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Electronic textiles have been regarded as the basic building blocks for constructing a new generation of wearable electronics. However, the electronization of textiles often changes their original properties such as color, softness, glossiness, or flexibility. Here a rapid room‐temperature fabrication method toward conductive colorful threads and fabrics with Ag‐coated Cu (Cu‐Ag) nanonets is demonstrated. Cu–Ag core–shell nanowires are produced through a one‐pot synthesis followed by electroless deposition. According to the balance of draining and entraining forces, a fast dip‐withdraw process in a volatile solution is developed to tightly wrap Cu–Ag nanonets onto the fibers of thread. The modified threads are not only conductive, but they also retain their original features with enhanced mechanical stability and dry‐wash durability. Furthermore, various e‐textile devices are fabricated such as a fabric heater, touch screen gloves, a wearable real‐time temperature sensor, and warm fabrics against infrared thermal dissipation. These high quality and colorful conductive textiles will provide powerful materials for promoting next‐generation applications in wearable electronics. [ABSTRACT FROM AUTHOR]

The Zoige Depression is an important depocenter zone within the northeast of the Songpan-Ganzi Flysch Basin, which is bounded by the South China, North China, and Qiangtang blocks, and also forms the northeastern margin of Tibetan Plateau. This paper discusses the provenance of Middle to Late Triassic sedimentary rocks in the Zoige Depression using petrography, heavy mineral assemblages, and zircon U-Pb geochronology. The results demonstrate that the detritus is derived from multiple source regions. Four distinct parent rocks can be distinguished based on the heavy mineral assemblages and lithic fragments: Provenance 1 predominantly comprises intermediate-acidic volcanic rocks; Provenance 2 includes high-grade metamorphic rocks; Provenance 3 contains a mixture of various detrital components; and Provenance 4 primarily consists of mafic volcanic rocks. The different U-Pb ages of the zircons from the Middle to Late Triassic ranging from 260 to 280, 429-480, 792-974, and 1,800-2,500 Ma represent distinct source regions, which are comparable to the 4 provenances mentioned above: Provenance 1 (260-280 Ma), Eastern Kunlun Orogen; Provenance 2 (429-480 and/or 1,800-2,500 Ma), Qinling orogeny (mainly in North Qinling); Provenance 3 (1,800-2,500 Ma), the North China Block; and Provenance 4 (792-974 Ma), the Yangtze Block. Overall, the detritus in the Middle Triassic (Ladinian, T2zg) primarily originates from the Eastern Kunlun Orogen and North Qinling. During the Late Triassic (Early Carnian, T3z), the southern margin of the North China Block was likely transported westward to the basin by a river network between the North China and South China blocks flowing through the Qinling region, because of the predominance of the detrital zircon age ranging from 1,800 to 2,500 Ma and the occurrence of quartz sandstone with visible enlargement texture. Since the Late Triassic (Middle Carnian, T3zh), great changes have occurred in the source terrains, such as the absence of sources of the Eastern Kunlun Orogen and North China Block and the predominance of Yangtze Block. This drastic change can be explained by the Triassic collision between the South China and North China blocks, and the clockwise rotation of the South China Block progressively closed the basin and uplifted the Qinling orogeny. [ABSTRACT FROM AUTHOR]

Reasonable regulation of iodine redox has gradually shown potential as a desirable cathodic reaction in zinc‐based batteries, but suffers from poor cyclic reversibility caused by uncontrollable side reactions. Also, the irregular growth of dendrites and unavoidable occurrences of hydrogen evolution reaction in H2O‐rich environment have become permanent topics in anodic zinc. Herein, a cross‐linked gel based on carboxymethyl chitosan is proposed and serves as an artificial electrolyte interphase for zinc anode (marked as Zn‐CMCS). Such a coating formed by crosslinking among a monodentate carboxyl group, a hydroxyl, an amino, and Zn2+ from adding solution closely adheres on the surface of the zinc foil with toughness, ductility, and ideal electrochemical kinetics. Additionally, its homogenized surface charge distribution provides a "flexible" substrate for zinc plating/stripping, resulting in a flat real‐time interface. While introducing I−/I0 conversion by matching adsorptive activated carbon on carbon fiber cloth (AC‐CFC) as cathode, the internal space restricted by CMCS gel enables the assembled Zn‐CMCS/AC‐CFC battery to exhibit a greatly improved reversibility under long‐cycling condition within 28 000 cycles (measured for more than 2 years) in a narrow operating voltage range of 0.23 V. [ABSTRACT FROM AUTHOR]

Objective: To characterize the phenotype spectrum, diagnosis, and response to growth‐promoting therapy in patients with ACAN variants causing familial short stature. Methods: Three families with ACAN variants causing short stature were reported. Similar cases in the literature were summarized, and the genotype and phenotype were analyzed. Results: Three novel heterozygous variants, c.757+1G>A, (splicing), c.6229delG, p.(Asp2078Tfs*1), and c.6679C>T, p.(Gln2227*) in the ACAN gene were identified. A total of 314 individuals with heterozygous variants from 105 families and 8 individuals with homozygous variants from 4 families were confirmed to have ACAN variants from literature and our 3 cases. Including our 3 cases, the variants reported comprised 33 frameshift, 39 missense, 23 nonsense, 5 splicing, 4 deletion, and 1 translocation variants. Variation points are scattered throughout the gene, while exons 12, 15, and 10 were most common (25/105, 11/105, and 10/105, respectively). Some identical variants existing in different families could be hot variants, c.532A>T, p.(Asn178Tyr), c.1411C>T, p.(Gln471*), c.1608C>A, p.(Tyr536*), c.2026+1G>A, (splicing), and c.7276G>T, p.(Glu2426*). Short stature, early‐onset osteoarthritis, brachydactyly, midfacial hypoplasia, and early growth cessation were the common phenotypic features. The 48 children who received rhGH (and GnRHa) treatment had a significant height improvement compared with before (−2.18 ± 1.06 SD vs. −2.69 ± 0.95 SD, p < 0.001). The heights of children who received rhGH (and GnRHa) treatment were significantly improved compared with those of untreated adults (−2.20 ± 1.10 SD vs. −3.24 ± 1.14 SD, p < 0.001). Conclusion: Our study achieves a new understanding of the phenotypic spectrum, diagnosis, and management of individuals with ACAN variants. No clear genotype–phenotype relationship of patients with ACAN variants was found. Gene sequencing is necessary to diagnose ACAN variants that cause short stature. In general, appropriate rhGH and/or GnRHa therapy can improve the adult height of affected pediatric patients caused by ACAN variants. [ABSTRACT FROM AUTHOR]

This article explores the role of genetic and epigenetic factors in hepatocarcinogenesis, specifically focusing on the impact of focal adhesions Kindlin-1 and Kindlin-2. The study analyzes the allelic frequencies of certain genes in Chinese populations compared to Caucasian and African populations, finding significant differences. However, there is no significant difference in the distribution frequencies of these genes between healthy subjects and hepatoma patients, suggesting that genetic factors may not be involved in hepatoma occurrence. The study also examines DNA methylation levels and finds that epigenetic modifications of Kindlins may be associated with hepatocarcinogenesis. Further research is needed to investigate the causal relationship between epigenetic modifications and gene expression, as well as the clinical outcomes of hepatoma patients. [Extracted from the article]

Objective: To evaluate whether primary care providers' participation in the Comprehensive Primary Care Plus Initiative (CPC+) was associated with changes in their delivery of high‐value services. Data Sources: Medicare Physician & Other Practitioners public use files from 2013 to 2019, 2017 to 2019 Medicare Part B claims for a 5% random sample of Medicare Fee‐for‐Service (FFS) beneficiaries, the Area Health Resources File, the National Plan & Provider Enumeration System files, and public use datasets from the Centers for Medicare & Medicaid Services Physician Compare. Study Design: We used a difference‐in‐difference approach with a propensity score‐matched comparison group to estimate the association of CPC+ participation with the delivery of annual wellness visits (AWVs), advance care planning (ACP), flu shots, counseling to prevent tobacco use, and depression screening. These services are prominent examples of high‐value services, providing benefits to patients at a reasonable cost. We examined both the likelihood of delivering these services within a year and the count of services delivered per 1000 Medicare FFS beneficiaries per year. Data Collection/Extraction Methods: Secondary data are linked at the provider level. Principal Findings: We find that CPC+ participation was associated with increases in the likelihood of delivering AWVs (13.03 percentage points by CPC+'s third year, p < 0.001) and the number of AWVs per 1000 Medicare FFS beneficiaries (44 more AWVs by CPC+'s third year, p < 0.001). We also find that CPC+ participation was associated with more flu shots per 1000 beneficiaries (52 more shots by CPC+'s third year, p < 0.001) but not with the likelihood of delivering flu shots. We did not find consistent evidence for the association between CPC+ participation and ACP services, counseling to prevent tobacco use, or depression screening. Conclusions: CPC+ participation was associated with increases in the delivery of AWVs and flu shots, but not other high‐value services. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effect of dexmedetomidine (Dex) on inflammation and organ injury in sepsis, as well as the potential relationship between Dex and nuclear receptor 77 (Nur77). Methods: We investigated the effects of dexmedetomidine on lipopolysaccharide (LPS)‐induced inflammation in RAW264.7 cells and organ injury in the cecal ligation and puncture (CLP) mouse model. Additionally, we examined the relationship between dexmedetomidine and Nur77. The expression levels of Nur77 in RAW264.7 cells were analyzed under various types of stimulation using quantitative reverse transcription polymerase chain reaction and western blot analysis. Inflammatory cytokine levels in the cells were evaluated using enzyme‐linked immunoassay. Organ injuries were assessed by examining tissue histology and pathology of the lung, liver, and kidney. Results: Dexmedetomidine increased the expression of Nur77 and IL‐10, and downregulated inflammatory cytokines (IL‐1β and TNF‐α) in LPS‐treated RAW264.7 cells. The effect of dexmedetomidine on inhibiting inflammation in LPS‐treated RAW264.7 cells was promoted by overexpressing Nur77, while it was reversed by downregulating Nur77. Additionally, dexmedetomidine promoted the expression of Nur77 in the lung and CLP‐induced pathological changes in the lung, liver, and kidney. Activation of Nur77 with the agonist Cytosporone B (CsnB) significantly suppressed the production of IL‐1β and TNF‐α in LPS‐treated RAW264.7 cells. In contrast, knockdown of Nur77 augmented IL‐1β and TNF‐α production in LPS‐treated RAW264.7 cells. Conclusion: Dexmedetomidine can attenuate inflammation and organ injury, at least partially, via upregulating Nur77 in sepsis. [ABSTRACT FROM AUTHOR]

Background: In the past decade, the field of tumour immunotherapy has made a great progress. However, the efficacy of immune checkpoint blocking (ICB) in the treatment of hepatocellular carcinoma (HCC) remains limited. Cytotoxic lymphocyte trafficking into tumours is critical for the success of ICB. Therefore, additional strategies that increase cytotoxic lymphocyte trafficking into tumours are urgently needed to improve patient immune responses. Methods: Paired adjacent tissue and cancerous lesions with HBV‐associated HCC were subjected to RNA‐seq analysis. Bone morphogenetic protein (BMP9), which reflects vessel normalisation, was identified through Cytoscape software, clinical specimens and Gene Expression Omnibus (GEO) datasets for HCC. The functional effects and mechanism of BMP9 on the tumour vasculature were evaluated in cells and animals. An ultrasound‐targeted microbubble destruction (UTMD)‐mediated BMP9 delivery strategy was used to normalise the vasculature and evaluate therapeutic efficacy mediated by cytotoxic lymphocytes (NK cells) in combination with a PD‐L1 antibody in human cancer xenografts of immune‐deficient mice. Results: We discovered that hepatitis B virus (HBV) infection‐induced downregulation of BMP9 expression correlated with a poor prognosis and pathological vascular abnormalities in patients with HCC. BMP9 overexpression in HBV‐infected HCC cells promoted intra‐tumoural cytotoxic lymphocyte infiltration via vascular normalisation by inhibiting the Rho‐ROCK‐myosin light chain (MLC) signalling cascade, resulting in enhanced efficacy of immunotherapy. Furthermore, UTMD‐mediated BMP9 delivery restored the anti‐tumour function of cytotoxic lymphocytes (NK cells) and showed therapeutic efficacy in combination with a PD‐L1 antibody in human cancer xenografts of immune‐deficient mice. Conclusions: HBV‐induced BMP9 downregulation causes vascular abnormalities that inhibit intra‐tumoural cytotoxic lymphocyte infiltration, providing a rationale for developing and combining immunotherapy with BMP9‐based therapy to treat HBV‐associated HCC. [ABSTRACT FROM AUTHOR]

Abstract: Surfactant flooding as a potential enhanced oil‐recovery technology in a high‐temperature and high‐salinity oil reservoir after water flooding has attracted extensive attention. In this study, the synthesis of an alkyl alcohol polyoxyethylene ether sulfonate surfactant (C12EO7S) with dodecyl alcohol polyoxyethylene ether and sodium 2‐chloroethanesulfonate monohydrate, and its adaptability in surfactant flooding were investigated. The fundamental parameters of C12EO7S were obtained via surface tension measurement. And the ability to reduce oil–water interfacial tension (IFT), wettability alteration, emulsification, and adsorption was determined. The results illustrated that IFT could be reduced to 10−3 mN m−1 at high temperature and high salinity without additional additives, and C12EO7S exhibited benign wettability alternate ability, and emulsifying ability. Furthermore, the oil‐displacement experiments showed that C12EO7S solution could remarkably enhance oil recovery by 16.19% without adding any additives. [ABSTRACT FROM AUTHOR]

Phosphodiesterase 3B (PDE3B) gene expression is generally reduced in large adipocytes of obese, insulin-resistant mice. This reduced gene expression is restored by peroxisome proliferator-activated receptor (PPAR) γ ligands accompanied by a reduced fat cell size. To determine whether PDE3B gene expression is regulated by PPARγ itself, we analyzed lean PPARγ (+/−) mice with adipocyte size comparable to control PPARγ (+/+) mice. In adipocytes of PPARγ (+/−) mice, PDE3B mRNA and protein were both reduced to 63% of wild-type levels. Basal PDE activity tended to be decreased to 70% of wild-type levels, and, similarly, insulin-induced PDE activity was significantly decreased to 70%. Thus, PPARγ is required for PDE3B gene expression independent of adipocyte size. [Copyright &y& Elsevier]

The recognition of adiposity as a risk factor for gastric cancer is mainly based on traditional anthropometric indices, such as body mass index, which are unable to discriminate between lean and fat mass. We undertook this study to examine body composition and subsequent risk of gastric cancer. This is a prospective analysis of participants free of cancer from the UK Biobank. We measured baseline body composition with electrical bioimpedance analysis and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders. We documented 326 cases of cancer from 474,929 participants over a median follow‐up of 6.6 years. Both male (HR 1.70, 95% CI 1.01 to 2.89) and female participants (HR 2.47, 95% CI 1.15 to 5.32) in the highest quartile of whole body fat‐free mass were associated with increased risk of gastric cancer as compared with those in the lowest quartile.Whole body fat mass was associated with a decreased risk of gastric cancer (HR per 5‐unit increase 0.86, 95% CI 0.74 to 0.99) in females, but not in males. We concluded that fat‐free mass and fat mass may have different effects on gastric cancer risk. This study provided evidence for individualized weight management for the prevention of gastric cancer. [ABSTRACT FROM AUTHOR]

Objectives: Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC. Methods: All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. Results: The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile. Conclusions: The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Objectives: This phase I study aimed to evaluate the antitumor effect and safety of programmed death‐ligand‐1 (PD‐L1)–targeting autologous chimeric antigen receptor T (CAR‐T) cells for patients with non‐small cell lung cancer (NSCLC). Methods: Programmed death‐ligand‐1–specific CAR‐T cells were generated using lentiviral transduction. Four patients with NSCLC were recruited, but only one patient was finally involved. CAR‐T cells were infused on three different days (total dose during therapy, 1 × 106 CAR‐T cells kg−1 body weight). The date on which the patient received the first CAR‐T cell infusion was designated as Day 0. Results: Circulating CAR‐T cells accounted for 3.30% of the patient's peripheral blood T cells detected by FACS analysis during the first follow‐up (Day +29). The chest CT scan showed subtle tumor shrinkage (stable disease). On Day +43, the patient developed pyrexia without any known causes and dyspnoea that rapidly deteriorated to respiratory failure in 3 days. The chest X‐ray and CT scan showed bilateral extensive pulmonary infiltration in addition to the tumor silhouette on the left upper lung. The interleukin (IL)‐6 levels in serum dramatically increased (> 100‐fold). The patient was immediately transferred to the ICU where he received oxygen and intravenous infusions of tocilizumab and methylprednisolone. His symptoms rapidly improved and the pulmonary inflammation gradually resolved. Conclusion: The clinical manifestations and test findings for this patient with NSCLC might represent unique clinical manifestations of solitary organ damage secondary to PD‐L1–specific CAR‐T cell therapy. The differential diagnosis, underlying mechanism and prevention and treatment strategies for such complications have also been discussed. [ABSTRACT FROM AUTHOR]

Influenza poses a severe threat to global health. Despite the whole inactivated virus (WIV)‐based nasal vaccine being a promising strategy for influenza protection, the mucosal barrier is still a bottleneck of the nasal vaccine. Here, a catalytic mucosal adjuvant strategy for an influenza WIV nasal vaccine based on chitosan (CS) functionalized iron oxide nanozyme (IONzyme) is developed. The results reveal that CS‐IONzyme increases antigen adhesion to nasal mucosa by 30‐fold compared to H1N1 WIV alone. Next, CS‐IONzyme facilitates H1N1 WIV to enhance CCL20‐driven submucosal dendritic cell (DC) recruitment and transepithelial dendrite(TED) formation for viral uptake via the toll‐like receptor(TLR) 2/4‐dependent pathway. Moreover, IONzyme with enhanced peroxidase (POD)‐like activity by CS modification catalyzes a reactive oxygen species (ROS)‐dependent DC maturation, which further enhances the migration of H1N1 WIV‐loaded DCs into the draining lymph nodes for antigen presentation. Finally, CS‐IONzyme‐based nasal vaccine triggers an 8.9‐fold increase of IgA‐mucosal adaptive immunity in mice, which provides a 100% protection against influenza, while only a 30% protection by H1N1 WIV alone. This work provides an antiviral alternative for designing nasal vaccines based on IONzyme to combat influenza infection. [ABSTRACT FROM AUTHOR]

Background: Nonsyndromic hearing loss is clinically and genetically heterogeneous. In this study, we characterized the clinical features of 12 Chinese Han deaf families in which mutations in common deafness genes GJB2, SLC26A4, and MT‐RNR1 were excluded. Methods: Targeted next‐generation sequencing of 147 known deafness genes was performed in probands of 10 families, while whole‐exome sequencing was applied in those of the rest two. Results: Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands, with 16 mutations being novel. Intrafamilial cosegregation of the mutations and the deafness phenotype were confirmed by Sanger sequencing. Conclusion: Our results expanded the mutation spectrum and genotype‒phenotype correlation of nonsyndromic hearing loss in Chinese Hans and also emphasized the importance of combining both next‐generation sequencing and detailed auditory evaluation to achieve a more accurate diagnosis for nonsyndromic hearing loss. [ABSTRACT FROM AUTHOR]

Objectives: Fluoropyrimidine‐based chemotherapy regimens are the current first‐line treatment for metastatic colorectal cancer (mCRC); however, the outcome is often unsatisfactory. The present study aimed to determine the effect of combined cytokine‐induced killer (CIK) cell immunotherapy and first‐line chemotherapy in patients with mCRC. Methods: This retrospective study included 252 patients with mCRC treated with first‐line chemotherapy. Among them, 126 patients received first‐line chemotherapy only (control group), while the other 126 patients, with similar demographic and clinical characteristics, received CIK cell immunotherapy combined with first‐line chemotherapy (CIK group). Overall survival (OS) and progression‐free survival (PFS) were compared between the two groups using the Kaplan–Meier method. Results: The median OS for the CIK group was 54.7 versus 24.1 months for the controls, and the median PFS for the CIK group was 25.7 versus 14.6 months for the controls. Univariate and multivariate analyses indicated that CIK cell treatment was an independent prognostic factor for patients' OS and PFS. Subgroup analyses showed that CIK cell treatment significantly improved the OS and PFS of patients with metastatic colon cancer, but not those with metastatic rectal cancer. Additionally, the change in CD3+CD56+ subsets after the fourth treatment cycle might be an indicator of successful CIK cell treatment: Patients with increased CD3+CD56+ subsets had better survival than those with decreased CD3+CD56+ subsets. Conclusion: Cytokine‐induced killer cell immunotherapy combined with first‐line chemotherapy could significantly improve the OS and PFS of patients with mCRC, particularly for patients with metastatic colon cancer. [ABSTRACT FROM AUTHOR]

Abstract: A honeycomb‐like 3D N/S co‐doped porous carbon‐coated cobalt sulfide (CoS, Co9S8, and Co1–xS) composite (CS@PC) is successfully prepared using polyacrylonitrile (PAN) as the nitrogen‐containing carbon source through a facile solvothermal method and subsequent in situ conversion. As an anode for lithium‐ion batteries (LIBs), the CS@PC composite exhibits excellent electrochemical performance, including high reversible capacity, good rate capability, and cyclic stability. The composite electrode delivers specific capacities of 781.2 and 466.0 mAh g−1 at 0.1 and 5 A g−1, respectively. When cycled at a current density of 1 A g−1, it displays a high reversible capacity of 717.0 mAh g−1 after 500 cycles. The ability to provide this level of performance is attributed to the unique 3D multi‐level porous architecture with large electrode–electrolyte contact area, bicontinuous electron/ion transport pathways, and attractive structure stability. Such micro‐/nanoscale design and engineering strategies may also be used to explore other nanocomposites to boost their energy storage performance. [ABSTRACT FROM AUTHOR]

ASPP2 is an important tumor suppressor protein promoting p53-dependent and-independent apoptosis. However, it has been unclear how ASPP2 protein is regulated. Here, we identified Itch as the E3 ubiquitin ligase for ASPP2. Itch interacts with ASPP2 and mediates its degradation and ubiquitination in vivo. The PPXY motif of ASPP2 interacts with the WW domains of Itch. Yap1 competes with Itch for binding to ASPP2, and prevents Itch-mediated degradation and ubiquitination of ASPP2. Together, these observations reveal that Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability through competing post-translational regulatory mechanism of ASPP2. [ABSTRACT FROM AUTHOR]

Highlights: [•] A second peak of H2AX phosphorylation appears when G2/M arrest is induced by ionizing radiation. [•] An increased level of γH2AX occurred in mitotic cells in the absence of DNA damage. [•] The mitotic γH2AX can be attenuated by DNA-PKcs inactivation, but not by ATM inhibition. [•] DNA-PKcs/CHK2 pathway mediates the mitotic phosphorylation of H2AX. [ABSTRACT FROM AUTHOR]

Background and Purpose: One key mechanism for endothelial dysfunction is endothelial NOS (eNOS) uncoupling, whereby eNOS generates superoxide (O(2) (•-) ) rather than NO. We explored the effect of pyridoxine on eNOS uncoupling induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism.Experimental Approach: HUVECs were incubated with ox-LDL with/without pyridoxine, N(G) -nitro-L-arginine methylester (L-NAME), chelerythrine chloride (CHCI) or apocynin. Endothelial O(2) (•-) was measured using lucigenin chemiluminescence, and O(2) (•-) -sensitive fluorescent dye dihydroethidium (DHE). NO levels were measured by chemiluminescence, PepTag Assay for non-radioactive detection of PKC activity, depletion of PKCα and p47phox by siRNA silencing and the states of phospho-eNOS Thr495, total-eNOS, phospho-PKCα/βII, total PKC, phospho-PKCα, total PKCα and p47phox were measured by Western blot.Key Results: Ox-LDL significantly increased O(2) (•-) production and reduced NO levels released from HUVECs; an effect reversed by eNOS inhibitor, L-NAME. Pyridoxine pretreatment significantly inhibited ox-LDL-induced O(2) (•-) generation and preserved NO levels. Pyridoxine also prevented the ox-LDL-induced reduction in phospho-eNOS Thr495 and PKC activity. These protective effects of pyridoxine were abolished by the PKC inhibitor, CHCI, or siRNA silencing of PKCα. However, depletion of p47phox or treatment with the NADPH oxidase inhibitor, apocynin, had no influence on these effects. Also, cytosol p47phox expression was unchanged by the different treatments.Conclusions and Implications: Pyridoxine mitigated eNOS uncoupling induced by ox-LDL. This protectant effect was related to phosphorylation of eNOS Thr495 stimulated by PKCα, not via NADPH oxidase. These results provide support for the use of pyridoxine in ox-LDL-related vascular endothelial dysfunction. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE One key mechanism for endothelial dysfunction is endothelial NOS (eNOS) uncoupling, whereby eNOS generates superoxide (O2•−) rather than NO. We explored the effect of pyridoxine on eNOS uncoupling induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism. EXPERIMENTAL APPROACH HUVECs were incubated with ox-LDL with/without pyridoxine, NG-nitro-L-arginine methylester (L-NAME), chelerythrine chloride (CHCI) or apocynin. Endothelial O2•− was measured using lucigenin chemiluminescence, and O2•−-sensitive fluorescent dye dihydroethidium (DHE). NO levels were measured by chemiluminescence, PepTag Assay for non-radioactive detection of PKC activity, depletion of PKCα and p47phox by siRNA silencing and the states of phospho-eNOS Thr495, total-eNOS, phospho-PKCα/βII, total PKC, phospho-PKCα, total PKCα and p47phox were measured by Western blot. KEY RESULTS Ox-LDL significantly increased O2•− production and reduced NO levels released from HUVECs; an effect reversed by eNOS inhibitor, L-NAME. Pyridoxine pretreatment significantly inhibited ox-LDL-induced O2•− generation and preserved NO levels. Pyridoxine also prevented the ox-LDL-induced reduction in phospho-eNOS Thr495 and PKC activity. These protective effects of pyridoxine were abolished by the PKC inhibitor, CHCI, or siRNA silencing of PKCα. However, depletion of p47phox or treatment with the NADPH oxidase inhibitor, apocynin, had no influence on these effects. Also, cytosol p47phox expression was unchanged by the different treatments. CONCLUSIONS AND IMPLICATIONS Pyridoxine mitigated eNOS uncoupling induced by ox-LDL. This protectant effect was related to phosphorylation of eNOS Thr495 stimulated by PKCα, not via NADPH oxidase. These results provide support for the use of pyridoxine in ox-LDL-related vascular endothelial dysfunction. [ABSTRACT FROM AUTHOR]

The MRI showed encephalopathy and brain atrophy of the left parietal lobe, occipital lobe and temporal lobe and decreased infiltration of the dura mater on T2‐weighted imaging. But encephalopathy and brain atrophy could be improved with neurotrophic drugs and additional intelligence teaching. [ABSTRACT FROM AUTHOR]

More substances leaked from a higher-vigor seed sample than from a lower-vigor sample. This indicates that, in some cases, electric conductivity does not represent seed vigor level very well, especially for high-vigor seeds. Results from germination, germination index, leachate conductivity, and the ratio of K+/Na+ from three-seed lots of Chinese cabbage ( Brassica pekinensis (Louv.) Rupr) showed that K+/Na+ correlated well with germination and germination index. The ability of K+/Na+ to indicate well changes in vigor was further supported by investigation in soybean ( Glycine max (L.) Merr.) seeds and another cultivar of Chinese cabbage seeds. Thus, seed leakage of K+/Na+ can accurately indicate seed vigor, whereas the conductivity test failed to do so. Furthermore, K+/Na+ showed up bigger quantitative differences in vigor level than did the conductivity test. This findings provide a more sensitive and accurate index for the assessment of seed vigor. The mechanisms of Na+ and K+ ion transport are also discussed. (Managing editor: Ping HE) [ABSTRACT FROM AUTHOR]