Switchable Power Generation in Triboelectric Nanogenerator Toward Chip-Less Wearable Power Module Applications.

A conceptual shift toward next-generation wearable electronics is driving research into self-powered electronics technologies that can be independently operated without plugging into the grid for external power feeding. Triboelectric nanogenerators (TENGs) are emerging as a key component of self-powered electronics, but a power type mismatch between supply and demand limits their direct implementation into wearable self-powered electronics. Here, a TENG with switchable power mode capability is reported where the charge flow direction is modulated over the course of slow and random mechanical stimuli, with exceptional rectification capabilities as high as ≈133, stable outputs over the cycles, and design flexibility in different platforms. Importantly, the remarkable switchable power generation with fabric counter materials illuminates a new path for the smooth integration of flexible TENGs into wearable self-powered electronics.

Encapsulation of Monodisperse Microdroplets in Nanofibers through a Microfluidic-Electrospinning Hybrid Method.

Fibers with droplets encapsulated in them could build bridges between a 0D dispersed structure and a 1D continuous wire and thus provide optimal solutions requiring high surface-to-volume ratio and strong mechanical properties. However, current methods are mostly focusing on the architectures with the size of droplets smaller than that of fibers; the relatively thick barrier of fibers usually limits the rate of diffusion from inner droplets to the outer environment. Here, we report a hybrid method combining microfluidics and electrospinning to fabricate nanofibers with microdroplets encapsulated in them. Monodisperse microdroplets with controllable sizes from 36 to 95 µm are generated through microfluidic flow-focusing and split into a string of smaller droplets from 1 to 3 µm, respectively, during the electrospinning stretching. The size of encapsulated droplets could be tuned by controlling the flow rate ratio during the microfluidic process, and the shape of that could be varied by changing the viscosity of encapsulated solution. This marriage of microfluidics and electrospinning could be applied to produce a nanofiber-based moisture barrier and drug carrier, also providing efficient tools to study the under-electric-field stretching and splitting of droplets trapped in the polymer network.

Safety and efficacy of irinotecan, oxaliplatin, and capecitabine (XELOXIRI) regimen with or without targeted drugs in patients with metastatic colorectal cancer: a retrospective cohort study.

BACKGROUND: Five-fluorouracil, folinic acid, oxaliplatin and irinotecan (FOLFOXIRI) regimen is used as the first-line treatment for metastatic colorectal cancer (mCRC). The use of capecitabine, an oral fluoropyrimidine pro-drug, is feasible and safe; hence, it provides an interesting alternative to 5-fluorouracil in the abovementioned regimen. This study aimed to evaluate the efficacy and safety of capecitabine, oxaliplatin, and irinotecan (XELOXIRI) regimen use with or without targeted drugs in Chinese patients with mCRC. METHODS: We conducted a retrospective, longitudinal cohort study of patients with mCRC who received XELOXIRI regimen with or without targeted drugs (bevacizumab or cetuximab) every 2 weeks between January 2017 and November 2019 at the National Cancer Center/Cancer Hospital, the Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment efficacy was assessed by investigators by evaluating the objective response rate (ORR) and disease control rate (DCR). Overall survival (OS) was assessed using Cox proportional hazards models. The adverse events were also analyzed. RESULTS: Sixty-one consecutive patients were examined and followed up for survival. As of November 8, 2021, the median follow-up time was 35.4 months. Disease progression and death occurred in 50 (82%) and 38 (62%) patients, respectively. The median treatment duration of XELOXIRI with or without bevacizumab or cetuximab was 10 cycles (range, 1-12 cycles). The median OS and PFS were 32.2 months (95%CI [24.8-39.6]) and 9.3 months (95% CI [8.1-10.5]), respectively. The ORR of 48 patients with measurable lesions was 70.8%, and the DCR was 89.6%. RAS/BRAF wild-type (HR 0.39; 95% CI [0.16-0.96], p = 0.04) and metastatic organs > 2 (HR 3.25; 95% CI [1.34-7.87], p = 0.009) were independent prognostic factors for OS. The incidence of any grade of adverse events (AEs) was 96.7% (59/61). Grade ≥ 3 AEs included neutropenia (19.7%), leukopenia (9.8%), diarrhea (3.3%), vomiting (3.3%), febrile neutropenia (1.6%), and thrombocytopenia (1.6%). No treatment-related death occurred. CONCLUSION: The use of the XELOXIRI regimen with or without a targeted drug was effective, with a manageable toxicity profile in Chinese patients with mCRC.

Blood biomarkers of bone metastasis in digestive tract malignant tumors.

Aim: To evaluate the role of clinical features and blood markers in patients with malignant digestive tract tumors bone metastasis. Materials & methods: A total of 267 patients were included in this trial. Age, gender, primary tumor site, metastatic sites, T/N stage, high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, alkaline phosphatase, LDH, Ca levels, platelet, neutrophils to absolute value of lymphocytes (NLR), ratio of platelets to absolute values of lymphocytes (PLR) were analyzed. Results: T stage, lymph node metastasis, N stage and liver and lung metastasis were independent risk factors. LDH + alkaline phosphatase + NLR + PLR and LDH + NLR, respectively have higher predictive value for bone metastasis compared with patients with early-stage malignant digestive tract tumor and patients with advanced malignant digestive tract tumor without bone metastasis. Conclusion: Some clinical features or blood markers have the potential to detect bone metastasis early to avoid skeletal complications.

Graph-based multi-user scheduling for indoor cooperative visible light transmission.

Recent progress in the indoor visible light communication (VLC) has shown promising signs of alleviating an increasing strain on the radio frequency spectrum and enhancing transmission capacity. Nevertheless, the indoor VLC usually suffers from inter-channel interference (ICI) due to the dense light-emitting diode (LED) deployment. The ICI is considered as a key factor affecting signal to interference and noise ratio (SINR) and spectral efficiency. To address this challenge, an efficient multi-user scheduling framework that employs interference coordination and cooperative transmission is investigated based on the graph theory. To effectively mitigate ICI and maximize benefit of the cooperative transmission, the cell-centric (CC) and user-centric (UC) clustering are introduced for cooperative transmission. For the CC clustering, the multi-user scheduling problem under the proportional fairness criterion is formulated to maximize spectral efficiency while ensuring user fairness. Such a problem is solved by linear programming and greedy algorithms after transforming it into a maximum weighted independent set problem with the aid of a modified interference graph. For the UC clustering, the multi-user scheduling problem under the max-min criterion is formulated and solved by a proposed heuristic approach based on the bipartite graph theory. Numerical results show that the proposed graph-based scheduling is capable of providing up to 7.7 dB gain in SINR over the non-cooperative transmission. The bipartite graph scheduling offers high spectral efficiency and service fairness index. In the worst case with an occlusion probability of 1, a small SINR penalty of up to 1 dB is observed with the greedy algorithm. It is shown that the graph-based scheduling is robust to receiver rotation and occlusion in terms of spectral efficiency, SINR, and user fairness.

Recommendations in clinical practice guidelines on gout: systematic review and consistency analysis.

OBJECTIVES: To compare and analyse the recommendations from clinical practice guidelines (CPGs) on gout worldwide, examine the consistency across CPGs, and provide suggestions to develop and update gout guidelines. METHODS: We conducted systematic searches in MEDLINE, CBM, GIN, NICE, NGC, WHO, SIGN, DynaMed, UpToDate, and Best Practice databases, from their inception to August 2019 to identify and select CPGs related to gout. We used the search terms "gout", "hyperuricaemia" and "guideline". After two rounds of screening, we included the eligible CPGs of gout according to the pre-defined inclusion and exclusion criteria. Methodological quality of included guidelines was assessed with the AGREE-II instrument. The general characteristics of included guidelines and the recommendations were extracted, and the consistency of recommendations across guidelines was compared and analysed. RESULTS: A total of 15 gout guidelines including 359 recommendations were retrieved. The main topics covered by the recommendations were diagnosis, pharmacologic treatment of gout flares, pharmacologic urate-lowering therapy (ULT) of chronic gouty arthritis, lifestyle interventions, prophylaxis, and management of asymptomatic hyperuricaemia. The results of AGREE-II appraisal showed that only two guidelines achieved high scores (≥50%) in all six domains. There was substantial discrepancy between the guidelines in recommendations covering the value of computed tomography (CT) and x-rays for diagnosis, the use of corticosteroids as a first-line treatment for flare, the use of colchicine, indications for ULT, the use of febuxostat as first-line ULT, the administration of allopurinol, and the timing of ULT initiation. CONLUSIONS: A number of countries are devoting themselves to the development of gout guidelines, but the process of updating guidelines is slower than that suggested by the WHO. Methodological quality is not satisfactory in most guidelines, and recommendations between guidelines are not consistent.

Bacterial Cellulose: A Versatile Chiral Host for Circularly Polarized Luminescence.

Materials capable of circularly polarized luminescence (CPL) have attracted considerable attention for their promising potential applications. Bacterial cellulose (BC) was characterized as having a stable right-handed twist, which makes it a potential chiral host to endow luminophores with CPL. Then, the CPL-active BC composite film was constructed by simply impregnating bacterial cellulose pellicles with dilute aqueous solutions of luminophores (rhodamine B, carbon dots, polymer dots) and drying under ambient conditions. Simple encapsulation of luminophores renders BC with circularly polarized luminescence with a dissymmetry factor of up to 0.03. The multiple chiral centers of bacterial cellulose provide a primary asymmetric environment that can be further modulated by supramolecular chemistry, which is responsible for its circular polarization ability. We further demonstrate that commercial grade paper may endow luminophores with CPL activity, which reifies the universality of the method.

The Phenylethanol Glycoside Liposome Inhibits PDGF-Induced HSC Activation via Regulation of the FAK/PI3K/Akt Signaling Pathway.

Cistanche tubulosa is a traditional Chinese herbal medicine that is widely used to regulate immunity, and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. However, the application of CPhGs is negatively affected by their poor absorption and low oral utilization. Targeted drug delivery is an important development direction for pharmaceutics. Previous studies have indicated that CPhGs could block the conduction of the signaling pathways in TGF-ß1/smad and inhibit the activation of hepatic stellate cells (HSCs). The aim of this study was to evaluate the anti-hepatic fibrosis effect of CPhG liposomes by inhibiting HSC activation, promoting apoptosis, blocking the cell cycle, suppressing the conduction of signaling pathways in focal adhesion kinase(FAK)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), and determining their in vitro hepatoprotective activity. In vitro release studies demonstrated that CPhG liposomes have a sustained release effect compared to drug CPhGs. HSC proliferation was inhibited after treatment with the CPhG liposomes (29.45, 14.72, 7.36 µg/mL), with IC50 values of 42.54 µg/mL in the MTT assay. Different concentrations of the CPhG liposomes could inhibit HSC proliferation, promote apoptosis, and block the cell cycle. The MTT method showed an obvious inhibition of HSC proliferation after CPhG liposome and Recombinant Rat Platelet-derived growth factor-BB(rrPDGF-BB) treatment. The levels of collagen-1, metallopeptidase inhibitor 1 (TIMP-1), α smooth muscle actin (α-SMA), and phosphorylated PI3K/Akt were downregulated, and matrix metalloproteinase-1 (MMP-1) was upregulated, by pretreatment with different concentrations of CPhG liposomes. Moreover, 29.45 µg/mL of CPhG liposomes could decrease the expression of the FAK protein and the phosphorylated PI3K and Akt protein downstream of FAK by overexpression of the FAK gene. This experiment suggests that CPhG liposomes may inhibit the activation of HSCs by inhibiting FAK and then reducing the expression of phosphorylated Akt/PI3K, thereby providing new insights into the application of CPhGs for liver fibrosis.

Synergistic Chemical Synthesis and Self-Assembly Lead to Three-Dimensional b-Oriented MFI Superstructures with Selective Adsorption and Luminescence Properties.

Higher-order organization of inorganic nanoparticles with hierarchical architectures and tailored functionality is crucial in the nanofabrication of advanced materials. Here we demonstrate that three-dimensional b-oriented MFI superstructures can be organized by synergistic chemical synthesis and self-assembly. The organization is accomplished by vapor treatment of tetrapropylammonium hydroxide (TPAOH)-coated inorganic/bacterial cellulose scaffolds. TPA+ acts to direct nucleation and to mediate crystal morphology leading to oriented assembly of MFI crystals along crystallographic b-axis, whereas bacterial cellulose holds the oriented assembly together forming three-dimensional superstructures with macroporosity. Self-supporting monoliths of the macroporous MFI show outstanding selective adsorption for para-xylene and high adsorption capacity for volatile organic compounds. Incorporating luminescent molecules imparts the macroporous monoliths the new property of adsorption tunable luminescence that may act as an optical sensor indicating the level of adsorption. The current work opens a novel space for rational organization of hierarchical materials with tailored architectures and multifunctionality.

Spondin 1 promotes metastatic progression through Fak and Src dependent pathway in human osteosarcoma.

Spondin 1 (SPON1) is cell adhesion protein that involved in attachment of sensory neuron cells and outgrowth of neurites. Its cellular functions and related mechanisms in cancers, however, remain largely unexplored. In this study, we first identified that SPON1 acts a critical factor in the metastatic progression of osteosarcoma through analysis of a GEO dataset. Then we demonstrated that SPON1 was significantly up-regulated in 72 osteosarcoma specimens compared with benign osteochondroma samples and elevated SPON1 was positively correlated with MMP9 expression. Knockdown of SPON1 expression in two metastatic osteosarcoma cell lines, HKOS and KRIB, dramatically suppressed cell migration and invasion. Treatment with recombinant SPON1 protein in two non-metastatic osteosarcoma cell lines, HOS and U2OS, significantly promoted cell migration and invasion in vitro. Meanwhile, suppression of SPON1 in KHOS cells resulted in decreased pulmonary metastasis in vivo. Mechanistically, we determined that the effects of SPON1 on osteosarcoma cell motility were primarily mediated through Fak and Src dependent pathway. Taken together, our study provides evidence of the contributions of SPON1 and the Fak and Src signaling to the progression of osteosarcoma and suggests that this axis may represent a potential therapeutic target for osteosarcoma.

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer.

BACKGROUND: Treatment options for patients with gastric cancer (GC) continue to improve, but the overall prognosis is poor. The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present, and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups. AIM: To determined the effects of differentially expressed immune-related genes (DEIRGs) on the development, prognosis, tumor microenvironment (TME), and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations. METHODS: Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas (TCGA), and immune-related genes (IRGs) were searched from ImmPort. DEIRGs were extracted from the intersection of the differentially-expressed genes (DEGs) and IRGs lists. The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes (KEGGs) and Gene Ontology (GO) databases. To identify genes associated with prognosis, a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression. The tumor risk score was divided into high- and low-risk groups. The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model. The infiltration of immune cells was obtained using 'CIBERSORT,' and the infiltration of immune subgroups in high- and low-risk groups was analyzed. The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed. RESULTS: We collected 412 GC and 36 adjacent tissue samples, and identified 3627 DEGs and 1311 IRGs. A total of 482 DEIRGs were obtained. GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes, receptor ligand activity, and signaling receptor activators. KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors, neuroactive ligand receptor interactions, and viral protein interactions. We ultimately obtained an immune-related signature based on 10 genes, including 9 risk genes (LCN1, LEAP2, TMSB15A mRNA, DEFB126, PI15, IGHD3-16, IGLV3-22, CGB5, and GLP2R) and 1 protective gene (LGR6). Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, and risk curves confirmed that the risk model had good predictive ability. Multivariate COX analysis showed that age, stage, and risk score were independent prognostic factors for patients with GC. Meanwhile, patients in the low-risk group had higher tumor mutation burden and immunophenotype, which can be used to predict the immune checkpoint inhibitor response. Both cytotoxic T lymphocyte antigen4+ and programmed death 1+ patients with lower risk scores were more sensitive to immunotherapy. CONCLUSION: In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME. By providing risk factor analysis and prognostic information, our risk model can provide new directions for immunotherapy in GC patients.

Efficacy and adverse events of immune checkpoint inhibitors in esophageal cancer patients: Challenges and perspectives for immunotherapy.

Esophageal cancer (EC) is the seventh most common cancer worldwide. Patients with EC have a generally poor prognosis mainly due to the lack of effective treatments. Cancer immunotherapy is a promising novel treatment option for EC. This literature review investigated the clinical efficacy of immunotherapy either alone or in combination with chemotherapy or targeted therapy. In addition, we analyzed the adverse events associated with immune checkpoint inhibitors (ICIs). In conclusion, ICIs increase the efficacy of EC treatments, thereby improving the outcomes of EC patients. The findings of this study may help enhance the response to immunotherapy, diminish toxicity, and thus eventually improve medical care for patients with EC.

PROTOCOL: Effectiveness of behavioral interventions for smoking cessation among homeless persons: A systematic review and meta-analysis.

This is the protocol for an updated Campbell systematic review. The objectives are as follows: To evaluate the effect of behavioral interventions on smoking cessation among homeless individuals.

Significant effect of posterior line treatment of HER2 positive advanced gastric cancer: A case report.

At present, there are few options for third line and above treatment of advanced gastric cancer and the single drug effect is poor. HER2 positive gastric cancer is an important subtype of gastric cancer and has certain immune characteristics. The combination of HER2 inhibitor and PD-1 inhibitor has a synergistic effect, and anti-tumor drugs targeting HER2 can play an anti-angiogenesis role by downregulating VEGF. We report a patient with HER2-positive gastric cancer who developed post-operative tumor recurrence and metastasis after adjuvant chemotherapy and radiotherapy. Trastuzumab combined with albumin paclitaxel was used as second-line treatment with progression-free survival for 9 months. In third line treatment, we retained trastuzumab and combined it with camrelizumab and apatinib. During the treatment period, although the patient stopped taking the drugs due to the side effects of camrelizumab and apatinib, he achieved a PFS of 10.4 months. Considering the good effect of the third line treatment, we added another PD-1 inhibitor and continued to combine trastuzumab treatment. We found that the patient still benefited from the treatment and continued to survive for another 4 months. At present, the patient is treated with DisitamabVedotin (HER2-ADC) combined with PD-1 inhibitor, and no overall survival outcome has been observed.

Overview of the interplay between m6A methylation modification and non-coding RNA and their impact on tumor cells.

N6-methyladenosine (m6A) is one of the most common internal modifications in eukaryotic RNA. The presence of m6A on transcripts can affect a series of fundamental cellular processes, including mRNA splicing, nuclear transportation, stability, and translation. The m6A modification is introduced by m6A methyltransferases (writers), removed by demethylases (erasers), and recognized by m6A-binding proteins (readers). Current research has demonstrated that m6A methylation is involved in the regulation of malignant phenotypes in tumors by controlling the expression of cancer-related genes. Non-coding RNAs (ncRNAs) are a diverse group of RNA molecules that do not encode proteins and are widely present in the human genome. This group includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI interaction RNAs (piRNAs). They function as oncogenes or tumor suppressors through various mechanisms, regulating the initiation and progression of cancer. Previous studies on m6A primarily focused on coding RNAs, but recent discoveries have revealed the significant regulatory role of m6A in ncRNAs. Simultaneously, ncRNAs also exert their influence by modulating the stability, splicing, translation, and other biological processes of m6A-related enzymes. The interplay between m6A and ncRNAs collectively contributes to the occurrence and progression of malignant tumors in humans. This review provides an overview of the interactions between m6A regulatory factors and ncRNAs and their impact on tumors.

Development and validation of a novel prediction model for Carbapenem-resistant organism infection in a large-scale hospitalized patients.

Carbapenem-resistant organism (CRO) are defined as gram-negative bacteria. The lack of safe and effective antibiotics has led to an increase in incidence rate. The purpose of this study is to establish and determine a risk nomogram to predict CRO infection in hospitalized patients. Hospitalized patients' information were collected from the electronic medical record system of hospital between January 2019 and December 2022. Based on the inclusion and exclusion criteria, we identified 131390 inpatients who met the criteria for this study. For the training cohort, the area under the curves (AUC) for predicting the CRO infection was 0.935. For the validation cohort, the AUC for predicting the CRO infection was 0.937. We have developed the first novel nomogram to predict CRO infection in hospitalized patients, which is reliable and high-performance. The nomogram performs well among hospitalized patients and has good predictive ability.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer.

BACKGROUND: Although treatment options for gastric cancer (GC) continue to advance, the overall prognosis for patients with GC remains poor. At present, the predictors of treatment efficacy remain controversial except for high microsatellite instability. AIM: To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1 (PD-1) inhibitor and chemotherapy. METHODS: We acquired data from 63 patients with human epidermal growth factor receptor 2 (HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital, Chinese Academy of Medical Sciences between November 2020 and October 2022. All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment. RESULTS: As of July 1, 2023, the objective response rate was 61.9%, and the disease control rate was 96.8%. The median progression-free survival (mPFS) for all patients was 6.3 months. The median overall survival was not achieved. Survival analysis showed that patients with a combined positive score (CPS) ≥ 1 exhibited an extended trend in progression-free survival (PFS) when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment. PFS exhibited a trend for prolongation as the expression level of HER2 increased. Based on PFS, we divided patients into two groups: A treatment group with excellent efficacy and a treatment group with poor efficacy. The mPFS of the excellent efficacy group was 8 months, with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery. The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery. Using good/poor efficacy as the endpoint of our study, univariate analysis revealed that both CPS score (P = 0.004) and HER2 expression level (P = 0.015) were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC (AGC). Finally, multivariate analysis confirmed that CPS score was a significant influencing factor. CONCLUSION: CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

Bridging Reduced Grip Strength and Altered Executive Function: Specific Brain White Matter Structural Changes in Patients with Alzheimer's Disease.

Objective: To investigate the correlation between specific fiber tracts and grip strength and cognitive function in patients with Alzheimer's disease (AD) by fixel-based analysis (FBA). Methods: AD patients were divided into AD with low grip strength (AD-LGS, n=29) and AD without low grip strength (AD-nLGS, n=25), along with 31 normal controls (NC). General data, neuropsychological tests, grip strength and cranial magnetic resonance imaging (MRI) scans were collected. FBA evaluated white matter (WM) fiber metrics, including fiber density (FD), fiber cross-sectional (FC), and fiber density and cross-sectional area (FDC). The mean fiber indicators of the fiber tracts of interest (TOI) were extracted in cerebral region of significant statistical differences in FBA to further compare the differences between groups and analyze the correlation between fiber properties and neuropsychological test scores. Results: Compared to AD-nLGS group, AD-LGS group showed significant reductions in FDC in several cerebral regions. In AD patients, FDC values of bilateral uncinate fasciculus and left superior longitudinal fasciculus were positively correlated with Clock Drawing Test scores, while FDC of splenium of corpus callosum, bilateral anterior cingulate tracts, forceps major, and bilateral inferior longitudinal fasciculus were positively correlated with the Executive Factor Score of Memory and Executive Screening scale scores. Conclusion: Reduced grip strength in AD patients is associated with extensive impairment of WM structural integrity. Changes in FDC of specific WM fiber tracts related to executive function play a significant mediating role in the reduction of grip strength in AD patients.

Accelerated Selective Li+ Transports Assisted by Microcrack-Free Anionic Network Polymer Membranes for Long Cyclable Lithium Metal Batteries.

Rechargeable Li metal batteries have the potential to meet the demands of high-energy density batteries for electric vehicles and grid-energy storage system applications. Achieving this goal, however, requires resolving not only safety concerns and a shortened battery cycle life arising from a combination of undesirable lithium dendrite and solid-electrolyte interphase formations. Here, a series of microcrack-free anionic network polymer membranes formed by a facile one-step click reaction are reported, displaying a high cation conductivity of 3.1 × 10-5 S cm-1 at high temperature, a wide electrochemical stability window up to 5 V, a remarkable resistance to dendrite growth, and outstanding non-flammability. These enhanced properties are attributed to the presence of tethered borate anions in microcrack-free membranes, which benefits the acceleration of selective Li+ cations transport as well as suppression of dendrite growth. Ultimately, the microcrack-free anionic network polymer membranes render Li metal batteries a safe and long-cyclable energy storage device at high temperatures with a capacity retention of 92.7% and an average coulombic efficiency of 99.867% at 450 cycles.

DNMT3A-mediated epigenetic silencing of SOX17 contributes to endothelial cell migration and fibroblast activation in wound healing.

BACKGROUND: Wound healing, especially impaired chronic wound healing, poses a tremendous challenge for modern medicine. Understanding the molecular mechanisms underlying wound healing is essential to the development of novel therapeutic strategies. METHODS: A wound-healing mouse model was established to analyze histopathological alterations during wound healing, and the expression of SRY-box transcription factor 17 (SOX17), DNA methyltransferase 3 alpha (DNMT3A), and a specific fibroblast marker S100 calcium-binding protein A4 (S100A4) in wound skin tissues was tested by immunofluorescence (IF) assay. Cell proliferation and migration were evaluated using 5-ethynyl-2'-deoxyuridine (EdU) and Transwell migration assays. RT-qPCR and western blotting were used to measure RNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion of transforming growth factor-beta (TGF-ß). Chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) and DNA pull-down assays were performed to confirm the interaction between DNMT3A and the CpG island of the SOX17 promoter. Promoter methylation was examined by pyrosequencing. RESULTS: SOX17 and DNMT3A expression were regularly regulated during the different phases of wound healing. SOX17 knockdown promoted HUVEC migration and the production and release of TGF-ß. Through establishing an endothelial cells-fibroblasts co-culture model, we found that SOX17 knockdown in HUVECs activated HFF-1 fibroblasts, which expressed α-smooth muscle actin (α-SMA) and type I collagen (COL1). DNMT3A overexpression reduces SOX17 mRNA levels. ChIP-qPCR and DNA pull-down assays verified the interaction between DNMT3A and CpG island in the SOX17 promoter region. Pyrosequencing confirmed that DNMT3A overexpression increased the methylation level of the SOX17 promoter. CONCLUSION: DNMT3A-mediated downregulation of SOX17 facilitates wound healing by promoting endothelial cell migration and fibroblast activation.