Vaccination induces broadly neutralizing antibody precursors to HIV gp41.

A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

New Approach for Preparation of Porous Polymers with Reversible Pore Structures for a Highly Safe Smart Supercapacitor.

Porous polymers have many industrial applications, but their pore structures (open or closed) are usually fixed during polymerization. In this study, polymers with reversible and controllable pore structures, namely, thermosensitive porous hydrogels with regulated volume phase transition temperature, were prepared using a Pickering high-internal-phase emulsion as the template. Upon heating, the hydrogels transformed not only in their wettability (between hydrophilicity and hydrophobicity with water contact angles of 21.8 and 100.9°) but also their pore structure (between open through-holes and closed holes with pore throat sizes of 15.58 and 0 µm, respectively) in a short time (<10 s). When the hydrogel was used as a separator in smart supercapacitors (SCs), this behavior effectively limited the path of electrolyte migration, reducing the chance of conflagration accidents. Moreover, by utilizing the highly reversible pore structures and wettability of the porous hydrogel, reversible charging and discharging were restored after the system cooled down. This work not only provides great guidance for preparing porous polymers with reversible pore structures but also paves the way for designing smart SCs with enhanced safety.

Enhancing Polyvinyl Alcohol Nanocomposites with Carboxy-Functionalized Graphene: An In-Depth Analysis of Mechanical, Barrier, Electrical, Antibacterial, and Chemical Properties.

To enhance the various properties of polyvinyl alcohol (PVA), varying concentrations of carboxy-functionalized graphene (CFG) were employed in the preparation of CFG/PVA nanocomposite films. FTIR and XRD analyses revealed that CFG, in contrast to graphene, not only possesses carboxylic acid group but also exhibits higher crystallinity. Mechanical testing indicated a notable superiority of CFG addition over graphene, with optimal mechanical properties such as tensile and yield strengths being achieved at a 3% CFG concentration. Relative to pure PVA, the tensile strength and yield strength of the composite increased by 2.07 and 2.01 times, respectively. XRD analysis showed distinct changes in the crystalline structure of PVA with the addition of CFG, highlighting the influence of CFG on the composite structure. FTIR and XPS analyses confirmed the formation of ester bonds between CFG and PVA, enhancing the overall performance of the material. TGA results also demonstrated that the presence of CFG enhanced the thermal stability of CFG/PVA nanocomposite films. However, analyses using scanning electron microscopy and transmission electron microscopy revealed that a 3% concentration of CFG was uniformly dispersed, whereas a 6% concentration of CFG caused aggregation of the nanofiller, leading to a decrease in performance. The incorporation of CFG significantly enhanced the water vapor and oxygen barrier properties of PVA, with the best performance observed at a 3% CFG concentration. Beyond this concentration, barrier properties were diminished owing to CFG aggregation. The study further demonstrated an increase in electrical conductivity and hydrophobicity of the nanocomposites with the addition of CFG. Antibacterial tests against E. coli showed that CFG/PVA nanocomposites exhibited excellent antibacterial properties, especially at higher CFG concentrations. These findings indicate that CFG/PVA nanocomposites, with an optimized CFG concentration, have significant potential for applications requiring enhanced mechanical strength, barrier properties, and antibacterial capabilities.

A Facile Surface Modification Scheme for Medical-Grade Titanium and Polypropylene Using a Novel Mussel-Inspired Biomimetic Polymer with Cationic Quaternary Ammonium Functionalities for Antibacterial Application.

Medical device-associated infection remains a critical problem in the healthcare setting. Different clinical- or device-related methods have been attempted to reduce the infection rate. Among these approaches, creating a surface with bactericidal cationic functionality has been proposed. To do so, a sophisticated multi-step chemical procedure would be needed. Instead, a simple immersion approach was utilized in this investigation to render the titanium and polypropylene surface with the quaternary ammonium functionality by using a mussel-inspired novel lab-synthesized biomimetic catechol-terminated polymer, PQA-C8. The chemical oxidants, CuSO4/H2O2, as well as dopamine, were added into the novel PQA-C8 polymer immersion solution for one-step surface modification. Additionally, a two-step immersion scheme, in which the polypropylene substrate was first immersed in the dopamine solution and then in the PQA-C8 solution, was also attempted. Surface analysis results indicated the surface characteristics of the modified substrates were affected by the immersion solution formulation as well as the procedure utilized. The antibacterial assay has shown the titanium substrates modified by the one-step dopamine + PQA-C8 mixtures with the oxidants added and the polypropylene modified by the two-step scheme exhibited bacterial reduction percentages greater than 90% against both Gram-positive S. aureus and Gram-negative E. coli and these antibacterial substrates were non-cytotoxic.

HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs.

BACKGROUND: Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. METHODS: From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg-/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. RESULTS: During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 person-years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9-186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12-60.32, p = .001), abatacept (aHR: 9.30, 1.83-47.19, p = .007), adalimumab (aHR: 3.86, 1.05-14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70-8.92, p < .001) were independent risk factors for HBV reactivation. CONCLUSION: HBsAg-/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy.

The influence of sex difference on behavior and adult hippocampal neurogenesis in C57BL/6 mice.

Animal models have been used extensively in in vivo studies, especially within the biomedical field. Traditionally, single-sex studies, mostly males, are used to avoid any potential confounding variation caused by sex difference and the female estrous cycle. Historically, female animal subjects are believed to exhibit higher variability, and this could increase the statistical power needed to test a hypothesis. This study sets out to evaluate whether a sex difference does exist in mouse behavior, and whether female mice featured higher variability. We assessed the sensorimotor skills, anxiety-like behavior, depression-like behavior, and cognitive abilities of mice through a series of commonly used behavioral tests. Except for the stronger grip force and lower tactile sensory sensitivity detected in male mice, there was no significant difference between males and females in other tests. Furthermore, immunolabeling of neurogenesis markers suggested no significant difference between sexes in adult hippocampal neurogenesis. Within group variances were equivalent; females did not exhibit higher variability than males. However, the overall negative results could be due to the limitation of small sample size. In conclusion, our study provides evidence that sex difference in mice does not significantly influence these commonly used behavioral tests nor adult neurogenesis under basal conditions. We suggest that female mice could also be considered for test inclusion in future experiment design.

Polymer Packaging through the Blending of Biowaste Oyster Shell and Low-Density Polyethylene: A Sustainable Approach for Enhanced Food Preservation.

This research delves into the impact of incorporating thermally treated oyster shell powder (TOS), a biowaste filler, into low-density polyethylene (LDPE) to develop a LDPE/TOS blend, aiming at enhancing food packaging materials. The LDPE/TOS blend portrays advantageous characteristics such as augmented mechanical strength, thermostability, crystallinity, water absorption, and improved hydrophobicity with TOS content up to 50%. Microstructure analysis reveals a transition from a sparse to a more interconnected structure, contributing to the amplified tensile strength. The blend demonstrates increased barrier properties against water vapor transmission, which is attributed to elongated diffusion paths induced by the TOS particles. Application of the blend material in vegetable preservation trials manifested a substantial reduction in water loss compared to pure LDPE or no packaging. This biowaste-based blend film extends the shelf-life of chicken significantly when compared to that of pure LDPE. Importantly, the LDPE/TOS blend exhibits excellent antibacterial properties against both Escherichia coli and Staphylococcus aureus.

Stimulation-responsive mucoadhesive probiotics for inflammatory bowel disease treatment by scavenging reactive oxygen species and regulating gut microbiota.

Inflammatory bowel disease (IBD) is characterized by the high level of reactive oxygen species (ROS) and highly dysfunctional intestinal flora. Here, a stimulation-responsive mucoadhesive probiotic Lac@HDP was rationally constructed for achieving specific adhesion of colitis site and depleting high level of ROS in inflammatory site. Briefly, Lac is Lactobacillus acidophilus, HDP is obtained by hyaluronic acid grafted with dopamine protected by phenylboric acid. Specifically, by consuming a large amount of ROS, phenyl borate group of Lac@HDP is oxidized and fractured, thus exposing the catechol hydroxyl group and obtaining strong mucosal adhesion ability, thereby significantly prolong the retention time of Lac in the inflammatory site. In the murine model of acute and chronic colitis, the stimulation-responsive mucoadhesive probiotics were significantly more effective in alleviating colitis symptoms than antioxidants and probiotics alone. In addition, the abundance and diversity of intestinal flora were increased after treatment with Lac@HDP, which was helpful to alleviate IBD. Importantly, the stimulation-responsive mucoadhesive probiotics have good biological safety in vivo, which provides the prospect of clinical application in the future.

Improving Mechanical and Barrier Properties of Antibacterial Poly(Phenylene Sulfide) Nanocomposites Reinforced with Nano Zinc Oxide-Decorated Graphene.

Nano zinc oxide-decorated graphene (G-ZnO) was blended with polyphenylene sulfide (PPS) to improve its tensile, thermal, crystalline, and barrier properties. The properties of neat PPS and PPS/G-ZnO nanocomposites were characterized and compared using various tests, including tensile tests, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, evaluation of Escherichia coli inhibition, and barrier performance. The results demonstrated that G-ZnO played a crucial role in heterogeneous nucleation and reinforcement. When the concentration of G-ZnO was 0.3%, the tensile strength, elongation at break, thermostability, crystallinity, and water vapor permeability coefficients (WVPC) approached their maximum values, and the microscopic morphology changed from the original brittle fracture to a relatively tough fracture. In addition, when G-ZnO was added to PPS at a ratio of 0.3%, the tensile strength, elongation at break, and WVPC of PPS were increased by 129%, 150%, and 283%, respectively, compared to pure PPS. G-ZnO endowed the nanocomposites with antibacterial properties. The improvement in barrier performance can be attributed to three reasons: (1) the presence of G-ZnO extended the penetration path of molecules; (2) the coordination and hydrogen bonds between PPS polymer matrix and G-ZnO nanofiller narrowed the H2O transmission path; and (3) due to its more hydrophobic surface, water molecules were less likely to enter the interior of PPS/G-ZnO nanocomposites. This study provides valuable insights for developing high-performance PPS-based nanocomposites for various applications.

Discovery of tetrasubstituted thiophenes as Cisd2 activators: A potential novel therapeutic option in nonalcoholic fatty liver disease.

Down-regulation of Cisd2 in the liver has been implicated in the development of nonalcoholic fatty liver disease (NAFLD) and increasing the level of Cisd2 is therefore a potential therapeutic approach to this group of diseases. Herein, we describe the design, synthesis, and biological evaluation of a series of Cisd2 activators, all thiophene analogs, based on a hit obtained using two-stage screening and prepared via either the Gewald reaction or by intramolecular aldol-type condensation of an N,S-acetal. Metabolic stability studies of the resulting potent Cisd2 activators suggest that thiophenes 4q and 6 are suitable for in vivo studies. The results from studies on 4q-treated and 6-treated Cisd2hKO-het mice, which carry a heterozygous hepatocyte-specific Cisd2 knockout, confirm that (1) there is a correlation between Cisd2 levels and NAFLD and (2) these compounds have the ability to prevent, without detectable toxicity, the development and progression of NAFLD.

Design of Intelligent Protective Composite Material with Stress Rate Sensitivity, Strong Interface Adhesion, and Recyclability.

Poly(dimethyl siloxane) (PDMS) elastomers play a significant role in smart materials, actuators, and flexible electronics. However, current PDMS lacks adhesion abilities and intelligent responsive properties, which limit its further application. In this study, the polydimethylsiloxane-ureidopyrimidinone impact hardening polymer (PDMS-UI) composites are manufactured by a dual cross-linking compositing tactic. PDMS, a chemically stable cross-linked network, acts as a framework owing to its excellent mechanical strength, whereas UI, a reversible dynamic physically cross-linked network with quadruple hydrogen bonding, endows the PDMS-UI with excellent self-healing ability (efficiency > 90%) and energy absorption (75.23%). Impressively, owing to multivalent hydrogen bonds, the PDMS-UI exhibits superior adhesion performance: the adhesion strength on various substrates exceed 150 kPa and that on the Ferrum substrate reaches 570 kPa. These outstanding properties make the PDMS-UI a potential candidate for application in both well-developed fields, such as, wearable protective materials, artificial skin and soft robotics.

Characterization and Morphology of Nanocomposite Hydrogels with a 3D Network Structure Prepared Using Attapulgite-Enhanced Polyvinyl Alcohol.

In this investigation, purified attapulgite (ATT) and polyvinyl alcohol (PVA) were utilized to fabricate nanocomposite hydrogels and a xerogel, with a focus on studying the impact of minor additions of ATT on the properties of the PVA nanocomposite hydrogels and xerogel. The findings demonstrated that at a concentration of 0.75% ATT, the water content and gel fraction of the PVA nanocomposite hydrogel reached their peak. Conversely, the nanocomposite xerogel with 0.75% ATT reduced its swelling and porosity to the minimum. SEM and EDS analyses revealed that when the ATT concentration was at or below 0.5%, nano-sized ATT could be evenly distributed in the PVA nanocomposite xerogel. However, when the concentration of ATT rose to 0.75% or higher, the ATT began to aggregate, resulting in a decrease in porous structure and the disruption of certain 3D porous continuous structures. The XRD analysis further affirmed that at an ATT concentration of 0.75% or higher, a distinct ATT peak emerged in the PVA nanocomposite xerogel. It was observed that as the content of ATT increased, the concavity and convexity of the xerogel surface, as well as the surface roughness, decreased. The results also confirmed that the ATT was evenly distributed in the PVA, and a combination of hydrogen bonds and ether bonds resulted in a more stable gel structure. The tensile properties exhibited that when compared with pure PVA hydrogel, the maximum tensile strength and elongation at break were achieved at an ATT concentration of 0.5%, indicating increases of 23.0% and 11.8%, respectively. The FTIR analysis results showed that the ATT and PVA could generate an ether bond, further confirming that ATT could enhance the PVA properties. The TGA analysis showed that the thermal degradation temperature peaked when the ATT concentration was at 0.5%, providing further evidence that the compactness of the nanocomposite hydrogel and the dispersion of the nanofiller was superior, contributing to a substantial increase in the mechanical properties of the nanocomposite hydrogel. Finally, the dye adsorption results displayed a significant rise in dye removal efficiency for methylene blue with the increase in the ATT concentration. At an ATT concentration of 1%, the removal efficiency rose by 103% compared with that of the pure PVA xerogel.

Physical exercise attenuates age-related muscle atrophy and exhibits anti-ageing effects via the adiponectin receptor 1 signalling.

BACKGROUND: Although the adiponectin signalling exerts exercise-mimicking effects, whether this pathway contributes to the anti-ageing benefits of physical exercise has not been established yet. METHODS: Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross-sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA-Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy- and senescence-related markers. RESULTS: The C. elegans adiponectin receptor PAQR-1/AdipoR1, but not PAQR-2/AdipoR2, was activated (3.55-fold and 3.48-fold increases in p-AMPK on Days 1 and 6, respectively, P < 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29-fold, P < 0.01), muscle weight (1.75-fold, P < 0.001), myonuclei number (1.33-fold, P < 0.05), muscle fibre CSA (1.39-fold, P < 0.05) and capillary abundance (2.19-fold, P < 0.001 for capillary density; 1.58-fold, P < 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94-fold, P < 0.001) and mRNA levels (1.70-fold, P < 0.001) of p16INK4a , a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA-Seq analysis revealed that several KEGG pathways, such as 'AMPK signalling pathway' (P < 0.001), 'FOXO signalling pathway' (P < 0.001) and 'autophagy' (P < 0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise-mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81-fold reduction in LC3-II protein, P < 0.001; 1.53-fold reduction in BNIP3 protein, P < 0.05). Knockdown of daf-16, the FoxO homologue in C. elegans, reduced autophagy (2.77-fold and 2.06-fold reduction in GFP::LGG-1 puncta in seam cells and the intestine, respectively, P < 0.05) and blocked lifespan extension by exercise in worms. CONCLUSIONS: Our findings provide insights into how the AdipoR1 pathway has an impact on the anti-ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age-related loss of skeletal muscle.

A Microbial Community Cultured in Gradient Hydrogel for Investigating Gut Microbiome-Drug Interaction and Guiding Therapeutic Decisions.

Despite the recognition that the gut microbiota acts a clinically significant role in cancer chemotherapy, both mechanistic understanding and translational research are still limited. Maximizing drug efficacy requires an in-depth understanding of how the microbiota contributes to therapeutic responses, while microbiota modulation is hindered by the complexity of the human body. To address this issue, a 3D experimental model named engineered microbiota (EM) is reported for bridging microbiota-drug interaction research and therapeutic decision-making. EM can be manipulated in vitro and faithfully recapitulate the human gut microbiota at the genus/species level while allowing co-culture with cells, organoids, and isolated tissues for testing drug responses. Examination of various clinical and experimental drugs by EM reveales that the gut microbiota affects drug efficacy through three pathways: immunological effects, bioaccumulation, and drug metabolism. Guided by discovered mechanisms, custom-tailored strategies are adopted to maximize the therapeutic efficacy of drugs on orthotopic tumor models with patient-derived gut microbiota. These strategies include immune synergy, nanoparticle encapsulation, and host-guest complex formation, respectively. Given the important role of the gut microbiota in influencing drug efficacy, EM will likely become an indispensable tool to guide drug translation and clinical decision-making.

Comparisons of Cytokines, Growth Factors and Clinical Efficacy between Platelet-Rich Plasma and Autologous Conditioned Serum for Knee Osteoarthritis Management.

This study aimed to directly compare the contents and the clinical efficacy of the two autologous blood-derived products, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) for osteoarthritis (OA) treatment. The contents of standard-prepared PRP and ACS prepared at 37 °C for 1 h, 3 h, 6 h, and 24 h from healthy volunteers were compared. The clinical efficacy of pain relief in patients with Stage III knee OA was evaluated by a patient-reported visual analog scale (VAS) pain rating. PDGF-BB levels in ACS 1 h were significantly higher than those in PRP, and the levels in ACS preparations remained stable. IGF-1 level of ACS 24 h showed a significant increase compared to those of other ACS preparations and PRP. ACS 3 h showed a turning of IL-1Ra level and revealed a time-dependent increase up to 24 h. ACS 6 h showed a turning increase in TNF-α levels. ACS 3 h was chosen for clinical comparison with PRP. The reduction in pain VAS in the ACS group was significantly more compared to those of the PRP group (p = 0.028). However, PRP showed significant earlier improvement (p < 0.001). Conclusion: ACS contained higher levels of PDGF-BB and IL-1Ra and provided better improvement in pain relief compared to PRP.

Analysis of influencing factors associated with the time between cataract surgery and Nd:YAG laser posterior capsulotomy.

PURPOSE: To retrospectively analyze the clinical data of large samples of YAG laser posterior capsulotomy, and to explore the influencing factors of time from cataract surgery to YAG laser capsulotomy (TFCSTLC), so as to provide reference for the occurrence and treatment of real-world posterior capsular opacification (PCO). METHODS: 1093 patients (1093 eyes) with PCO who underwent YAG laser posterior capsulotomy from 2014 to 2019 in the largest eye center of northwest China were analyzed retrospectively. The gender, age, systemic complications, material, and design of intraocular lens (IOL) and TFCSTLC were recorded. The test and Wilcoxon rank sum test were applied to analyze and compare the average TFCSTLC values under different factors, and the relationship between each factor and TFCSTLC was analyzed by multiple linear regression. RESULTS: The average TFCSTLC was 19.2 (range, 7.9 ∼ 31.2) months. There were significant statistical differences in TFCSTLC among the implanted single focus versus multifocal IOLs (P < 0.001), diabetic versus non-diabetic patients (P < 0.001), high myopia versus non-high myopia patients (P = 0.003). Multiple linear regression analysis demonstrated that TFCSTLC was negatively correlated in patients with diabetes mellitus versus with no history of diabetes mellitus (coefficient, -5.36; 95% confidence interval [CI], -8.30 to -2.41; P < 0 .001), and multifocal IOL versus a single focus IOL implanted (coefficient, -5.56 ; 95% CI, -9.01 to -2.11; P = 0.002). CONCLUSIONS: TFCSTLC may be affected by many factors in the real world. The YAG laser posterior capsulotomy time was sooner in patients with a history of diabetes mellitus and multifocal IOL implanted.

High Burden of Premature Ventricular Complex Increases the Risk of New-Onset Atrial Fibrillation.

Background High burden of premature ventricular complex (PVC) leads to increased cardiovascular mortality. A recent nationwide population-based study demonstrated that PVC is associated with an increased risk of atrial fibrillation (AF). However, the relationship between PVC burden and new-onset AF has not been investigated. The purpose of the study is to elucidate whether PVC burden is associated with new-onset AF. Methods and Results We designed a single-center, retrospective, large population-based cohort study to evaluate the role of PVC burden and new-onset AF in Taiwan. Patients who were AF naïve with PVC were divided into the low burden group (<1000/day) and moderate-to-high burden group (≥1000/day) based on the 24-h Holter ECG report. New-onset AF was defined as a new or first detectable event of either a persistent or paroxysmal AF. A total of 16 030 patients who were AF naïve and underwent 24-h Holter ECG monitoring were enrolled in this study, with a mean follow-up time of 973 days. A propensity score-matched analysis demonstrated that the moderate-to-high burden PVC group had a higher risk of developing new-onset AF than that of the low burden PVC group (4.91% versus 2.73%, P<0.001). Multivariate Cox regression analysis showed that moderate-to-high burden of PVC is an independent risk factor for new-onset AF. The Kaplan-Meier analysis demonstrated that patients with moderate-to-high PVC burden were associated with higher risk of new-onset AF (log-rank P<0.001). Conclusions PVC burden is associated with new-onset AF. Patients with moderate-to-high PVC burden are at a higher risk of new-onset AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03877614.

Studies of Mercaptosuccinic Acid-Crosslinked Chitosan Hydrogel with Grafted Cinnamaldehyde and Silver Nanoparticles for Antibacterial Biomedical Application.

For the effective clinical antibacterial application of biomaterials, such as for wound management and tissue repair, the biomaterials need to show proper antibacterial capability as well as non-cytotoxicity. Furthermore, the material needs to have suitable mechanical characteristics for further medical use. Chitosan hydrogel is a potential candidate for various antibacterial biomedical applications due to its amine functionalities that lead to antimicrobial characteristics. Nevertheless, its antimicrobial capability is dependent upon the degree of protonation of amine groups caused by the pH value. Moreover, its mechanical compressive strength may not be high enough for clinical use if not chemically or physically crosslinked. This study utilized a novel chemical crosslinker, mercaptosuccinic acid, to improve its mechanical characteristics. The natural antibacterial agent, cinnamaldehyde, was grafted onto the crosslinked chitosan to improve its antimicrobial capability. Meanwhile, to take advantage of the thiol functionality in the mercaptosuccinic acid, the bactericidal silver nanoparticles were incorporated through silver-thiol covalent bounding. NMR analyses indicated the chitosan was successfully mercaptosuccinic acid-crosslinked and grafted with cinnamaldehyde at different ratios. Combined the results from the mechanical assessment, swelling experiments, antimicrobial assessment, and cytotoxicity assay, the chitosan hydrogel with the highest crosslinked degree and grafted with cinnamaldehyde and silver nanoparticles is of great promise for further clinical uses.

Fabrication of BMP-2-peptide-Deferoxamine- and QK-peptide-functionalized nanoscaffolds and their application for bone defect treatment.

The microenvironment in the healing process of large bone defects requires suitable conditions to promote osteogenesis and angiogenesis. Coaxial electrospinning is a mature method in bone tissue engineering (BTE) and allows functional modification. Appropriate modification methods can be used to improve the bioactivity of scaffolds for BTE. In this study, coaxial electrospinning with QK peptide (a Vascular endothelial growth factor mimetic peptide) and BMP-2 peptide-DFO (BD) was performed to produce double-modified PQBD scaffolds with vascularizing and osteogenic features. The morphology of coaxially electrospun scaffolds was verified by scanning electron microscopy (SEM) and transmission electron microscopy. Laser scanning confocal microscopy and Fourier transform infrared spectroscopy confirmed that BD covalently bound to the surface of the P and PQ scaffolds. In vitro, the PQBD scaffold promoted the adhesion and proliferation of bone marrow stromal cells (BMSCs). Both QK peptide and BD showed sustainable release and preservation of biological activity, enhancing the osteogenic differentiation of BMSCs and the migration of human umbilical vein endothelial cells and promoting angiogenesis. The combined ability of these factors to promote osteogenesis and angiogenesis is superior to that of each alone. In vivo, the PQBD scaffold was implanted into the bone defect, and after 8 weeks, the defect area was almost completely covered by new bone tissue. Histology showed more mature bone tissue and more blood vessels. PQBD scaffolds promote both angiogenesis and osteogenesis, offering a promising approach to enhance bone regeneration in the treatment of large bone defects.