Celastrol inhibits platelet function and thrombus formation.

INTRODUCTION: Celastrol is an active pentacyclic triterpenoid extracted from Tripterygium wilfordii and has anti-inflammatory and anti-tumor properties. Whether Celastrol modulates platelet function remains unknown. Our study investigated its role in platelet function and thrombosis. METHODS: Human platelets were isolated and incubated with Celastrol (0, 1, 3 and 5 µM) at 37 °C for 1 h to measure platelet aggregation, granules release, spreading, thrombin-induced clot retraction and intracellular calcium mobilization. Additionally, Celastrol (2 mg/kg) was intraperitoneally administrated into mice to evaluate hemostasis and thrombosis in vivo. RESULTS: Celastrol treatment significantly decreased platelet aggregation and secretion of dense or alpha granules induced by collagen-related peptide (CRP) or thrombin in a dose-dependent manner. Additionally, Celastrol-treated platelets showed a dramatically reduced spreading activity and decreased clot retraction. Moreover, Celastrol administration prolonged tail bleeding time and inhibited formation of arterial/venous thrombosis. Furthermore, Celastrol significantly reduced calcium mobilization. CONCLUSION: Celastrol inhibits platelet function and venous/arterial thrombosis, implying that it might be utilized for treating thrombotic diseases.

ALDOB/KAT2A interactions epigenetically modulate TGF-ß expression and T cell functions in hepatocellular carcinogenesis.

BACKGROUND AND AIMS: Cross talk between tumor cells and immune cells enables tumor cells to escape immune surveillance and dictate responses to immunotherapy. Previous studies have identified that downregulation of the glycolytic enzyme fructose-1,6-bisphosphate aldolase B (ALDOB) in tumor cells orchestrated metabolic programming to favor HCC. However, it remains elusive whether and how ALDOB expression in tumor cells affects the tumor microenvironment in HCC. APPROACH AND RESULTS: We found that ALDOB downregulation was negatively correlated with CD8 + T cell infiltration in human HCC tumor tissues but in a state of exhaustion. Similar observations were made in mice with liver-specific ALDOB knockout or in subcutaneous tumor models with ALDOB knockdown. Moreover, ALDOB deficiency in tumor cells upregulates TGF-ß expression, thereby increasing the number of Treg cells and impairing the activity of CD8 + T cells. Consistently, a combination of low ALDOB and high TGF-ß expression exhibited the worst overall survival for patients with HCC. More importantly, the simultaneous blocking of TGF-ß and programmed cell death (PD) 1 with antibodies additively inhibited tumorigenesis induced by ALDOB deficiency in mice. Further mechanistic experiments demonstrated that ALDOB enters the nucleus and interacts with lysine acetyltransferase 2A, leading to inhibition of H3K9 acetylation and thereby suppressing TGFB1 transcription. Consistently, inhibition of lysine acetyltransferase 2A activity by small molecule inhibitors suppressed TGF-ß and HCC. CONCLUSIONS: Our study has revealed a novel mechanism by which a metabolic enzyme in tumor cells epigenetically modulates TGF-ß signaling, thereby enabling cancer cells to evade immune surveillance and affect their response to immunotherapy.

Vascular endothelial cells: a fundamental approach for brain waste clearance.

Accumulation of neurotoxic protein aggregates is the pathological hallmark of neurodegenerative disease. Proper clearance of these waste metabolites is an essential process for maintaining brain microenvironment homeostasis and may delay or even halt the onset and progression of neurodegeneration. Vascular endothelial cells regulate the molecular exchange between the circulation and brain parenchyma, thereby protecting the brain against the entry of xenobiotics and decreasing the accumulation of neurotoxic proteins. In this review, we provide an overview of cerebrovascular endothelial cell characteristics and their impact on waste metabolite clearance. Lastly, we speculate that molecular changes in cerebrovascular endothelial cells are the drivers of neurodegenerative diseases.

Microplastics footprint in nature reserves-a case study on the microplastics in the guano from Yancheng Wetland Rare Birds National Nature Reserve, China.

Bio-ingestion of microplastics poses a global threat to ecosystems, yet studies within nature reserves, crucial habitats for birds, remain scarce despite the well-documented ingestion of microplastics by avian species. Located in Jiangsu Province, China, the Yancheng Wetland Rare Birds Nature Reserve is home to diverse bird species, including many rare ones. This study aimed to assess the abundance and characteristics of microplastics in common bird species within the reserve, investigate microplastic enrichment across different species, and establish links between birds' habitat types and microplastic ingestion. Microplastics were extracted from the feces of 110 birds, with 84 particles identified from 37.27% of samples. Among 8 species studied, the average microplastic abundance ranged from 0.97 ± 0.47 to 43.43 ± 61.98 items per gram of feces, or 1.5 ± 0.87 to 3.4 ± 1.50 items per individual. The Swan goose (Anser cygnoides) exhibited the highest microplastic abundance per gram of feces, while the black-billed gull (Larus saundersi) had the highest abundance per individual. The predominant form of ingested microplastics among birds in the reserve was fibers, with polyethylene being the most common polymer type. Significant variations in plastic exposure were observed among species and between aquatic and terrestrial birds. This study represents the first quantitative assessment of microplastic concentrations in birds within the reserve, filling a crucial gap in research and providing insights for assessing microplastic pollution and guiding bird conservation efforts in aquatic and terrestrial environments.

Factors influencing necrotizing enterocolitis in premature infants in China: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. However, studies with large samples on the factors of NEC in China have not been reported. This meta-analysis aims to systematically review the literature to explore the influencing factors of necrotizing enterocolitis in premature infants in China and provide a reference for the prevention of NEC. METHODS: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang and VIP databases were systematically searched from inception to February 2023. We used Stata14.0 software to perform the systematic review and meta-analysis. We used fixed or random effects models with combined odds ratios (ORs) and 95% confidence intervals (CIs), and quality was evaluated using the Newcastle‒Ottawa Scale (NOS). RESULTS: The total sample was 8616 cases, including 2456 cases in the intervention group and 6160 cases in the control group. It was found that 16 risk factors and 3 protective factors were related to necrotizing enterocolitis in premature infants. Septicemia (OR = 3.91), blood transfusion (OR = 2.41), neonatal asphyxia (OR = 2.46), pneumonia (OR = 6.17), infection (OR = 5.99), congenital heart disease (OR = 4.80), intrahepatic cholestasis of pregnancy (ICP) (OR = 2.71), mechanical ventilation (OR = 1.44), gestational diabetes mellitus (GDM) (OR = 3.08), respiratory distress syndrome (RDS) (OR = 3.28), hypoalbuminemia (OR = 2.80), patent ductus arteriosus (PDA) (OR = 3.10), respiratory failure (OR = 7.51), severe anemia (OR = 2.86), history of antibiotic use (OR = 2.12), and meconium-stained amniotic fluid (MSAF) (OR = 3.14) were risk factors for NEC in preterm infants in China. Breastfeeding (OR = 0.31), oral probiotics (OR = 0.36), and prenatal use of glucocorticoids (OR = 0.38) were protective factors for NEC in preterm infants. CONCLUSIONS: Septicemia, blood transfusion, neonatal asphyxia, pneumonia, infection, congenital heart disease, ICP, GDM, RDS, hypoproteinemia, PDA, respiratory failure, severe anemia, history of antibiotic use and MSAF will increase the risk of NEC in premature infants, whereas breastfeeding, oral probiotics and prenatal use of glucocorticoids reduce the risk. Due to the quantity and quality of the included literature, the above findings need to be further validated by more high-quality studies.

Effects of responsive breastfeeding intervention on breastfeeding and infant growth in China: A randomised controlled trial.

Responsive feeding serves as an important protective factor for infant growth and overall health development. This study based on self-determination theory (SDT) aimed to assess the effects of a responsive breastfeeding (RBF) intervention programme on maternal breastfeeding and infant growth and development. A total of 110 mother-infant pairs were recruited and randomly divided into an intervention group (n = 55) and a control group (n = 55). The primary outcomes were breastfeeding motivation score, breastfeeding self-efficacy (BSE) and exclusive breastfeeding rate; the secondary outcomes were infant physical development at 6 weeks and 3 months. A repeated measures ANOVA indicated that the intervention group had significantly higher Enjoyment scores compared to the control group at three time points: at discharge (MD: 5.28; 95% CI: 3.68 to 6.89; p < 0.001), 6 weeks post-partum (MD: 5.06; 95% CI: 3.80 to 6.31; p < 0.001) and 3 months post-partum (MD: 5.24; 95% CI: 4.12 to 6.35; p < 0.001). Similarly, the intervention group reported significantly higher connection and mother's self-perception scores at discharge (MD: 4.31; 95% CI: 3.07 to 5.56; p < 0.001), 6 weeks post-partum (MD: 4.69; 95% CI: 3.71 to 5.68; p < 0.001) and 3 months post-partum (MD: 4.93; 95% CI: 4.14 to 5.72; p < 0.001), compared to the control group. In contrast, the pressure from significant others scores were higher in the control group relative to the intervention group at discharge (MD: -2.09; 95% CI: -2.88 to -1.31; p < 0.001), 6 weeks post-partum (MD: -4.35; 95% CI: -5.20 to -3.49; p < 0.001) and 3 months (MD: -4.89; 95% CI: -5.70 to -4.08; p < 0.001). Finally, the intervention group also reported higher Instrumental Needs scores at all three time points: at discharge (MD: 1.96; 95% CI: 1.35 to 2.58; p < 0.001), 6 weeks post-partum (MD: 3.58; 95% CI: 3.05 to 4.11; p < 0.001) and 3 months post-partum (MD: 1.18; 95% CI: 0.68 to 1.69; p < 0.001). BSE scores were significantly higher in the intervention group compared to the control group at discharge (MD: 14.29; 95% CI: 10.38 to 18.21; p < 0.001), 6 weeks post-partum (MD: 14.04; 95% CI: 11.05 to 17.02; p < 0.001) and 3 months post-partum (MD: 6.80; 95% CI: 4.66 to 8.94; p < 0.001). The rates of exclusive breastfeeding were higher in the intervention group than in the control group at each stage of the intervention (p < 0.01). At 6 weeks post-partum, the intervention group's infants showed slower weight (t = -0.90, p = 0.371) and length (t = -0.69, p = 0.495) growth compared to the control group, though not significantly. By 3 months post-partum, there was a significant difference in both weight (t = -3.46, p = 0.001) and length (t = -2.95, p = 0.004) between the groups. The findings in this study suggest that the RBF intervention programme based on SDT may be effective in improving mothers' motivation to breastfeed, building breastfeeding self-confidence and increasing the rate of exclusive breastfeeding. The effects of the intervention on infant physical development will need to be verified with longer follow-up in future research.

AI protein structure prediction-based modeling and mutagenesis of a protostome receptor and peptide ligands reveal key residues for their interaction.

The protostome leucokinin (LK) signaling system, including LK peptides and their G protein-coupled receptors, has been characterized in several species. Despite the progress, molecular mechanisms governing LK peptide-receptor interactions remain to be elucidated. Previously, we identified a precursor protein for Aplysia leucokinin-like peptides (ALKs) that contains the greatest number of amidated peptides among LK precursors in all species identified so far. Here, we identified the first ALK receptor from Aplysia, ALKR. We used cell-based IP1 activation assays to demonstrate that two ALK peptides with the most copies, ALK1 and ALK2, activated ALKR with high potencies. Other endogenous ALK-derived peptides bearing the FXXWX-amide motif also activated ALKR to various degrees. Our examination of cross-species activity of ALKs with the Anopheles LK receptor was consistent with a critical role for the FXXWX-amide motif in receptor activity. Furthermore, we showed, through alanine substitution of ALK1, the highly conserved phenylalanine (F), tryptophan (W), and C-terminal amidation were each essential for receptor activation. Finally, we used an artificial intelligence-based protein structure prediction server (Robetta) and Autodock Vina to predict the ligand-bound conformation of ALKR. Our model predicted several interactions (i.e., hydrophobic interactions, hydrogen bonds, and amide-pi stacking) between ALK peptides and ALKR, and several of our substitution and mutagenesis experiments were consistent with the predicted model. In conclusion, our results provide important information defining possible interactions between ALK peptides and their receptors. The workflow utilized here may be useful for studying other ligand-receptor interactions for a neuropeptide signaling system, particularly in protostomes.

General Strategy for Specific Fluorescence Imaging of Homocysteine in Living Cells and In Vivo.

The aberrantly changed level of homocysteine (Hcy) triggers a variety of pathological symptoms and subsequently Hcy-related diseases. Direct and selective visualization of Hcy in biological systems is pivotal to understanding the pathological functions of Hcy at the molecular level. Herein, a general strategy was developed for the specific fluorescence imaging of Hcy through the combination of dual-binding sites and the introduction of a nitro group at the 6-position of the 7-diethylaminocoumarin fluorophore. Also, a series of novel fluorescent probes were exploited for monitoring Hcy with excellent selectivity, high sensitivity, and far-red/near-infrared fluorescence emission. Furthermore, fluorescence imaging of endogenous Hcy dynamics in living cells and in vivo was achieved, providing direct and solid evidence for the increasement of endogenous Hcy in type 2 diabetes mellitus and Alzheimer's disease. This research will greatly advance the development and understanding of the molecular nexus between the Hcy metabolism cascade and the root causes of diseases related to Hcy.

Self-Terminating Surface Reconstruction Induced by High-Index Facets of Delafossite for Accelerating Ammonia Oxidation Reaction Involving Lattice Oxygen.

Ammonia (NH3 ) is a promising hydrogen (H2 ) carrier for future carbon-free energy systems, due to its high hydrogen content and easiness to be liquefied. Inexpensive and efficient catalysts for ammonia electro-oxidation reaction (AOR) are desired in whole ammonia-based energy systems. In this work, ultrasmall delafossite (CuFeO2 ) polyhedrons with exposed high-index facets are prepared by a one-step NH3 -assisted hydrothermal method, serving as AOR pre-catalysts. The high-index CuFeO2 facet is revealed to facilitate surface reconstruction into active Cu-doped FeOOH nanolayers during AOR processes in ammonia alkaline solutions, which is driven by the favorable Cu leaching and terminates as the 2p levels of internal lattice oxygen change. The reconstructed heterostructures of CuFeO2 and Cu-doped FeOOH effectively activate the dehydrogenation steps of NH3 and exhibit a potential improvement of 260 mV for electrocatalytic AOR at 10 mA cm-2 compared to the pre-restructured phase. Further, density functional theory (DFT) calculations confirm that a lower energy barrier of the rate-determining step (*NH3 to *NH2 ) is presented on high-index CuFeO2 facets covered with Cu-doped FeOOH nanolayers. Innovatively, lattice oxygen atoms in Fe-based oxides and oxyhydroxide are involved in the dehydrogenation steps of AOR as a proton acceptor, broadening the horizons for rational designs of AOR catalysts.

Controllable Exfoliation of MOF-Derived Van Der Waals Superstructure into Ultrathin 2D B/N Co-Doped Porous Carbon Nanosheets: A Superior Catalyst for Ambient Ammonia Electrosynthesis.

The electrocatalytic nitrogen reduction reaction (NRR) to synthesize NH3 under ambient conditions is a promising alternative route to the conventional Haber-Bosch process, but it is still a great challenge to develop electrocatalysts' high Faraday efficiency and ammonia yield. Herein, a facile and efficient exfoliation strategy to synthesize ultrathin 2D boron and nitrogen co-doped porous carbon nanosheets (B/NC NS) via a metal-organic framework (MOF)-derived van der Waals superstructure, is reported. The results of experiments and theoretical calculations show that the doping of boron and nitrogen can modulate the electronic structure of the adjacent carbon atoms; which thus, promotes the competitive adsorption of nitrogen and reduces the energy required for ammonia synthesis. The B/NC NS exhibits excellent catalytic performance and stability in electrocatalytic NRR, with a yield rate of 153.4 µg·h-1 ·mg-1 cat and a Faraday efficiency of 33.1%, which is better than most of the reported NRR electrocatalysts. The ammonia yield of B/NC NS can maintain 92.7% of the initial NRR activity after 48 h stability test. The authors' controllable exfoliation strategy using MOF-derived van der Waals superstructure can provide a new insight for the synthesis of other 2D materials.

Cortical vein involvement and its influence in a cohort of adolescents with cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Cortical vein thrombosis (CVT) is a rare form of cerebral venous sinus thrombosis (CVST) in adolescent patients that has received little attention. We aimed to analyze the clinical and radiological features of adolescents with CVST and investigate the effects of CVT involvement. METHODS: Patients aged ≥ 10 to ≤ 18 years and diagnosed with CVST were identified at Xuanwu Hospital, Capital Medical University between January 2015 and August 2022 and divided into two groups according to the presence or absence of cortical vein involvement. Additionally, the patients were also categorized based on their sex. Clinical features, radiological characteristics, and 12-month follow-up outcomes were compared between the two groups. RESULTS: Fifty-three adolescents, including 21 with CVT, were included (mean age: 15.2 ± 1.8 years; females, 54.7%). The CVT group was more likely to experience seizures (P = 0.028) and deterioration (28.6% vs. 6.2%, P = 0.047) during hospitalization than the non-CVT group. Poor short-term outcomes, based on the modified Rankin Scale (mRS) score at discharge, were more common in adolescents with CVT (P = 0.007). The proportions of patients showing edema (42.9% vs. 6.2%, P = 0.004) and mass effect (P = 0.015) were significantly higher in the CVT group. Recanalization was observed in 61.9% and 82.1% of the patients in the CVT and non-CVT groups, respectively, during the first imaging review (median, 22 days). After a 12-month follow-up, female adolescents had more frequent resident secondary headaches than male adolescents (52.9% vs. 12.5%; P = 0.014). CONCLUSIONS: Cortical vein involvement in adolescents with CVST was associated with a higher risk of epilepsy at presentation, deterioration during hospitalization, edema, and mass effect on acute imaging. Moreover, cortical vein involvement may lead to worse short-term outcomes. Sex differences require consideration in etiological analyses and prolonged follow-ups.

Metal-Organic Framework Derived Ni2P/FeP@NPC Heterojunction as Stability Bifunctional Electrocatalysts for Large Current Density Water Splitting.

The construction of heterojunction has been widely accepted as a prospective strategy for the exploration of non-precious metal-based catalysts that possess high-performance to achieve electrochemical water splitting. Herein, we design and prepare a metal-organic framework derived N, P-doped-carbon-encapsulated Ni2P/FeP nanorod with heterojunction (Ni2P/FeP@NPC) for accelerating the water splitting and working stably at industrially relevant high current densities. Electrochemical results confirmed that Ni2P/FeP@NPC could both accelerate the hydrogen and oxygen evolution reactions. It could substantially expedite the overall water splitting (1.94 V for 100 mA cm-2) which is close to the performance of RuO2 and the Pt/C couple (1.92 V for 100 mA cm-2). In particular, the durability test exhibited that Ni2P/FeP@NPC delivers 500 mA cm-2 without decay after 200 h, demonstrating the great potential for large-scale applications. Furthermore, the density functional theory simulations demonstrated that the heterojunction interface could give rise to the redistribution of electrons, which could not only optimize the adsorption energy of H-containing intermediates to achieve the optimal ΔGH* in a hydrogen evolution reaction, but also reduce the ΔG value in the rate-determining step of an oxygen evolution reaction, thus improving the HER/OER performance.

Recent Advances in N-O Bond Cleavage of Oximes and Hydroxylamines to Construct N-Heterocycle.

Oximes and hydroxylamines are a very important class of skeletons that not only widely exist in natural products and drug molecules, but also a class of synthon, which have been widely used in industrial production. Due to weak N-O σ bonds of oximes and hydroxylamines, they can be easily transformed into other functional groups by N-O bond cleavage. Therefore, the synthesis of N-heterocycle by using oximes and hydroxylamines as nitrogen sources has attracted wide attention. Recent advances for the synthesis of N-heterocycle through transition-metal-catalyzed and radical-mediated cyclization classified by the type of nitrogen sources and rings are summarized. In this paper, the recent advances in the N-O bond cleavage of oximes and hydroxylamines are reviewed. We hope that this review provides a new perspective on this field, and also provides a reference to develop environmentally friendly and sustainable methods.

Fructose-1,6-Bisphosphate Aldolase B Depletion Promotes Hepatocellular Carcinogenesis Through Activating Insulin Receptor Signaling and Lipogenesis.

BACKGROUND AND AIMS: Insulin receptor (IR) transduces cell surface signal through phosphoinositide 3-kinase (PI3K)-AKT pathways or translocates to the nucleus and binds to the promoters to regulate genes associated with insulin actions, including de novo lipogenesis (DNL). Chronic activation of IR signaling drives malignant transformation, but the underlying mechanisms remain poorly defined. Down-regulation of fructose-1,6-bisphosphate aldolase (ALDO) B in hepatocellular carcinoma (HCC) is correlated with poor prognosis. We aim to study whether and how ALDOB is involved in IR signaling in HCC. APPROACH AND RESULTS: Global or liver-specific ALDOB knockout (L-ALDOB-/- ) mice were used in N-diethylnitrosamine (DEN)-induced HCC models, whereas restoration of ALDOB expression was achieved in L-ALDOB-/- mice by adeno-associated virus (AAV). 13 C6 -glucose was employed in metabolic flux analysis to track the de novo fatty acid synthesis from glucose, and nontargeted lipidomics and targeted fatty acid analysis using mass spectrometry were performed. We found that ALDOB physically interacts with IR and attenuates IR signaling through down-regulating PI3K-AKT pathways and suppressing IR nuclear translocation. ALDOB depletion or disruption of IR/ALDOB interaction in ALDOB mutants promotes DNL and tumorigenesis, which is significantly attenuated with ALDOB restoration in L-ALDOB-/- mice. Notably, attenuated IR/ALDOB interaction in ALDOB-R46A mutant exhibits more significant tumorigenesis than releasing ALDOB/AKT interaction in ALDOB-R43A, whereas knockdown IR sufficiently diminishes tumor-promoting effects in both mutants. Furthermore, inhibiting phosphorylated AKT or fatty acid synthase significantly attenuates HCC in L-ALDOB-/- mice. Consistently, ALDOB down-regulation is correlated with up-regulation of IR signaling and DNL in human HCC tumor tissues. CONCLUSIONS: Our study reports a mechanism by which loss of ALDOB activates IR signaling primarily through releasing IR/ALDOB interaction to promote DNL and HCC, highlighting a potential therapeutic strategy in HCC.

Resistance analysis of grape Botrytis cinerea based on PCR and sequencing technology.

Resistance of grape Botrytis cinerea was analyzed based on PCR and sequencing technology, which provided a reasonable basis for guiding the species and usage of grape Botrytis cinerea. 104 monospora strains of grape B. cinerea were collected from the main grape-producing areas of China. After isolation and purification, the grape B. cinerea DNA was extracted, and PCR primers were designed according to the resistance mechanism of pyrimethene to pyrimethamines, pyridamines and diformolines. Sequence analysis showed that the resistance frequency of B. cinerea to pyrimidine was 22.22%-62.5%, the high-resistant strain frequency was 44.23%, and the mid-temperature zone was 62.5%. The total resistance rate of B. cinerea to pyrimidine was 42.60%. The resistance rate of B. cinerea to pyrimidine was 42.60%. Resistance frequencies of grape gray mold strains were significantly different. The resistance frequencies of grape gray mold strains to pyridimide were significant. The highest resistance frequencies of grape gray mold strains were 53.42% in the cool temperature zone. Only 3.85% of grape gray mold strains showed resistance to pyridimide. Therefore, the resistance of Grape B. cinerea to pyrimidine and pyrimidine is relatively common, and the resistance to enoylmorpholine is still in the initial stage.

Direct Quantification and Visualization of Homocysteine, Cysteine, and Glutathione in Alzheimer's and Parkinson's Disease Model Tissues.

Alzheimer's disease (AD) and Parkinson's disease (PD) are chronic neurodegenerative diseases with high morbidity and mortality. Homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) are closely related to AD and PD. However, the dynamics of Hcy, Cys, and GSH in the brain tissues and the potential pathogenesis between Cys/Hcy/GSH with AD and PD remain unclear. Herein, a novel fluorescent probe 1 with multiple binding sites was rationally designed and exploited for the direct quantification of serum total Hcy and Cys along with superior optical properties. Importantly, differentiation and simultaneity fluorescence imaging of Cys, Hcy, and GSH dynamics were achieved in living cells, tissues, and mouse models of AD and PD with this probe, providing direct evidences for the relationship between Hcy/Cys/GSH and AD/PD for the first time. In addition, pathogenesis studies demonstrated that elevated Hcy and Cys levels are closely related to imbalanced redox homeostasis, increased amyloid aggregates, and nerve cell cytotoxicity. These findings will greatly promote the understanding of the functions of Hcy/Cys/GSH in Alzheimer's and Parkinson's diseases, demonstrating clinical promise for the early diagnosis and prevention of AD and PD.

Prevalence of anxiety and its associated factors among infertile patients after 'two-child' policy in Chongqing, China: a cross-sectional study.

BACKGROUND: With the prevalence of infertility increasing every year around the world, it has seriously impacted the individual quality of family and social life. Anxiety is one of the most prevalent anxiety disorders among infertile patients. After the two-child policy, whether it affected the prevalence of anxiety is controversial. This study aimed to determine the prevalence of anxiety and its potential risk factors among Chinese infertile women after the enforcement of 'two-child policy'. METHODS: This cross-sectional study included 693 infertile patients in a reproductive medical center in Chongqing, China, between February 2016 and December 2018. Data was collected by Self-filling questionnaires including basic demographic information and the Generalized Anxiety Disorder-7 (GAD-7). SPSS statistical software (IBM SPSS version 25) was used to analyse the obtained data. Descriptive analysis was used to describe basic information and anxiety scores, the chi-square test and binary logistic regression were used to analyse the relationship between anxiety and other variables. RESULTS: The prevalence of anxiety among total infertile patients was 21.8%, and its 23.5% among first-child infertile patients (FI), and 18.4% among second-child infertile patients (SI) respectively (P > 0.05). Binary logistic regression showed that patients with lower education levels were more likely to have anxiety (P < 0.01). Patients with middle salary incomes were more likely to have anxiety (OR = 1.860, 95% CI: 1.068-3.238). Oral contraception taking history (OR = 1.778, 95% CI: 1.186-2.667), and history of allergy (OR = 2.098, 95% CI: 1.219-3.612) were associated with anxiety. CONCLUSIONS: Under the full liberalization of the "two-child policy", the total prevalence of anxiety among Chinese infertile female is comparatively high. Low education levels, middle incomes, oral contraception taking and allergy history can be the related risk factors of anxiety. We promote that all infertile patients should be evaluated for the prevalence of anxiety, especially those with potential risks, and receive consultant or targeted treatment when needed.

Increased Interleukin-11 Levels Are Correlated with Cardiac Events in Patients with Chronic Heart Failure.

BACKGROUND: Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF. METHODS: The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events. RESULTS: Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations. CONCLUSIONS: Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.

Epigenetic dysregulation of ZEB1 is involved in LMO2-promoted T-cell acute lymphoblastic leukaemia leukaemogenesis.

T-cell acute lymphoblastic leukaemia (T-ALL) is a hematological malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. ZEB1, a member of zinc finger-homeodomain family transcription factor, exhibits crucial function in promoting T-cell differentiation and potentially acts as a tumor suppressor in T-ALL. However, the molecular mechanism by which ZEB1 regulates T-ALL leukaemogenesis remains obscure. Here, we showed that oncogenic LIM only 2 (LMO2) could recruit Sap18 and HDAC1 to assemble an epigenetic regulatory complex, thus inducing histone deacetylation in ZEB1 promoter and chromatin remodeling to achieve transcriptional repression. Furthermore, downregulation of ZEB1 by LMO2 complex results in an increased leukaemia stem cell (LSC) phenotype as well as unsensitivity in response to methotrexate (MTX) chemotherapy in T-ALL cells. Importantly, we demonstrated that Trichostatin A (TSA, a HDAC inhibitor) addition significantly attenuates MTX unsensitivity caused by dysfunction of LMO2/ZEB1 signaling. In conclusion, these findings have identified a molecular mechanism underlying LMO2/ZEB1-mediated leukaemogenesis, paving a way for treating T-ALL with a new strategy of epigenetic inhibitors.

Erratum to "Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice".

[This corrects the article DOI: 10.1155/2017/5635929.].