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Abstract Ligand-protected metal nanoclusters provide an ideal platform for investigating photoredox catalysis. The central challenge is balancing their stability and catalytic activity. Here we show a photochemical reduction–oxidation cascade method for synthesizing an Au8Cu6 nanocluster, which features a robust structure and active surface. Photoredox catalytic activity of Au8Cu6 is developed for the functionalization of alkynes under oxidative conditions. Mechanism studies based on the precise structure reveal the catalytic process of the Au8Cu6 nanocluster. Oxidant-dependent selectivity of Au8Cu6 catalysis is developed for chemodivergent synthesis of mono- and di-functionalized products in high efficiency. The results will stimulate more research on metal nanocluster synthesis and catalysis.

Abstract Background N 6-methyladenosine (m6A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m6A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive. Methods Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1flox/flox) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase separation inhibitor 1,6-hexanediol were administered to investigate their roles in diabetic cardiac fibrosis. Histological and biochemical analyses were performed to determine how Alkbh5 and Ythdf2 regulate Notch1 expression in diabetic cardiac fibrosis. NOTCH1 was reconstituted in ALKBH5- and YTHDF2-deficient cardiac fibroblasts and mouse hearts to study its effects on mitochondrial fission and diabetic cardiac fibrosis. Heart tissue samples from patients with diabetic cardiomyopathy were used to validate our findings. Results In mice with diabetic cardiac fibrosis, decreased Notch1 expression was accompanied by high m6A mRNA levels and mitochondrial fission. Fibroblast-specific deletion of Notch1 enhanced mitochondrial fission and cardiac fibroblast proliferation and induced diabetic cardiac fibrosis in mice. Notch1 downregulation was associated with Alkbh5-mediated m6A demethylation in the 3’UTR of Notch1 mRNA and elevated m6A mRNA levels. These elevated m6A levels in Notch1 mRNA markedly enhanced YTHDF2 phase separation, increased the recognition of m6A residues in Notch1 mRNA by YTHDF2, and induced Notch1 degradation. Conversely, epitranscriptomic downregulation rescues Notch1 expression, resulting in the opposite effects. Human heart tissues from patients with diabetic cardiomyopathy were used to validate the findings in mice with diabetic cardiac fibrosis. Conclusions We identified a novel epitranscriptomic mechanism by which m6A-mediated phase separation suppresses Notch1 expression, thereby promoting mitochondrial fission in diabetic cardiac fibrosis. Our findings provide new insights for the development of novel treatment approaches for patients with diabetic cardiac fibrosis.

Abstract Background To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). Methods A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. Results CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p

The pathogenesis of cardiovascular diseases (CVDs) is intricate, with liquid-liquid phase separation (LLPS) considered a crucial regulatory mechanism. Epigenetics is closely intertwined with cardiovascular diseases, involving mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) that play pivotal roles in cardiovascular disease progression and regression. It is known that specific proteins and mRNAs associated with epigenetic modifications exhibit LLPS characteristics, influencing cardiovascular diseases. Consequently, targeting epigenetic modifications to modulate LLPS emerges as a promising strategy for cardiovascular diseases treatment. This review delves into the regulatory impact of liquid-liquid phase separation on cardiovascular diseases, with a specific focus on the epigenetic landscape. The current study sought to investigate the relationship between epigenetic landscape and phase separation in cardiovascular diseases development, as well as their therapeutic implications.

The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.

Abstract Motivated by the recently observed $$D_{s0}(2590)$$ D s 0 ( 2590 ) state by LHCb, we investigate the mass spectrum and the strong decay properties of the charmed-strange mesons within the Godfrey–Isgur model considering the coupled-channel effects. One finds that the $$D^*K^*$$ D ∗ K ∗ contributions to the mass shifts are large for all the charmed-strange states, which is maybe due to the spin-enhancement effect. Our results support that $$D_{s0}^*(2317)$$ D s 0 ∗ ( 2317 ) and $$D_{s1}(2460)$$ D s 1 ( 2460 ) could be interpreted as the $$D_{s}(1^3P_0)$$ D s ( 1 3 P 0 ) and $$D_{s}(1^3P_1)$$ D s ( 1 3 P 1 ) states with larger DK and $$D^*K$$ D ∗ K components, respectively, although the probabilities of the DK and $$D^*K$$ D ∗ K components for $$D_{s0}^*(2317)$$ D s 0 ∗ ( 2317 ) and $$D_{s1}(2460)$$ D s 1 ( 2460 ) are smaller than other theoretical predictions, which may be due to our neglect of the direct interaction of the meson components. Meanwhile, $$D_{s1}(2700)$$ D s 1 ( 2700 ) , $$D_{s1}(2536)$$ D s 1 ( 2536 ) , $$D^*_{s2}(2573)$$ D s 2 ∗ ( 2573 ) , $$D_{s1}^*(2860)$$ D s 1 ∗ ( 2860 ) , $$D_{s3}^*(2860)$$ D s 3 ∗ ( 2860 ) , and $$D_{sJ}^*(3040)$$ D sJ ∗ ( 3040 ) could be well interpreted as the $$D_s(2^3S_1)$$ D s ( 2 3 S 1 ) , $$D_s(1^1P_1)$$ D s ( 1 1 P 1 ) , $$D_s(1^3P_2)$$ D s ( 1 3 P 2 ) , $$D_s(1^3D_1)$$ D s ( 1 3 D 1 ) , $$D_s(1^3D_3)$$ D s ( 1 3 D 3 ) , and $$D_s(2^1P_1)$$ D s ( 2 1 P 1 ) states, respectively. Although the $$D_{s0}(2590)$$ D s 0 ( 2590 ) mass is about 50 MeV less than our prediction for the $$D_{s0}(2S)$$ D s 0 ( 2 S ) state, its width is still in good agreement with the one of $$D_{s0}(2S)$$ D s 0 ( 2 S ) . Therefore, $$D_{s0}(2590)$$ D s 0 ( 2590 ) state needs to be further confirmed by the experimental measurements, and the more precise information about $$D_{s0}(2590)$$ D s 0 ( 2590 ) will shed light on its assignment of $$D_{s0}(2S)$$ D s 0 ( 2 S ) . Furthermore, we predict the masses and the strong decay properties of the charmed-strange mesons with masses around 3 GeV, which would be helpful to experimentally search for these states.

Mulberry crinkle leaf virus (MCLV), identified in mulberry plants (Morus alba L.), is a member of the genus Mulcrilevirus in the family Geminiviridae. The functions of the V2 protein encoded by MCLV remain unclear. Here, Agrobacterium-mediated infectious clones of a wild-type MCLV vII (MCLVWT) and two V2 mutant MCLV vIIs, including MCLVmV2 (with a mutation of the start codon of the V2 ORF) and MCLVdV2 (5′-end partial deletion of the V2 ORF sequence), were constructed to investigate the roles of V2 both in planta and at the cellular level. Although all three constructs (pCA-1.1MCLVWT, pCA-MCLVmV2, and pCA-MCLVdV2) were able to infect both natural host mulberry plants and experimental tomato plants systematically, the replication of the MCLVmV2 and MCLVdV2 genomes in these hosts was significantly reduced compared to that of MCLVWT. Similarly, the accumulation of MCLVmV2 and MCLVdV2 in protoplasts of Nicotiana benthamiana plants was significantly lower than that of MCLVWT either 24 h or 48 h post-transfection. A complementation experiment further confirmed that the decreased accumulation of MCLV in the protoplasts was due to the absence of V2 expression. These results revealed that MCLV-encoded V2 greatly enhances the level of MCLV DNA accumulation and is designated the replication enhancer protein of MCLV.

Objective: Our aim was to develop and validate a nomogram for predicting the in-hospital 14-day (14 d) and 28-day (28 d) survival rates of patients with coronavirus disease 2019 (COVID-19). Methods: Clinical data of patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from December 2022 to February 2023 and the north campus of Shanghai Ninth People's Hospital from April 2022 to June 2022 were collected. A total of 408 patients from Renmin Hospital of Wuhan University were selected as the training cohort, and 151 patients from Shanghai Ninth People's Hospital were selected as the verification cohort. Independent variables were screened using Cox regression analysis, and a nomogram was constructed using R software. The prediction accuracy of the nomogram was evaluated using the receiver operating characteristic (ROC) curve, C-index, and calibration curve. Decision curve analysis was used to evaluate the clinical application value of the model. The nomogram was externally validated using a validation cohort. Result: In total, 559 patients with severe/critical COVID-19 were included in this study, of whom 179 (32.02 %) died. Multivariate Cox regression analysis showed that age >80 years [hazard ratio (HR) = 1.539, 95 % confidence interval (CI): 1.027–2.306, P = 0.037], history of diabetes (HR = 1.741, 95 % CI: 1.253–2.420, P = 0.001), high APACHE II score (HR = 1.083, 95 % CI: 1.042–1.126, P

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms. With the increasing research on cardiac fibrosis, redox has been recognized as an important part of cardiac remodeling, and an imbalance in redox homeostasis can adversely affect the function and structure of the heart. The metabolism of metal ions is essential for life, and abnormal metabolism of metal ions in cells can impair a variety of biochemical processes, especially redox. However, current research on metal ion metabolism is still very limited. This review comprehensively examines the effects of metal ion (iron, copper, calcium, and zinc) metabolism-mediated redox homeostasis on cardiac fibrosis, outlines possible therapeutic interventions, and addresses ongoing challenges in this rapidly evolving field.

Summary: PRMT1 plays a vital role in breast tumorigenesis; however, the underlying molecular mechanisms remain incompletely understood. Herein, we show that PRMT1 plays a critical role in RNA alternative splicing, with a preference for exon inclusion. PRMT1 methylome profiling identifies that PRMT1 methylates the splicing factor SRSF1, which is critical for SRSF1 phosphorylation, SRSF1 binding with RNA, and exon inclusion. In breast tumors, PRMT1 overexpression is associated with increased SRSF1 arginine methylation and aberrant exon inclusion, which are critical for breast cancer cell growth. In addition, we identify a selective PRMT1 inhibitor, iPRMT1, which potently inhibits PRMT1-mediated SRSF1 methylation, exon inclusion, and breast cancer cell growth. Combination treatment with iPRMT1 and inhibitors targeting SRSF1 phosphorylation exhibits an additive effect of suppressing breast cancer cell growth. In conclusion, our study dissects a mechanism underlying PRMT1-mediated RNA alternative splicing. Thus, PRMT1 has great potential as a therapeutic target in breast cancer treatment.

Glutamate plays a crucial role in cognitive impairments after ischemic stroke. There is a scarcity of information about how glutamate-induced activation of cAMP-response element binding (CREB) signaling pathway regulates both the negative and positive regulators of synaptic plasticity. Recent studies have demonstrated the involvement of prominent epigenetic repressors, such as MeCP2 and DNMTs, in stroke. Neuroprotective effects of oxytocin against ischemia have been previously reported, while the underlying mechanism is still elusive. In this research, the possible role of CREB-mediated DNA hypermethylation and the potential mechanism of oxytocin in a rat model of permanent middle cerebral artery occlusion (pMCAO) were assessed. Adult male Sprague-Dawley rats were pretreated with intraperitoneal injection of oxytocin at the onset of pMCAO. The effects of oxytocin on spines and the expression levels of synaptic genes were determined. The regulatory effects of oxytocin on glutamate level, N-methyl-D-aspartate receptors (NMDARs), its downstream CREB pathway, and global or gene-specific DNA methylation status were evaluated by immunofluorescence, co-immunoprecipitation, and chromatin immunoprecipitation, respectively. We found that CREB could act as a common transcription factor for MeCP2 and DNMT3B after ischemic stroke. Oxytocin dose-dependently deactivated NR2B-related CaM-CREB pathway and inhibited DNA hypermethylation at the CpG islands of Ngf gene in pMCAO-operated rats. Moreover, oxytocin prevented pMCAO-induced reduction in the number of spines and neural cells. DNA hypermethylation in Ngf gene contributed to the cognitive deficits post-stroke. The neuroprotective effects of oxytocin against ischemia could be attributed to inhibiting glutamate release, providing additional evidence on the mechanism of oxytocin against ischemic stroke.

Summary: Dysregulated lipid metabolism occurs in pathological processes characterized by cell proliferation and migration. Nonetheless, the mechanism of increased mitochondrial lipid oxidation is poorly appreciated in diabetic cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. Herein, increased WTAP expression promotes cardiac fibroblast proliferation and migration, contributing to diabetic cardiac fibrosis. Knockdown of WTAP suppresses mitochondrial lipid oxidation, fibroblast proliferation and migration to ameliorate diabetic cardiac fibrosis. Mechanistically, WTAP-mediated m6A methylation of AR induced its degradation, dependent on YTHDF2. Additionally, AR directly interacts with mitochondrial lipid oxidation enzyme Decr1; overexpression of AR-suppressed Decr1-mediates mitochondrial lipid oxidation, inhibiting cardiac fibroblast proliferation and migration. Knockdown of AR produced the opposite effect. Clinically, increased WTAP and YTHDF2 levels correlate with decreased AR expression in human DCM heart tissue. We describe a mechanism wherein WTAP boosts higher mitochondrial lipid oxidation, cardiac fibroblast proliferation, and migration by enhancing AR methylation in a YTHDF2-dependent manner.

With the in-depth investigation of cardiac fibrosis, oxidative stress (OS) has been recognized as a significant pathophysiological pathway involved in cardiac remodeling and progression. OS is a condition characterized by the disruption of equilibrium between reactive oxygen species (ROS) produced by the organism and the antioxidant defense system, resulting in adverse effects on the structure and function of the heart. The accumulation of reactive substances beyond cellular thresholds disrupts the normal physiology of both cardiomyocytes and non-cardiomyocytes, leading to OS, inflammation, hypertrophy, and cardiac fibrosis. Furthermore, cardiac OS also modulates several crucial genes involved in maintaining cellular homeostasis, including those associated with mitochondrial biogenesis, injury, and antioxidant defense, which are inevitably associated with concurrent epigenetic changes. Multiple studies have demonstrated the crucial role of epigenetic modifications in regulating cardiac OS. Consequently, modulating OS through targeted epigenetic modifications emerges as a potentially promising therapeutic strategy for managing cardiac fibrosis. This article provides a new review of current research on this subject and proposes that epigenetics may improve OS-induced cardiac fibrosis.

Dysregulated mitochondrial metabolism occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the role of mitochondrial fission is not well appreciated in cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. We investigated the causes and consequences of mitochondrial fission in cardiac fibrosis using cultured cells, animal models, and clinical samples. Increased METTL3 expression caused excessive mitochondrial fission, resulting in the proliferation and migration of cardiac fibroblasts that lead to cardiac fibrosis. Knockdown of METTL3 suppressed mitochondrial fission, inhibiting fibroblast proliferation and migration for ameliorating cardiac fibrosis. Elevated METTL3 and N6-methyladenosine (m6A) levels were associated with low expression of long non-coding RNA GAS5. Mechanistically, METTL3-mediated m6A methylation of GAS5 induced its degradation, dependent of YTHDF2. GAS5 could interact with mitochondrial fission marker Drp1 directly; overexpression of GAS5 suppressed Drp1-mediated mitochondrial fission, inhibiting cardiac fibroblast proliferation and migration. Knockdown of GAS5 produced the opposite effect. Clinically, increased METTL3 and YTHDF2 levels corresponded with decreased GAS5 expression, increased m6A mRNA content and mitochondrial fission, and increased cardiac fibrosis in human heart tissue with atrial fibrillation. We describe a novel mechanism wherein METTL3 boosts mitochondrial fission, cardiac fibroblast proliferation, and fibroblast migration: METTL3 catalyzes m6A methylation of GAS5 methylation in a YTHDF2-dependent manner. Our findings provide insight into the development of preventative measures for cardiac fibrosis.

Summary: Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy. Patient prognosis cannot be accurately assessed in National Comprehensive Cancer Network (NCCN) risk stratification subgroups based on the current criteria. This study aimed to develop a novel prognostic score model for the quantitative prediction of prognosis in AML.ResultsWe developed a prognostic risk scoring model of AML using differentially expressed genes to predict prognosis in patients with AML. Furthermore, we evaluated the effectiveness and clinical significance of this prognostic model in 4 AML cohorts and 905 patients with AML. A prognostic risk scoring model of AML containing eight prognosis-related genes was constructed using a multivariate Cox regression model. The model had a higher predictive value for the prognosis of AML in the training and validation sets. In addition, patients with lower scores had significantly better overall survival (OS) and even-free survival (EFS) than those with higher scores among patients with intermediate-risk AML according to the NCCN guidelines, indicating that the model could be used to further predict the prognosis of the intermediate-risk AML populations. Similarly, patients with high scores had remarkably poor OS and EFS in the normal-karyotype populations, indicating that the scoring model had an excellent predictive performance for patients with AML having normal karyotype.ConclusionsOur study provided an individualized prognostic risk score model that could predict the prognosis of patients with AML.

Coal spontaneous combustion seriously restricts the safe production of coal mines, and adding an inhibitor is one of the effective methods to prevent coal spontaneous combustion. To improve the pertinence and high efficiency of the inhibitor, this paper considered the intrinsic properties and external conditions that affect the occurrence of coal spontaneous combustion, combined with the characteristics that the rare earth hydrotalcite can effectively improve the thermal stability, coupling, and flame retardancy of the coal and the halide inhibitor. The halide inhibitor can enhance the permeability, dispersion, and uniformity of the rare earth hydrotalcite as a carrier. The halide carrier inorganic salt inhibitor was prepared. To study the inhibition mechanism and performance of the halide carrier inorganic salt inhibitor on coal spontaneous combustion, differential scanning calorimetry (DSC) was used to test the variation law of parameters, such as stage characteristics, characteristic temperature, thermal effect, and apparent activation energy in the process of coal spontaneous combustion under the action of a rare earth hydrotalcite, MgCl2 and a halide carrier inorganic salt inhibitor. Test results reveal that the OH of the rare earth hydrotalcite laminate can generate a weak hydrogen bond with acidic functional groups such as −COOH in coal molecules so that the activity of the acidic functional groups is weakened. Mg2+ complexes with −COO− in coal molecules to form −COOMg−, resulting in the weakening of the C=O activity in −COO−, which is the main mechanism of the halide carrier inorganic salts inhibiting coal spontaneous combustion. The endothermic peak of the DSC curve appears as a double peak or multi-peak after the addition of halide carrier inorganic salts to the coal sample. Compared with the raw coal, the peak temperature is shifted back by 50–60 ℃, the T1 temperature is shifted back by 90–100 ℃, and the total heat release decreased by 19–27 kJ·g−1. Furthermore, the apparent activation energy of each stage of the coal body is effectively improved. Results revealed that the halide carrier inorganic salt inhibitor could effectively inhibit the reaction process of coal spontaneous combustion.

BackgroundNon-suicidal self-injury (NSSI) has attracted more and more attention from schools, mental health workers and even the whole society in China. The aim of this study was to explore influencing factors and clinical characteristics of NSSI in adolescent psychiatric patients in China, and provide valuable information for the intervention and treatment of NSSI.MethodsThe sample included 157 adolescents, 114 were female (72.6%), aged 12–18 years (M = 15.39, SD = 1.81). Assessments were performed using Childhood Trauma Questionnaire-Short Form, the Revised Olweus Bully/Victim Questionnaire, the modified version of Adolescents Self-Harm Scale, Montgomery–Asberg Depression Rating Scale, Brief Psychiatric Rating Scale, the Young Mania Rating Scale and the Mini International Neuropsychiatric Interview. Clinical characteristics were collected from electronic medical record system.ResultsAdolescent patients with NSSI experienced more adverse life events including peer bullying, childhood trauma and romantic relationship trouble. They had more times of hospitalization, higher dosage of psychotic medication, and more severe depressive symptoms.ConclusionsIt is very necessary to evaluate negative life events, including childhood trauma, peer bullying etc., in adolescent patients with NSSI. It has important clinical implications for evaluating the risk factors of NSSI and giving effective intervention treatment. Timely and effective treatment of these patients' depressive symptoms will also contribute to the relief of NSSI.

Arginine methyltransferases (PRMTs) are involved in the regulation of various physiological and pathological conditions. Using proteomics, the authors here profile the methylation substrates of PRMTs 4, 5 and 7 and characterize the roles of these enzymes in cancer-associated splicing regulation.

In this study, β-Bi2O3 nanosheets functionalized with bisphenol A (BPA) synthetic receptors were developed by a simple molecular imprinting technology and applied as the photoelectric active material for the construction of a BPA photoelectrochemical (PEC) sensor. BPA was anchored on the surface of β-Bi2O3 nanosheets via the self-polymerization of dopamine monomer in the presence of a BPA template. After the elution of BPA, the BPA molecular imprinted polymer (BPA synthetic receptors)-functionalized β-Bi2O3 nanosheets (MIP/β-Bi2O3) were obtained. Scanning electron microscopy (SEM) of MIP/β-Bi2O3 revealed that the surface of β-Bi2O3 nanosheets was covered with spherical particles, indicating the successful polymerization of the BPA imprinted layer. Under the best experimental conditions, the PEC sensor response was linearly proportional to the logarithm of BPA concentration in the range of 1.0 nM to 1.0 μM, and the detection limit was 0.179 nM. The method had high stability and good repeatability, and could be applied to the determination of BPA in standard water samples.

This study aimed to investigate the role and mechanisms of Receptor interacting protein kinase 2 (RIP2) in pressure overload-induced cardiac remodeling. Human failing or healthy donor hearts were collected for detecting RIP2 expression. RIP2 cardiomyocyte-specific overexpression, RIP2 global knockout, or wild-type mice were subjected to sham or aortic banding (AB) surgery to establish pressure overload-induced cardiac remodeling in vivo. Phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) were used for further investigation in vitro. The expression of RIP2 was significantly upregulated in failing human heart, mouse remodeling heart, and Ang II-treated NRCMs. RIP2 overexpression obviously aggravated pressure overload-induced cardiac remodeling. Mechanistically, RIP2 overexpression significantly increased the phosphorylation of TAK1, P38, and JNK1/2 and enhanced IκBα/p65 signaling pathway. Inhibiting TAK1 activity by specific inhibitor completely prevented cardiac remodeling induced by RIP2 overexpression. This study further confirmed that RIP2 overexpression in NRCM could exacerbate PE-induced NRCM hypertrophy and TAK1 silence by specific siRNA could completely rescue RIP2 overexpression-mediated cardiomyocyte hypertrophy. Moreover, this study showed that RIP2 could bind to TAK1 in HEK293 cells, and PE could promote their interaction in NRCM. Surprisingly, we found that RIP2 overexpression caused spontaneous cardiac remodeling at the age of 12 and 18 months, which confirmed the powerful deterioration of RIP2 overexpression. Finally, we indicated that RIP2 global knockout attenuated pressure overload-induced cardiac remodeling via reducing TAK1/JNK1/2/P38 and IκBα/p65 signaling pathways. Taken together, RIP2-mediated activation of TAK1/P38/JNK1/2 and IκBα/p65 signaling pathways played a pivotal role in pressure overload-induced cardiac remodeling and spontaneous cardiac remodeling induced by RIP2 overexpression, and RIP2 inhibition might be a potential strategy for preventing cardiac remodeling.

Objective: A nomograph model of mortality risk for patients with coronavirus disease 2019 (COVID-19) was established and validated. Methods: We collected the clinical medical records of patients with severe/critical COVID-19 admitted to the eastern campus of Renmin Hospital of Wuhan University from January 2020 to May 2020 and to the north campus of Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, from April 2022 to June 2022. We assigned 254 patients to the former group, which served as the training set, and 113 patients were assigned to the latter group, which served as the validation set. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression were used to select the variables and build the mortality risk prediction model. Results: The nomogram model was constructed with four risk factors for patient mortality following severe/critical COVID-19 (≥3 basic diseases, APACHE II score, urea nitrogen (Urea), and lactic acid (Lac)) and two protective factors (percentage of lymphocyte (L%) and neutrophil-to-platelets ratio (NPR)). The area under the curve (AUC) of the training set was 0.880 (95% confidence interval (95%CI), 0.837~0.923) and the AUC of the validation set was 0.814 (95%CI, 0.705~0.923). The decision curve analysis (DCA) showed that the nomogram model had high clinical value. Conclusion: The nomogram model for predicting the death risk of patients with severe/critical COVID-19 showed good prediction performance, and may be helpful in making appropriate clinical decisions for high-risk patients.

Background and aims: It has been demonstrated that 1,25-hydroxyvitamin-D3-24-hydroxylase, encoded by CYP24A1 gene, is a key enzyme that neutralizes the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in response to hepatitis C virus (HCV) infection. This study aimed to investigate whether CYP24A1 genetic variation is associated with HCV infection outcomes. Methods: 848 HCV chronically infected subjects, 507 natural clearance subjects, and 1017 uninfected controls were enrolled. Nine single nucleotide polymorphisms (SNPs) in theCYP24A1 gene were genotyped using the Sequenom MassARRAY platform. Results: After adjusting for age, gender, and routes of infection, logistic regression analyses showed that rs6013897-A was associated with an elevated risk of HCV infection (P

A new type of hydroxyalkyl starch, γ-hydroxypropyl starch (γ-HPS), was prepared by etherification of alkali-activated starch with 3-chloropropanol. The reaction efficiency, morphological change, thermodynamic and apparent viscosity properties, and other physicochemical characteristics were described. The molar substitution (MS) of modified whole starch was determined to be 0.008, 0.017, 0.053, 0.106, and 0.178, with a ratio of 5%, 15%, 25%, 35%, and 45% 3-chloropropanol to starch (v/w), respectively. Compared to native starch, the granular size and shape and the X-ray diffraction pattern of γ-HPS are not very different. For low-substituted γ-HPS, the implications may be less evident. Thermal stability measurements by means of thermogravimetric analyses and differential scanning calorimetry (TGA-DSC) proved that thermal stability was reduced and water retaining capacity was increased after hydroxypropylation. Furthermore, the findings also showed that the solubility, light transmittance, and retrogradation of γ-HPS pastes could be improved by etherification. The greater the MS of the γ-HPS, the more its freeze–thaw stability and acid resistivity increased. In this study, we provide relevant information for the application of γ-HPS in food and non-food industries.

Plant-mediated interactions between plant viruses and their vectors are important determinants of the population dynamics of both types of organisms in the field. The whitefly Bemisia tabaci can establish mutualism with begomoviruses via their shared host plants. This mutualism is achieved by the interaction between virulence factors and their host proteins. While the virulence factor βC1 encoded by tomato yellow leaf curl China betasatellite (TYLCCNB), a subviral agent associated to the begomovirus tomato yellow leaf curl China virus (TYLCCNV), may interact with plant protein MYC2, thereby establishing the indirect mutualism between TYLCCNV and whitefly, whether other mechanisms are involved remains unknown. Here, we found the in vitro and in vivo interactions between βC1 and tobacco protein S-phase kinase associated protein 1 (NtSKP1). Silencing the expression of NtSKP1 enhanced the survival rate and fecundity of whiteflies on tobacco plants. NtSKP1 could activate the transcription of genes in jasmonic acid (JA) pathways by impairing the stabilization of JAZ1 protein. Moreover, βC1-NtSKP1 interaction could interfere JAZ1 degradation and attenuate the plant JA defense responses. These results revealed a novel mechanism underlying the better performance of whiteflies on TYLCCNV/TYLCCNB-infected plants.

Icariside II (ICA II), a flavonoid derived from Epimediumbrevicormum Maxin in, has multiple biological activities in Chinese traditional medicine. Our study aimed to investigate the potential activity of ICA II against cardiac remodeling and the underlying mechanism. Mice received aorta banding (AB) or sham surgery, and then were randomly divided into ICA II or vehicle (veh) group for 6 weeks. After echocardiography and pressure-volume loop examination, hearts were harvested for histopathological analysis and molecular mechanism investigation. Additionally, neonatal rat cardiomyocytes (NRCM) were used for in vitro experiments. ICA II attenuated the systolic and diastolic cardiac dysfunction, and protected mouse heart from hypertrophy and fibrosis. The underlying mechanism might involve in the regulation of Akt, AMPKα and mTORC. In in vitro experiment, ICA II prevented phenylephrine (PE) induced NRCM hypertrophy by regulating AMPKα/mTORC pathway. This protective effect was disappeared after treatment with Compound C (CpC), an AMPKα inhibitor. Moreover, ICA II activated AMPK at baseline. ICAII was superior to resveratrol in activating AMPKα and similar to AICAR. ICA II protected against cardiac remodeling and NRCM hypertrophy by regulating AMPK/mTORC pathway. ICA II may be a candidate for the treatment of malignant cardiac remodeling. Keywords: Icariside II, Cardiac remodeling, AMPK/mTORC, Cardiomyocyte

Abstract Background The optimal revascularization technique in patients with left main coronary artery disease (CAD) remains controversial. We aimed to compare the long-term performance of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery in treatment of left main CAD. Methods PubMed, EMBASE, and the Cochrane Library were searched until November 16, 2016. Results Six randomized controlled trials and 22 matched observational studies including 22,487 patients and 90,167 patient-years of follow-up were included. PCI was associated with an overall higher risk for the major adverse cardiac and cerebrovascular events (hazard ratio (HR), 1.42; 95% confidence interval (CI), 1.14–1.77), mainly driven by higher rates of myocardial infarction (HR, 1.69; 95% CI, 1.22–2.34) and revascularization (HR, 2.80; 95% CI, 1.86–4.22). The overall risks for all-cause death (HR, 1.05; 95% CI, 0.93–1.20), cardiac death (HR, 1.05; 95% CI, 0.69–1.59), stroke (HR, 0.64; 95% CI, 0.33–1.24), and the composite safety endpoint of death, myocardial infarction, or stroke (HR, 1.06; 95% CI, 0.97–1.16) were similar between PCI and CABG. Stratified analysis based on stent types showed that the increased risk for myocardial infarction associated with PCI was only evident in patients with bare-metal stents or early-generation drug-eluting stents (DES), but not newer-generation DES. Stratified analyses based on study designs showed largely similar findings with the overall analyses, except for a significantly higher incidence of myocardial infarction in adjusted studies (HR, 2.01; 95% CI, 1.64–2.45) but a trend toward higher incidence in randomized trials (HR, 1.39; 95% CI, 0.85–2.27) associated with PCI. Conclusions Compared with CABG, PCI with newer-generation DES might be a safe alternative revascularization strategy for treatment of left main CAD, but is associated with more repeat revascularization.

Spondias pinnata (Linn. f.) Kurz (Anacardiaceae) is widely distributed in tropical Asia, where it is commonly used as a vegetable and fruit, and is attracting increasing research attention. In this study, we investigated the chemical composition and the cytotoxic, antimicrobial, and anti-inflammatory activities of the fruit peel essential oil of S. pinnata (EOSP), which has been consumed as a medicine and condiment in Xishuangbanna, southwest China. A total of 40 components were identified by Gas Chromatography/Mass spectrometry (GC-MS), representing 95.19% of the EOSP, with furfural (17.14%), α-terpineol (13.09%), and ethyl benzoate (9.05%) as the main constituents. EOSP has moderate cytotoxic activity against five cancer cells and obvious antimicrobial activity against five pathogenic strains. In particular, EOSP (Minimal Inhibitory and Fungicidal Concentration, MIC and MFC, 16‒32 µg/mL) showed a 32-times higher inhibition effect against Aspergillus fumigatus than the positive control Tigecycline (MIC and MBC 512‒1024 µg/mL). EOSP also showed strong anti-inflammatory activity by significantly inhibiting nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 cell lines at 0.08‱, with no effect on cell viability. These bioactivities of S. pinnata fruit peel validate its traditional uses and suggest that it could be a new source of natural antimicrobial and anti-inflammatory agents for food or medical industries.

[This corrects the article DOI: 10.1371/journal.pone.0180804.].

BACKGROUND:Many recent trials have investigated the long-term efficacy and safety of endarterectomy versus stenting in treating patients with carotid artery stenosis. We aimed to determine the long-term comparative efficacy and safety of both procedures by pooling this evidence in a meta-analysis. METHODS:We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published until May 6, 2016. Randomized controlled trials, which reported outcomes of interest with a median follow-up of at least 4-year, were included. RESULTS:Eight trials involving 7005 patients and 41824 patient-years of follow-up were included. In terms of the periprocedural outcomes, stenting was associated with a lower risk of myocardial infarction (OR: 0.51; 95% CI: 0.33 to 0.80; P = 0.003) but a higher risk of death or stroke (the composite endpoint, OR: 1.76; 95% CI: 1.38 to 2.25; P < 0.0001), a result that was primarily driven by minor stroke (OR: 2.19; 95% CI: 1.59 to 3.01; P < 0.0001), less so by periprocedural death (OR: 1.68; 95% CI: 0.82 to 3.44; P = 0.16) and major stroke (OR: 1.41; 95% CI: 0.95 to 2.09; P = 0.09). In terms of the long-term outcomes, stenting was associated with a higher risk of stroke (OR 1.45; 95% CI: 1.22 to 1.73; P < 0.0001) and the composite outcome of death or stroke (OR 1.25; 95% CI: 1.05 to 1.48; P = 0.01). No difference was found in long-term all-cause mortality between stenting and endarterectomy (OR: 1.09; 95% CI: 0.95 to 1.26; P = 0.21) and restenosis (OR: 1.48 (95% CI: 0.93 to 2.35; P = 0.10). No evidence of significant heterogeneity was found in any of the analyses. CONCLUSIONS:Carotid endarterectomy was found to be superior to stenting for short- and long-term outcomes, although endarterectomy was associated with a higher risk of periprocedural myocardial infarction. Carotid endarterectomy should be offered as the first choice for carotid stenosis at present, however, more evidence is needed because rapid progress in concurrent devices and medical treatments is being made.

Metamaterials are artificial multifunctional materials that acquire their material properties from their structure, rather than inheriting them directly from the materials they are composed of, and they may provide novel tools to significantly enhance the sensitivity and resolution of sensors. In this paper, we derive the dispersion relation of a cylindrical dielectric waveguide loaded on a negative permeability metamaterial (NPM) layer, and compute the resonant frequencies and electric field distribution of the corresponding Whispering-Gallery-Modes (WGMs). The theoretical resonant frequency and electric field distribution results are in good agreement with the full wave simulation results. We show that the NPM sensor based on a microring resonator possesses higher sensitivity than the traditional microring sensor since with the evanescent wave amplification and the increase of NPM layer thickness, the sensitivity will be greatly increased. This may open a door for designing sensors with specified sensitivity.

Transparent device is deliberately-designed electromagnetic structure that is transparent to electromagnetic wave. It can be used as a radome structure which is capable of protection antenna inside without sacrificing its performance. In this paper, two-dimensional (2D) arbitrary shape electromagnetic transparent device is designed based on transformation optics. Laplace’s equation is adopted to construct the coordinate mapping between the original space and the transformed space. The design method is flexibly extended to three-dimensional (3D) case, which greatly enhances the applicability of transparent device. The protection of a horn antenna is taken as an example to show the effectiveness of the transparent device. Since the performance of the transparent device is independent on the inner antenna, it can be designed separately. Full-wave simulations are made to validate the results.

A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl) and N-hydroxybenzotriazole (HOBt) as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia HL-60 and liver cancer BEL-7402 indicated that (R)-ethyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)-3-(4-hydroxyphenyl) propanoate showed more inhibitory effect against BEL-7402 than 5-FU.

In this paper, we fabricated the ultrathin ZnO p-n homojunctions, which modulated by ZnMgO asymmetrical double barriers (ADB). The ADB p-n homojunctions displays step-like curve in the absorption spectrums, this is the first time that quantum confinement effect has been observed in the absorption spectrums at room temperature (RT). The Hall-effect data confirm there is 2-dimensional electron gas in the interface of the ZnMgO ADB p-n junctions. The quantum confinement effect enhances the hall-mobility μ to 103 cm2V −1s−1 based on the polarity of the films. There was no rectification property in the ZnO homojunctions with thickness of 250nm, however, when the ADB was added in the n-type layer of the homojunctions, it displays a typical Zener diode rectification property in the I-V curve.

We have previously reported that enhanced excitability of dorsal root ganglia (DRG) neurons contributes to the development of bone cancer pain, which severely decreases the quality of life of cancer patients. Nav1.8, a tetrodotoxin-resistant (TTX-R) sodium channel, contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train. We speculate that the Nav1.8 sodium channel is a potential candidate responsible for the enhanced excitability of DRG neurons in rats with bone cancer pain. Here, using electrophysiology, Western blot and behavior assays, we documented that the current density of TTX-R sodium channels, especially the Nav1.8 channel, increased significantly in DRG neurons of rats with cancer-induced bone pain. This increase may be due to an increased expression of Nav1.8 on the membrane of DRG neurons. Accordantly, blockade of Nav1.8 sodium channels by its selective blocker A-803467 significantly alleviated the cancer-induced mechanical allodynia and thermal hyperalgesia in rats. Taken together, these results suggest that functional upregulation of Nav1.8 channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain.

In the title compound, [Cd(C11H7N6)2(H2O)2], the CdII cation is located on an inversion center and is coordinated by four N atoms from two 5-(pyrazin-2-yl)-3-(pyridin-3-yl)-1,2,4-triazolide anions and two water molecules in a distorted octahedral geometry. The triazolide ligand is nearly planar: the central triazole ring is oriented at dihedral angles of 4.63 (13) and 8.41 (13)° with respect to the pyrazine and pyridine rings. Intermolecular O—H...N hydrogen bonds link the molecules into a two-dimensional supramolecular network parallel to (001).

The title compound, C10H13N3S2, is roughly planar (r.m.s. deviation = 0.086 Å). In the crystal, N—H...S hydrogen bonds link the molecules into (001) sheets.

Endocrine therapy has become the fundamental treatment option for hormone receptor-positive (HR+) and receptor tyrosine-protein kinase erbB-2-negative (HER2-) metastatic breast cancer (mBC). While treatments incorporating cyclin-dependent kinase (CDK)4 and 6 inhibitors are more prevalent than ever, comparisons among those regimens are scarce. The aim of the present study was to identify the most effective maintenance treatment for patients with HR+ and HER2- mBC. To this end, databases including PubMed, Embase, Cochrane Library, Scopus and Google Scholar were searched from inception to August, 2023. The endpoints comprised overall survival (OS) and progression free survival (PFS). For dichotomous variants, hazard ratios (HRs) and odds ratios (ORs) were generated, while standard mean difference (SMD) was used for consecutive variants by Bayesian network meta-analysis to make pairwise comparisons among regimens, to determine the optimal therapy. These processes were conducted using Rstudio 4.2.2 orchestrated with STATA 17.0 MP. A total of 16 randomized controlled trials including 7,174 patients with 11 interventions were analyzed. Compared with aromatase inhibitor (AI), palbociclib plus AI (PalboAI) exhibited a significantly longer PFS up to the 36th month of follow-up [HR=1.7; 95% credible interval, 1.36-2.16], including on the 3rd [OR=2.22; 95% confidence interval (CI), 1.10-4.47], 6th (OR=2.39; 95% CI, 1.21-4.69), 12th (OR=1.94; 95% CI, 1.34-2.79), 18th (OR=2.38; 95% CI, 1.65-3.44), 24th (OR=2.39; 95% CI, 1.67-3.43), 30th (OR=2.10; 95% CI, 1.62-2.74) and 36th (OR=2.66; 95% CI, 1.37-5.18) month of follow-up. Additionally, abemaciclib plus fulvestrant exhibited significant effects compared with AI alone between 12 and 36 months. Ribociclib plus fulvestrant, ribociclib plus AI and dalpiciclib plus AI exerted significant effects compared with AI alone between 12 and 30 months. Considering the effect on OS and PFS together with adverse reactions, safety, medical compliance and route of administration, PalboAI was found to be the optimal treatment for HR+/HER2-mBC. However, additional head-to-head clinical trials are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

This is a systematic review of Translator Translation Styles from 2013 to 2023, based on 16 highly relevant articles, which are included after searching a total of 193 articles in three databases using specific keywords. This review aims to investigate the current trend s and development of the four core research elements, namely, the research topics, research approaches/tools, research objects, and research trends of Translator Translation Styles. Corpus -based research and computing technology have become the core research trends in this field. By taking the translated texts as the research objects and using a variety of research approaches to analyze and compile statistics on a large number of texts, researchers can accurately identify and compare the different emphases of their respective studies on Translator Translation Styles. At present, it seems that the research on Translator Translation Styles has established a system framework. However, it still needs to be optimized and improved in some aspects (e.g., the research objects are too limited and lack innovation in types), and future research can further explore those aspect s. The present paper ends with some suggestions and recommendations for future researchers in academic contexts . [ABSTRACT FROM AUTHOR]