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Moiré superlattices formed by twisted stacking in van der Waals materials have emerged as a new platform for exploring the physics of strongly correlated materials and other emergent phenomena1-5. However, there remains a lack of research on the mechanical properties of twisted-layer van der Waals materials, owing to a lack of suitable strategies for making three-dimensional bulk materials. Here we report the successful synthesis of a polycrystalline boron nitride bulk ceramic with high room-temperature deformability and strength. This ceramic, synthesized from an onion-like boron nitride nanoprecursor with conventional spark plasma sintering and hot-pressing sintering, consists of interlocked laminated nanoplates in which parallel laminae are stacked with varying twist angles. The compressive strain of this bulk ceramic can reach 14% before fracture, about one order of magnitude higher compared with traditional ceramics (less than 1% in general), whereas the compressive strength is about six times that of ordinary hexagonal boron nitride layered ceramics. The exceptional mechanical properties are due to a combination of the elevated intrinsic deformability of the twisted layering in the nanoplates and the three-dimensional interlocked architecture that restricts deformation from propagating across individual nanoplates. The advent of this twisted-layer boron nitride bulk ceramic opens a gate to the fabrication of highly deformable bulk ceramics.
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Grain boundaries (GBs), with their diversity in both structure and structural transitions, play an essential role in tailoring the properties of polycrystalline materials1-5. As a unique GB subset, {112} incoherent twin boundaries (ITBs) are ubiquitous in nanotwinned, face-centred cubic materials6-9. Although multiple ITB configurations and transitions have been reported7,10, their transition mechanisms and impacts on mechanical properties remain largely unexplored, especially in regard to covalent materials. Here we report atomic observations of six ITB configurations and structural transitions in diamond at room temperature, showing a dislocation-mediated mechanism different from metallic systems11,12. The dominant ITBs are asymmetric and less mobile, contributing strongly to continuous hardening in nanotwinned diamond13. The potential driving forces of ITB activities are discussed. Our findings shed new light on GB behaviour in diamond and covalent materials, pointing to a new strategy for development of high-performance, nanotwinned materials.
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Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3 years (1.8-6.5 years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6 years, body mass index (BMI) < 16 kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.
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Cardiotoxicidade , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Feminino , Masculino , Criança , Pré-Escolar , Estudos Retrospectivos , Lactente , Cardiotoxicidade/etiologia , Cardiotoxicidade/mortalidade , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo/efeitos adversos , Cardiopatias/etiologia , Cardiopatias/mortalidadeRESUMO
Ischemic stroke is a vascular disease that may cause cognitive and behavioral abnormalities. This study aims to assess abnormal brain function in ischemic stroke patients using the percent amplitude of fluctuation (PerAF) method and further explore the feasibility of PerAF as an imaging biomarker for investigating ischemic stroke pathophysiology mechanisms. Sixteen ischemic stroke patients and 22 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (rs-fMRI) scanning, and the resulting data were analyzed using PerAF. Then a correlation analysis was conducted between PerAF values and Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. Finally, the abnormal PerAF values were extracted and defined as features for support vector machine (SVM) analysis. Compared with HCs, ischemic stroke patients showed decreased PerAF in the bilateral cuneus, left middle frontal gyrus, precuneus and right inferior temporal gyrus, and increased PerAF in the bilateral orbital part of middle frontal gyrus and right orbital part of superior frontal gyrus. Correlation analyses revealed that PerAF values in the left orbital part of middle frontal gyrus was negatively correlated with the MoCA scores. The SVM classification of the PerAF values achieved an area under the curve (AUC) of 0.98 and an accuracy of 94.74%. Abnormal brain function has been found among ischemic stroke patients, which may be correlated with visual impairment, attention deficits, and dysregulation of negative emotions following a stroke. Our findings may support the potential of PerAF as a sensitive biomarker for investigating the underlying mechanisms of ischemic stroke.
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OBJECTIVE: To explore the mechanism of Shenrong pills in improving oligoasthenospermia by inhibiting oxidative stress-induced Leydig cell apoptosis in mouse testis. METHODS: The oxidative stress model of mouse Leydig cells (TM3) was induced by 3% hydrogen peroxide (H2O2) of 600 µmol/L, and then TM3 cells were treated with 7.5%, 10% and 12.5% serum containing Shenrong pills, respectively. TM3 cells were divided into normal control group, model group, and low, medium and high dose groups of Shenrong pills containing serum. The cell viability of TM3 after treatment was detected by CCK-8 method, reactive oxygen species (ROS) were detected by DCFH probe method, and SOD-1, CAT, GSH-px, MDA and LPO in cell lysates were detected by ELISA method. The changes of apoptosis-related proteins Bcl-2, Bax in cell lysates were detected by Western Blot. RESULTS: After H2O2 treatment, compared with normal control group, cell viability was significantly decreased (P< 0.01), MDA and LPO contents were significantly increased (P<0.01), SOD-1, CAT and GSH-px contents were significantly decreased (P<0.01). Reactive oxygen species (ROS) were significantly increased, the relative expression ratio of Bcl-2 protein was significantly decreased (P<0.01, P<0.05), and the relative expression of Bax protein was increased. After the administration of Shenrong pills containing serum, the above indexes were reversed to varying degrees. CONCLUSION: Shenrong pills can resist oxidative stress, inhibit the apoptosis of TM3 cells in mice, maintain high levels of testosterone required for spermatogenic cells, and improve the sperm quality of mice with oligonasthenospermia.
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Peróxido de Hidrogênio , Células Intersticiais do Testículo , Camundongos , Animais , Masculino , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Sêmen/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , ApoptoseRESUMO
At present, light transmission, energy saving, environmental protection, and UV-shielding materials are very important for optimizing indoor living environment. Here, a fluorescent transparent wood (FTW) with UV-shielding function was prepared by encapsulating a carbon quantum dot and epoxy resin into a delignification wood template. FTW exhibits excellent optical transmittance (about 91%), water absorption stability (weight gain rate less than 9%), longitudinal tensile strength (139 MPa), and UV-shielding properties. Due to the photoluminescence characteristics of the carbon quantum dot and the natural cellulose skeleton of wood, FTW can show uniform luminescence under ultraviolet lamps. At the same time, it has remarkable UV-shielding performance. This kind of photoluminescent transparent wood with a UV-shielding function also has the potential to be applied to fields such as electromagnetic shielding and harmful gas detection.
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BACKGROUND: The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. AIM: To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. RESULTS: The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. CONCLUSION: Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.
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BACKGROUND: The impact of type 1 diabetes (T1D) on inflammatory bowel disease (IBD) remains unclear. AIM: To analyze the causal relationship between T1D and IBD using Mendelian ran-domization (MR). METHODS: Single nucleotide polymorphisms were sourced from FinnGen for T1D, IBD, ulcerative colitis (UC) and Crohn's disease (CD). Inverse variance-weighted, MR-Egger, and weighted median tests were used to assess exposure-outcome causality. The MR-Egger intercept was used to assess horizontal pleiotropy. Co-chran's Q and leave-one-out method were used to analyze heterogeneity and sensitivity, respectively. RESULTS: Our MR analysis indicated that T1D was associated with a reduced risk of IBD [odds ratio (OR): 0.959; 95% confidence interval (CI): 0.938-0.980; P < 0.001] and UC (OR: 0.960; 95%CI: 0.929-0.992; P = 0.015), with no significant association observed in terms of CD risk (OR: 0.966; 95%CI: 0.913-1.022; P = 0.227). The MR-Egger intercept showed no horizontal pleiotropy (P > 0.05). Cochran's Q and leave-one-out sensitivity analyses showed that the results were not heterogeneous (P > 0.05) and were robust. CONCLUSION: This MR analysis suggests that T1D serves as a potential protective factor against IBD and UC but is independent of CD.
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BACKGROUND: The benefits and risks of Xileisan (XLS) in the treatment of ulcerative colitis (UC) remain unclear. AIM: The present study aimed to evaluate the efficacy and safety of the combination of XLS and mesalazine when treating UC. METHODS: We searched eight databases for clinical trials evaluating the combination of XLS and mesalazine in the treatment of UC, up to January 2024. Meta-analysis and trial sequential analysis (TSA) were performed using Revman 5.3 and TSA 0.9.5.10 beta, respectively. RESULTS: The present study included 13 clinical studies involving 990 patients, of which 501 patients received XLS combined with mesalazine while 489 patients received mesalazine alone. The meta-analysis showed that, in terms of efficacy, the combination of XLS and mesalazine significantly improved the clinical efficacy rate by 22% [risk ratio (RR) = 1.22; 95%CI: 1.15-1.28; P < 0.00001] and mucosal improvement rate by 25% (RR = 1.25; 95%CI: 1.12-1.39; P = 0.0001), while significantly reducing the duration of abdominal pain by 2.25 days [mean difference (MD) = -2.25; 95%CI: -3.35 to -1.14; P < 0.0001], diarrhea by 2.06 days (MD = -2.06; 95%CI: -3.92 to -0.20; P = 0.03), hematochezia by 2.32 days (MD = -2.32; 95%CI: -4.02 to -0.62; P = 0.008), tumor necrosis factor alpha by 16.25 ng/mL (MD = -16.25; 95%CI: -20.48 to -12.01; P < 0.00001), and interleukin-6 by 14.14 ng/mL (MD = -14.14; 95%CI: -24.89 to -3.39; P = 0.01). The TSA indicated conclusiveness in the meta-analysis of the efficacy endpoints. In terms of safety, the meta-analysis revealed that the combination of XLS and mesalazine did not increase the occurrence of total and gastrointestinal adverse events, abdominal distension, and erythema (P > 0.05). The TSA showed non conclusive findings in the meta-analysis of the safety endpoints. Harbord's test showed no publication bias (P = 0.734). CONCLUSION: Treatment with XLS alleviated the clinical symptoms, intestinal mucosal injury, and inflammatory response in patients with UC, while demonstrating good safety.
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Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 ( PLCZ1 ) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1 -mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1- mutated sperm induced PN formation, suggesting that the Ca 2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.