop transitional care model on the post-operative quality of life of patients with laryngeal cancer.

OBJECTIVE: The aim of this study is to assess the efficacy of the doctor-nurse-patient workshop transitional care model on post-operative care for patients with laryngeal cancer and its influence on quality of life. METHODS: A total of 68 patients with laryngeal cancer who underwent surgical treatment at the hospital between 2021 and 2022 were included in the study. The patients were divided into two groups, a control group and a research group, each consisting of 34 patients, based on the chronological sequence of their surgeries. Patients in the control group received standard nursing care, while those in the research group received the doctor-nurse-patient workshop transitional care model in addition to standard nursing care. After 2 months of care, levels of albumin (ALB), total protein (TP), hemoglobin (Hb), and quality of life scores (measured using the Quality of Life Instrument for Head and Neck Cancer, QLICP-HN) were compared between the two groups. Additionally, the incidence of adverse events during the recovery period was assessed and compared between the two groups. RESULTS: Following 2 months of care, patients in the research group exhibited elevated ALB, TP, and Hb levels compared to those in the control group. Additionally, the average QLICP-HN scores were higher in the research group, while the incidence of adverse events was lower compared to the control group. CONCLUSION: Implementing the doctor-nurse-patient workshop transitional care model in home care for patients with laryngeal cancer can enhance their nutritional status post-surgery and improve their quality of life during home rehabilitation. This, in turn, leads to a reduction in the incidence of adverse events and complications during the recovery period.

Effects of Virtual Reality on Pain and Anxiety During Children's Circumcision: A Systematic Review and Meta-Analysis.

BACKGROUND: Circumcision-a common pediatric procedure-can cause significant pain and anxiety. Virtual reality has been proposed as a nonpharmacological intervention to alleviate these negative experiences. OBJECTIVE: This systematic review and meta-analysis was conducted to evaluate the effects of virtual reality interventions on pain and anxiety in children undergoing circumcision. METHODS: This study comprehensively searched PubMed, Embase, and Cochrane Library for articles published from database inception to October 2, 2023. Randomized controlled trials that investigated the effects of virtual reality interventions on pain and anxiety during circumcision in children were included. The Cochrane risk-of-bias tool was used to appraise the included studies. The primary outcomes were pain and anxiety scores. RESULTS: Three randomized controlled trials and four data sets involving a total of 224 children were included in our meta-analysis. Virtual reality interventions significantly reduced children's pain and anxiety scores. CONCLUSIONS: Virtual reality interventions are promising nonpharmacological strategies for alleviating children's pain and anxiety during circumcision. Pediatric healthcare professionals use virtual reality interventions to create a child-friendly and healthy healthcare environment.

Identification and transcriptome analysis of a photosynthesis deficient mutant of Populus davidiana Dode.

Photosynthesis is the main source of energy for plants to sustain growth and development. Abnormalities in photosynthesis may cause defects in plant development. The elaborate regulatory mechanism underlying photosynthesis remains unclear. In this study, we identified a natural mutant from the Greater Khingan Mountains and named it as "1-T". This mutant had variegated leaf with irregular distribution of yellow and green. Chlorophyll contents and photosynthetic capacity of 1-T were significantly reduced compared to other poplar genotypes. Furthermore, a transcriptome analysis revealed 3269 differentially expressed genes (DEGs) in 1-T. The products of the DEGs were enriched in photosystem I and photosystem II. Three motifs were significantly enriched in the promoters of these DEGs. Yeast one-hybrid, Electrophoretic mobility shift assays and tobacco transient transformation experiments indicated that PdGLKs may bind to the three motifs. Further analysis indicated that these photosystem related genes were also significantly down-regulated in PdGLK-RNAi poplars. Therefore, we preliminarily concluded that the down-regulation of PdGLKs in 1-T may affect the expression of photosystem-related genes, resulting in abnormal photosystem development and thus affecting the growth and development. Our results provide new insights into the molecular mechanism of photosynthesis regulating plant growth.

Beneficial effects of Dendrobium officinale National Herbal Drink on metabolic immune crosstalk via regulate SCFAs-Th17/Treg.

BACKGROUND: The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied. OBJECTIVES: The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake. METHODS: In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 ml/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16S rRNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk. RESULTS: Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured_bacterium_g__norank_f__muribaculacea and uncultured_bacterium_g__Turicibacter. Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4+T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder. CONCLUSIONS: Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4+T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis.

Gender Differences in Patients with Atrial Fibrillation Receiving Oral Anticoagulants.

Background: Gender is a well-recognized risk factor in atrial fibrillation (AF)-related ischemic stroke. The association of gender with the use of oral anticoagulants (OACs) and prognosis remains unknown. Methods: The National Health Insurance Research Database in Taiwan identified 203,775 patients with AF aged ≥ 20 years from 2012 to 2018, with 55.4% of males. Our main study cohort included 67,426 patients using OACs. The study endpoints include death, ischemic stroke, intracranial hemorrhage, major bleeding, and composite adverse events. Results: Significant differences were found in baseline characteristics between sexes. Female patients with AF were older and had higher CHA 2 DS 2 -VASc and HAS-BLED scores. Non-vitamin K antagonist oral anticoagulant (NOAC) use was more prominent in females while the use of warfarin was similar in both sexes. The distribution of baseline characteristics between the warfarin and NOAC groups in both sexes was much alike. Among the whole study cohort, NOAC was associated with a decreased risk of clinical endpoints compared to warfarin, which remained the same in subgroup analyses of both sexes. Additionally, a greater risk reduction of ischemic stroke with NOAC was observed in female patients compared to male patients (adjusted hazard ratio: 0.517 in males, 0.425 in females, interaction p = 0.040). Conclusions: This nationwide cohort demonstrated the differences between male and female patients with AF, including baseline characteristics, risk profiles, and medication use. Despite great differences in baseline demographic data, NOAC was associated with better clinical outcomes compared to warfarin in both sexes, and females benefited more than males in preventing ischemic stroke using NOACs.

Multifunctional and bioinspired titanium surface with multilayer nanofilms for novel dental implant applications.

Introduction: Smart multifunctional surfaces targeting intricate biological events or versatile therapeutic strategies are imminent to achieve long-term transmucosal implant success. Methods: This study used dopamine (DA), graphene oxide (GO), and type IV collagen (COL-IV) to construct multilayer nanofilms (DGCn) based on their universal adhesive and biomimetic properties to design a versatile and bioactive titanium implant. The characterization of DGCn on different titanium surfaces was performed, and its loading capacity, release profile, in situ gene delivery, and in vitro biological properties were preliminarily evaluated. Results: Our results demonstrate that hydrogenated TiO2 nanotubes (H) provide a better platform for the DGCn coating than machined Ti and air-TiO2 nanotubes. The H-DGC10 displayed the most stable surface with excellent loading capacity, sustained-release profile, and in situ gene transfection efficiency; this could be due to the high specific surface area of H and GO, as well as the functional groups in H, DA, and GO. Moreover, the H-DGC10 exhibited good biocompatibility for human oral epithelial cells and promoted the expression of integrin ß4 and laminin 332, both being hemidesmosome-related proteins. Discussion: Our findings suggest that H-DGCn can be designed as a smart multifunctional interface for titanium implants to achieve long-term transmucosal implant success and aid in versatile therapeutic strategies.

[Effect of polymethoxylated flavonoids on glucose and lipid metabolism in rat model of obesity induced by a high-fat diet].

This study established a rat model of obesity by using a high-fat diet(HFD) to explore the effect of polymethoxylated flavonoids on glucose and lipid metabolism in the model rats and decipher the role and mechanism of polymethoxylated flavonoids in mitigating obesity. Thirty normal SD rats were selected and randomized into normal, model, ezetimibe(0.1 mg·kg~(-1)), and polymethoxylated flavonoids(62.5 mg·kg~(-1) and 125 mg·kg~(-1)) groups based on the body weight. Except the normal group receiving a conventional diet, the other groups received a HFD. Rats were administrated with corresponding doses of drugs by gavage. During the administration period, the body weight of each group of rats was regularly weighed, and the serum lipid and glucose levels were measured by a fully automated biochemical analyzer. Islet homeostasis and serum levels of obesity factors were measured by ELISA. The 16S rRNA high-throughput sequencing was employed to study the gut microbiota. Hematoxylin-eosin staining was employed to observe the histomorphology of white fat, brown fat, and pancreas. After the wet weights of white fat and brown fat were measured, the organ index was calculated. Immunohistochemistry and Western blot were employed to determine the protein levels. The results showed that polymethoxylated flavonoids reduced the body weight and Lee's index and improved blood lipid levels of the model rats. Polymethoxylated flavonoids reduced blood glucose and insulin secretion, increased insulin responsiveness, and alleviated insulin resistance. In addition, polymethoxylated flavonoids regulated the serum levels of obesity factors and reduced the weights and indexes of white fat and brown fat, the diameter of white adipocytes, and the number of fat vacuoles in brown fat and pancreatic islet cells. The intervention with polymethoxylated flavonoids increased the diversity of gut microbiota in the model rats, increasing the beneficial bacteria associated with glucose and lipid metabolism and reduced the harmful bacteria at the genus level. In addition, polymethoxylated flavonoids up-regulated the protein levels of glucose transporter 4(GLUT4), phosphorylated AMP-activated protein kinase(p-AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and uncoupling protein 1(UCP1). In summary, polymethoxylated flavonoids may increase the body utilization of glucose and lipids by regulating the homeostasis of insulin, the serum levels of obesity factors, the diversity of gut microbiota, and the expression of mitochondrial metabolism-related proteins in brown adipocytes, thereby mitigating obesity in rats.