Abstract Magnetic soft materials have been extensively utilized in the development of soft robots. However, they usually fail to achieve programmable soft‐hard magnetic transformations, limiting multimodal magnetoactive deformation and locomotion. Herein, a coaxial magnetic fiber (CMF) consisting of a porous polydimethylsiloxane (p‐PDMS) sheath and a core of sodium alginate sol (SAS) mixed with neodymium‐iron‐boron (NdFeB) particles (NdFeB@SAS) is reported, fabricated using intermittent coaxial 3D printing. The CMF can reversibly transition between a hard magnetic state (coercivity H cm 6900 Oe and remanence M r 61 emu g −1 ) and a soft magnetic state ( H cm 450 Oe and M r 16 emu g −1 ) through the solvent exchange strategy, achieving a ≈15‐fold change in coercivity and a ≈4‐fold increase in remanence. Three CMF‐based samples are constructed and programmed with varying soft‐hard magnetic profiles, exhibiting multimodal magnetoactive deformation. Moreover, under a fluctuating magnetic field, a bionic butterfly robot can flap its wings over a vertical branch without falling. A magnetic brush is also constructed to paint origami objects using magnetic actuation. These demonstrations underscore that the responsiveness of the CMF to global magnetic fields can be locally tailored, allowing for the coexistence of attraction and repulsion in various regions of the CMF, providing a novel approach for developing soft robots.
To obtain a tumor targeting siRNA delivery vehicle for hepatocellular carcinoma treatments, functionalized selenium nanoparticles, Se-PEI-FA, were first prepared by decorating selenium nanoparticles with polycationic polymers, polyethylenimine (PEI), linked with folic acid (FA). FA functions as the tumor-targeted molecule to enhance tumor targeting activity, and PEI conjugates FA and siRNA. Se-PEI-FA@siRNA entered HepG2 cells principally via clathrin-mediated endocytosis. Due to the active tumor targeting effectiveness of FA, Se-PEI-FA@siRNA has significantly higher cellular uptake and gene silencing efficiency, and more apparent cytotoxicity, in HepG2 cells compared with Se-PEI@siRNA. The silencing of HES5 by Se-PEI-FA@siRNA could induce HepG2 cells arrest at G0/G1 phase possibly via inhibiting protein expression of CDK2, cyclinE, and cyclinD1, and up-regulating the protein expression of p21. More importantly, Se-PEI-FA@siRNA exhibits more significant antitumor efficacy compared with Se-PEI@siRNA in vivo. Additionally, Se-PEI-FA@siRNA exhibits low toxicity to the important organs of tumor-bearing mice. This research provides an effective strategy for the design of tumor-targeted nanodrugs against hepatocellular carcinoma.
Abstract The coat of mammals is produced by hair follicles, and hair follicle is an important and complex accessory organ of skin. As a complex physiological regulation process, hair follicle morphogenesis is regulated by a series of signal pathway factors, involves the interaction of multiple cell types and begins in the early embryonic stage. However, its transcriptional regulatory mechanism is unclear. We have therefore utilized single-cell ATAC sequencing to obtain the chromatin accessibility landscapes of 6,928, 6,961 and 7,374 high-quality cells from the dorsal skins of E13.5, E16.5 and P0 mice ( Mus musculus ), respectively. Based on marker gene activity clustering, we defined 6, 8 and 5 distinct cell types in E13.5, E16.5 and P0 stages, respectively. Furtherly, we integrated the fibroblasts and keratinocytes clusters, performed further analysis and re-clustered. The single cell map of the chromatin open area was drawn from each cell type and the mechanism of cell transcription regulation was explored. Collectively, our data provide a reference for deeply exploring the epigenetic regulation mechanism of mouse hair follicles development.
Abstract Background : To evaluate whether oral lichen planus (OLP) is a risk factor for peri-implant diseases (PIDs) with a systematic review and meta-analysis. Methods : Six electronic databases including Medline, Web of Science, etc. were searched. Included studies are observational human studies written in English. Population of interest were those with/without OLP who received dental implant treatment. Follow-up time after implantation is from one month to 20 years. The quality of the included literature regarding risk of bias and methodology was assessed with Newcastle-Ottawa Scale or the Agency for Healthcare Research and Quality. The data involving exposure (OLP), primary outcomes (implants having PIDs) and secondary outcomes (probing depth/PD, bleeding on probing/BOP and bone loss/BL) and potential confounders were extracted. Heterogeneity was assessed by I² tests. Dichotomous data were expressed as risk ratio (RR) and 95% confidence interval (CI) which were calculated with a fixed effect model. Results : Of 139 literatures, two studies were enrolled and evaluated as high quality, which totally contained 68 participants receiving 222 (OLP vs. non-OLP, 112 vs. 110) implants with 12 to 120-month follow-up time. Proportions of implants with PIDs between OLP and non-OLP groups were as follows: 19.6% (22/112) vs. 22.7% (25/110) for PIM; 17.0% (19/112) vs. 10.9% (12/110) for PI. Meta-analysis found no recognizable difference in number of implants with PIDs (PI: RR = 1.49, 95% CI 0.77-2.90, P = 0.24; PIM:RR = 0.88, 95% CI 0.53 -1.46, P = 0.61; PIDs: RR = 1.08, 95% CI 0.75 -1.55, P = 0.68) or BOP (RR = 0.90, 95% CI: 0.70-1.15, P = 0.40) between OLP and non-OLP groups. Conclusions : Available literature regarding the effects of OLP on PIDs remains very limited. Existing evidence seems not support OLP as a suspected risk factor for PIDs. Large-scale prospective trials are required to test the findings. Keywords : dental implants; peri-implant diseases; oral lichen planus; systematic review; meta-analysis.
To develop and internally validate a nomogram to predict the risk of death within 6 months of onset of stroke in Chinese. Identifying risk factors with potentially direct effects on the nomogram will improve the quality of risk assessment and help nurses implement preventive measures based on patient-specific risk factors.A retrospective study.We performed a least absolute shrinkage and selection operator (LASSO) regression modelling and multivariate logistic regression analysis to establish a prediction model of death risk in stroke patients within 6 months of onset. LASSO and time-dependent Cox regression models were further used to analyse the 6-month survival of stroke patients. Data were collected from 21 October 2013-6 May 2019.The independent predictors of the nomogram were Barthel index (odds ratio (OR) = 0.980, 95% confidence interval (CI) = 0.961-0.998, p = .03), platelet/lymphocyte ratio (OR = 1.005, 95% CI = 1.000-1.010, p = .04) and serum albumin (OR = 0.854, 95% CI = 0.774-0.931, p < .01). This model showed good discrimination and consistency, and its discrimination evaluation C-statistic was 0.879 in the training set and 0.891 in the internal validation set. The DCA indicated that the nomogram had a higher overall net benefit over most of the threshold probability range. The time-dependent Cox regression model established the impact of the time effect of the age variable on survival time.Our results identified three predictors of death within 6 months of stroke in Chinese. These predictors can be used as risk assessment indicators to help caregivers performing clinical nursing work, and in clinical practice, it is suggested that nurses should evaluate the self-care ability of stroke patients in detail. The constructed nomogram can help identify patients at high risk of death within 6 months, so that intervention can be performed as early as possible.
Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data.This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors.A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of<20 mL/min), cardiovascular diseases, and digestive system diseases were independent risk factors for poor clinical efficacy of CAZ/AVI-based regimens. Bloodstream infection (BSI), patients with the adjusted doses of CAZ/AVI, and CAZ/AVI co-administration with carbapenem were independently associated factors of bacterial clearance by CAZ/AVI-based regimens. Age, total hospital stays, use of mechanical ventilation, and cumulative CAZ/AVI dose were independent factors associated with all-cause mortality.CAZ/AVI was an effective drug in treating CR-GNB infection. CAZ/AVI that is mostly excreted by the kidney and is accumulated in renal impairment should be renally adjusted. Renal dysfunction and the adjusted dose of CAZ/AVI were associated with efficacy. Clinicians should individualize CAZ/AVI regimen and dose by the level of renal function to achieve optimal efficacy and survival. The efficacy of CAZ/AVI in the treatment of CR-GNB infection, as well as the implementation of individualized precision drug administration of CAZ/AVI according to patients' different infection sites, renal function, bacterial types, bacterial resistance mechanisms, blood concentration monitoring and other conditions need to be further studied in multicenter.
As an effective antiviral agent, the clinical application of oseltamivir (OTV) is limited by the appearance of drug-resistant viruses. Due to their low toxicity and excellent activity, the antiviral capabilities of selenium nanoparticles (SeNPs) has attracted increasing attention in recent years. To overcome the limitation of drug resistance, the use of modified NPs with biologics to explore novel anti-influenza drugs is developing rapidly. In this study, OTV surface-modified SeNPs with superior antiviral properties and restriction on drug resistance were synthesized. OTV decoration of SeNPs (Se@OTV) obviously inhibited H1N1 infection and had less toxicity. Se@OTV interfered with the H1N1 influenza virus to host cells through inhibiting the activity of hemagglutinin and neuraminidase. The mechanism was that Se@OTV was able to prevent H1N1 from infecting MDCK cells and block chromatin condensation and DNA fragmentation. Furthermore, Se@OTV inhibited the generation of reactive oxygen species and activation of p53 phosphorylation and Akt. These results demonstrate that Se@OTV is a promising efficient antiviral pharmaceutical for H1N1.
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