Structural and molecular basis for urea recognition by Prochlorococcus.

Nitrogen (N) is an essential element for microbial growth and metabolism. The growth and reproduction of microorganisms in more than 75% of areas of the ocean are limited by N. Prochlorococcus is numerically the most abundant photosynthetic organism on the planet. Urea is an important and efficient N source for Prochlorococcus. However, how Prochlorococcus recognizes and absorbs urea still remains unclear. Prochlorococcus marinus MIT 9313, a typical Cyanobacteria, contains an ABC-type transporter, UrtABCDE, which may account for the transport of urea. Here, we heterologously expressed and purified UrtA, the substrate-binding protein of UrtABCDE, detected its binding affinity toward urea, and further determined the crystal structure of the UrtA/urea complex. Molecular dynamics simulations indicated that UrtA can alternate between "open" and "closed" states for urea binding. Based on structural and biochemical analyses, the molecular mechanism for urea recognition and binding was proposed. When a urea molecule is bound, UrtA undergoes a state change from open to closed surrounding the urea molecule, and the urea molecule is further stabilized by the hydrogen bonds supported by the conserved residues around it. Moreover, bioinformatics analysis showed that ABC-type urea transporters are widespread in bacteria and probably share similar urea recognition and binding mechanisms as UrtA from P. marinus MIT 9313. Our study provides a better understanding of urea absorption and utilization in marine bacteria.

Association between triglyceride glucose-body mass index and long-term adverse outcomes of heart failure patients with coronary heart disease.

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI) is recognized as a reliable surrogate for evaluating insulin resistance and an effective predictor of cardiovascular disease. However, the link between TyG-BMI index and adverse outcomes in heart failure (HF) patients remains unclear. This study examines the correlation of the TyG-BMI index with long-term adverse outcomes in HF patients with coronary heart disease (CHD). METHODS: This single-center, prospective cohort study included 823 HF patients with CHD. The TyG-BMI index was calculated as follows: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. To explore the association between the TyG-BMI index and the occurrences of all-cause mortality and HF rehospitalization, we utilized multivariate Cox regression models and restricted cubic splines with threshold analysis. RESULTS: Over a follow-up period of 9.4 years, 425 patients died, and 484 were rehospitalized due to HF. Threshold analysis revealed a significant reverse "J"-shaped relationship between the TyG-BMI index and all-cause mortality, indicating a decreased risk of all-cause mortality with higher TyG-BMI index values below 240.0 (adjusted model: HR 0.90, 95% CI 0.86-0.93; Log-likelihood ratio p = 0.003). A distinct "U"-shaped nonlinear relationship was observed with HF rehospitalization, with the inflection point at 228.56 (adjusted model: below: HR 0.95, 95% CI 0.91-0.98; above: HR 1.08, 95% CI 1.03-1.13; Log-likelihood ratio p < 0.001). CONCLUSIONS: This study reveals a nonlinear association between the TyG-BMI index and both all-cause mortality and HF rehospitalization in HF patients with CHD, positioning the TyG-BMI index as a significant prognostic marker in this population.

Discovery of a novel hybrid coumarin-hydroxamate conjugate targeting the HDAC1-Sp1-FOSL2 signaling axis for breast cancer therapy.

BACKGROUND: Breast cancer is one of the most lethal cancers in women. Despite significant advances in the diagnosis and treatment of breast cancer, many patients still succumb to this disease, and thus, novel effective treatments are urgently needed. Natural product coumarin has been broadly investigated since it reveals various biological properties in the medicinal field. Accumulating evidence indicates that histone deacetylase inhibitors (HDACIs) are promising novel anti-breast cancer agents. However, most current HDACIs exhibit only moderate effects against solid tumors and are associated with severe side effects. Thus, to develop more effective HDACIs for breast cancer therapy, hydroxamate of HDACIs was linked to coumarin core, and coumarin-hydroxamate hybrids were designed and synthesized. METHODS: A substituted coumarin moiety was incorporated into the classic hydroxamate HDACIs by the pharmacophore fusion strategy. ZN444B was identified by using the HDACI screening kit and cell viability assay. Molecular docking was performed to explore the binding mode of ZN444B with HDAC1. Western blot, immunofluorescent staining, cell viability, colony formation and cell migration and flow cytometry assays were used to analyze the anti-breast cancer effects of ZN444B in vitro. Orthotopic studies in mouse models were applied for preclinical evaluation of efficacy and toxicity in vivo. Proteomic analysis, dual-luciferase reporter assay, chromatin immunoprecipitation, co-immunoprecipitation, immunofluorescent staining assays along with immunohistochemical (IHC) analysis were used to elucidate the molecular basis of the actions of ZN444B. RESULTS: We synthesized and identified a novel coumarin-hydroxamate conjugate, ZN444B which possesses promising anti-breast cancer activity both in vitro and in vivo. A molecular docking model showed that ZN444B binds to HDAC1 with high affinity. Further mechanistic studies revealed that ZN444B specifically decreases FOS-like antigen 2 (FOSL2) mRNA levels by inhibiting the deacetylase activity of HDAC1 on Sp1 at K703 and abrogates the binding ability of Sp1 to the FOSL2 promoter. Furthermore, FOSL2 expression positively correlates with breast cancer progression and metastasis. Silencing FOSL2 expression decreases the sensitivity of breast cancer cells to ZN444B treatment. In addition, ZN444B shows no systemic toxicity in mice. CONCLUSIONS: Our findings highlight the potential of FOSL2 as a new biomarker and therapeutic target for breast cancer and that targeting the HDAC1-Sp1-FOSL2 signaling axis with ZN444B may be a promising therapeutic strategy for breast cancer.

Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal semi-dominant disease, characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-c) from conception and accelerated atherosclerotic cardiovascular disease, often resulting in early death. The aim of this study was to evaluate the prevalence of clinically defined FH in Chinese Han patients with acute coronary syndrome (ACS) and compare the long-term prognosis of ACS patients with and without FH receiving lipid-lowering therapy containing statins after a coronary event. METHODS: All ACS patients were screened at the Second Affiliated Hospital of Xi'an Jiaotong University between Jan 2019 and Sep 2020, and 531 participants were enrolled. All were examined for FH under the Dutch Lipid Clinical Network (DLCN) criteria, and those patients were divided into definite/probable FH, possible FH and unlikely FH. The severity of coronary artery disease was evaluated by the Gensini scoring system. Plasma levels of total cholesterol (TC), triacylglycerol (TG), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), very low-density lipoproteins-cholesterol (VLDL-c), apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and lipoprotein (a) (Lp(a)) were determined centrally at baseline and the last follow-up visit in the fasting state. The non-high-density lipoprotein cholesterol (non-HDL-c) concentration, the TC/HDL-c and apoB/apoA1 ratios were calculated. After FH patients received lipid-lowering treatment containing statin, the target LDL-c levels recommended by the guidelines (LDL-c < 1.8 mmol/L or < 1.4 mmol/L and a reduction > 50% from baseline) were evaluated, and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) during the 12-month follow-up was recorded. RESULTS: The prevalence of clinically definite or probable FH was 4.3%, and the prevalence of possible FH was 10.6%. Compared with the unlikely FH patients with ACS, the FH patients had higher levels of TC, LDL-c, apoB, Lp(a), non-HDL-c, TC/HDL-c and apoB/apoA1 ratio, more severe coronary artery diseases and greater prevalence of left main and triple or multiple vessel lesions. After lipid-lowering therapy containing statins, a minority of FH patients reached the target LDL-c levels defined by the guidelines (χ2 = 33.527, P < 0.001). During the 12-month follow-up, a total of 72 patients experienced MACCE. The survival curve in patients in the FH group was significantly lower than that in the unlikely FH group (HR = 1.530, log-rank test: P < 0.05). Furthermore, the survival curve in patients with high LDL-c (≥ 1.8 mmol/L) was significantly lower than that in patients with low LDL-c (< 1.8 mmol/L) at the 12-month follow-up visit (HR = 1.394, log-rank test: P < 0.05). No significant difference was observed between patients with LDL-c levels ≥ 1.4 mmol/L and with < 1.4 mmol/L at the 12-month follow-up visit by using Kaplan-Meier survival analysis (HR = 1.282, log-rank test: P > 0.05). CONCLUSIONS: FH was an independent risk factor for MACCE in adult patients after a coronary event during long-term follow-up. However, there was inadequate high-intensity statins prescriptions for high-risk patients in this current study. It is important for FH patients to optimize lipid-lowering treatment strategies to reach the target LDL-c level to improve the long-term prognosis of clinical outcomes.

Prevalence of aeroallergen sensitization in children in Northern China.

OBJECTIVE: This study aimed to analyze the sensitization rate of different aeroallergens in children of different age, sex, and disease groups, describe the changing trend of different aeroallergens in different ages, and analyze the sensitization risk factors for asthma. METHODS: Children (<18 years old) with suspected atopic diseases who visited the Department of Allergy of Children's Hospital Affiliated to Capital Institute of Pediatrics and underwent a skin prick test (SPT) were retrospectively enrolled from January 2019 to November 2021. RESULTS: A total of 5465 patients (3514 boys, 1951 girls; mean age, 7 ± 3 years) were enrolled. Of them, 3703 patients (67.8%) were sensitized to at least one aeroallergen. Before 4 years of age, mold was the most prevalent aeroallergen (103/380 [27.1%]), whereas after 4 years of age, weed pollen was the most prevalent aeroallergen. After 6 years of age, tree pollen became the second most prevalent aeroallergen. After 12 years of age, the sensitization rate of indoor aeroallergens was lower than that of outdoor aeroallergens. Logistic regression showed that sensitization to mold (odds ratio [OR]:1.4, 95% confidence interval (CI): 1.2-1.7, p < 0.001), animal dander (OR: 1.6, 95% CI: 1.4-1.9, p < 0.001), and polysensitization (OR: 1.4, 95% CI: 1.0-1.8, p = 0.038) were potential sensitization risk factors for asthma. CONCLUSIONS: Mold is an important allergen in early life. Different kinds of allergens affect different age groups. Patients who are sensitized to mold or animal dander or experience polysensitization should be carefully monitored for asthma risk.

In vivo electrical properties of the healthy liver and the hepatic tumor in a mouse model between 1 Hz and 1 MHz during a thermal treatment.

Objective: Understansding the changing patterns of in vivo electrical properties for the target tissue is crucial for the accurate temperature monitoring and the treatment efficacy in thermal therapy. Our research aims to investigate the changing patterns and the reversibility of in vivo electrical properties for both healthy livers and liver tumors in a mouse model over a frequency range of 1 Hz to 1 MHz at temperatures between 30 °C to 90 °C.Methods and materials: The mice were anesthetized and the target organ was exposed. An 808-nm near-infrared laser was employed as the heating source to heat the organ in vivo. The four-needle electrode, connected to an impedance analyzer, was utilized to obtain the impedance at varying temperatures, which were monitored by a thermocouple.Results: The findings indicated a gradual decline in impedance with an increase in temperature. Furthermore, the impedance was normalized to that at 30 °C, and the real part of the normalized impedance was defined as the k-values, which range from 0 to 1. The results demonstrated a linear correlation between k-values and temperatures (R2 > 0.9 for livers and R2 > 0.8 for tumors). Significant differences were observed between livers and tumors at 1, 10 and 50 kHz (p < 0.05). Additionally, it was demonstrated that the electrical properties could be reversed when the temperature was below or equal to 45 °C.Conclusion: We believe that these results will contribute to the advancement of radiofrequency ablation systems and the development of techniques for temperature monitoring during liver thermal treatment.

Growth differentiation factor-15 predicts all-cause death and major adverse cardiovascular events in patients with coronary heart disease: a prospective cohort study.

The prognostic value of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in coronary heart disease (CHD) patients remains limited. Our study examines the association between GDF-15 and adverse outcomes over an extended period in CHD patients and firstly assesses the incremental prognostic effect of incorporating GDF-15 into the Framingham risk score (FRS)-based model. This single-center prospective cohort study included 3,321 patients with CHD categorized into 2,479 acute coronary syndrome (ACS) (74.6%) and 842 non-ACS (25.4%) groups. The median age was 61.0 years (range: 53.0-70.0), and 917 (27.6%) were females. Mortality and major adverse cardiovascular events (MACEs) included cardiovascular mortality, myocardial infarction (MI), stroke, and heart failure (HF) (inclusive of HF episodes requiring outpatient treatment and/or hospital admission). Cox regression models assessed the associations between GDF-15 and the incidence of all-cause mortality and MACEs. Patients were stratified into three groups based on GDF-15 levels: the first tertile group (< 1,370 ng/L), the second tertile group (1,370-2,556 ng/L), and the third tertile group (> 2,556 ng/L). The C-index, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA) were used to assess incremental value. Over a median 9.4-year follow-up, 759 patients (22.9%) died, and 1,291 (38.9%) experienced MACEs. The multivariate Cox model indicated that GDF-15 was significantly associated with all-cause mortality (per ln unit increase, HR = 1.49, 95% CI: 1.36-1.64) and MACEs (per ln unit increase, HR = 1.29, 95% CI: 1.20-1.38). These associations persisted when GDF-15 was analyzed as an ordinal variable (p for trend < 0.05). Subgroup analysis of ACS and non-ACS for the components of MACEs separately showed a significant association between GDF-15 and both cardiovascular mortality and HF, but no association was observed between GDF-15 and MI /stroke in both ACS and non-ACS patients. The addition of GDF-15 to the FRS-based model enhanced the discrimination for both all-cause mortality (∆ C-index = 0.009, 95% CI: 0.005-0.014; IDI = 0.030, 95% CI: 0.015-0.047; continuous NRI = 0.631, 95% CI: 0.569-0.652) and MACEs (∆ C-index = 0.009, 95% CI: 0.006-0.012; IDI = 0.026, 95% CI: 0.009-0.042; continuous NRI = 0.593, 95% CI: 0.478-0.682). DCA suggested that incorporating GDF-15 into the FRS-based model demonstrated higher net benefits compared to FRS-based models alone (All-cause mortality: FRS-based model: area under the curve of DCA (AUDC) = 0.0903, FRS-based model + GDF-15: AUDC = 0.0908; MACEs: FRS-based model: AUDC = 0.1806, FRS-based model + GDF-15: AUDC = 0.1833). GDF-15 significantly associates with the long-term prognosis of all-cause mortality and MACEs in CHD patients and significantly improves the prognostic accuracy of the FRS-based model for both outcomes.

Establishment of the Prognostic Signature with Genes Related to G2/M Checkpoint in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality in the world. Prognostic indicators such as clinicopathological characteristics and single molecular signature are far from satisfactory in clinical practice. More and more researches have suggested that polygenic prognostic features could predict the prognosis of cancer more precisely than single genes nowadays. In this study, we performed gene set enrichment analysis (GSEA) to identify the sets of TCGA hallmark genes. Univariate Cox regression analysis was used to select preliminary genes, and then multivariate Cox regression analysis was used to identify genes associated with overall survival (OS). We also used Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis to validate the prognostic gene signature. Lastly, qRT-PCR was used to evaluate the expression of these genes in clinical samples, and immunohistochemical staining was performed to confirm the signature. A 12-gene signature was finally built and the risk score was significantly associated with the survival of the patients. Subsequent validation by qRT-PCR and immunohistochemical staining in clinical specimens confirmed the value of the risk score in predicting the prognosis. We developed a 12-gene signature that could predict the prognosis of HCC patients. This signature is of high precision and would help identifying subgroups of HCC patients with high or low risk of unfavorable survival.

Drug Repurposing for COVID-19 by Constructing a Comorbidity Network with Central Nervous System Disorders.

In the post-COVID-19 era, treatment options for potential SARS-CoV-2 outbreaks remain limited. An increased incidence of central nervous system (CNS) disorders has been observed in long-term COVID-19 patients. Understanding the shared molecular mechanisms between these conditions may provide new insights for developing effective therapies. This study developed an integrative drug-repurposing framework for COVID-19, leveraging comorbidity data with CNS disorders, network-based modular analysis, and dynamic perturbation analysis to identify potential drug targets and candidates against SARS-CoV-2. We constructed a comorbidity network based on the literature and data collection, including COVID-19-related proteins and genes associated with Alzheimer's disease, Parkinson's disease, multiple sclerosis, and autism spectrum disorder. Functional module detection and annotation identified a module primarily involved in protein synthesis as a key target module, utilizing connectivity map drug perturbation data. Through the construction of a weighted drug-target network and dynamic network-based drug-repurposing analysis, ubiquitin-carboxy-terminal hydrolase L1 emerged as a potential drug target. Molecular dynamics simulations suggested pregnenolone and BRD-K87426499 as two drug candidates for COVID-19. This study introduces a dynamic-perturbation-network-based drug-repurposing approach to identify COVID-19 drug targets and candidates by incorporating the comorbidity conditions of CNS disorders.

Development and validation of a prospective questionnaire for assessing oily sensitive skin.

BACKGROUND: Skin type has a strong influence on how sensitive skin develops, with oily skin accounting for a larger proportion of sensitive skin. However, there has not been a scientifically sound questionnaire for determining oily sensitive (OS)-type skin in prior studies. OBJECTIVES: In order to identify OS-type skin in the general population, we therefore intend to create an OS-type skin evaluation questionnaire, develop various thresholds through data analysis and classify skin based on two dimensions of sensitivity and oiliness. METHODS: A questionnaire with questions regarding subjects' basic information, skin oiliness and skin sensitivity was given to each individual who participated in the study (n = 1297). To define the thresholds for OS-type skin, receiver-operating characteristic (ROC) curves were generated. The results of the lactic acid stinging test (LAST) and noninvasive instrument information obtained were compared with the thresholds mentioned above to verify the effectiveness of this tool. RESULTS: According to the ROC curves, questionnaire cut-off values of 11.5, 20.5 and 29.5 can be used to detect mildly, moderately and severely sensitive skin, respectively. In addition, the questionnaire cut-off values of 22.5 and 31.5 can be used to detect moderately and severely oily skin, respectively. According to our study, the four sensitive-skin groups' LAST scores differed significantly from one another, while the skin sebum levels differed significantly between the three oily groups. Additionally, the EI and LAST scores were significantly correlated with skin sensitivity levels, whereas sebum, moisture and EI were positively correlated with skin oiliness levels. CONCLUSIONS: We developed an OS-type skin evaluation questionnaire that has been tested and shown scientifically to be a promising method for evaluating OS-type skin and to completely examine the traits of sensitive and oily skin.

CONTEXTE: Le type de peau a une forte influence sur la sensibilité de la peau, avec une peau grasse représentant une plus grande proportion de peaux sensibles. Cependant, il n'y a pas eu de questionnaire scientifiquement fiable pour déterminer le type de peau sensible grasse (OS) dans les études antérieures. OBJECTIFS: Afin d'identifier la peau grasse et sensible dans la population générale, nous avons donc l'intention de créer un questionnaire d'évaluation de la peau grasse et sensible, d'élaborer différents seuils par l'analyse des données et de catégoriser à partir de deux dimensions de sensibilité et d'état huileux. MÉTHODES: Un questionnaire comprenant des questions sur les informations de base des sujets, la sécrétion de sébum de la peau et la sensibilité cutanée a été distribué à chaque individu ayant participé à l'étude (n = 1297). Pour définir les seuils des peaux grasse et sensible, des courbes sensibilité/spécificité (receiver­operating characteristic, ROC) ont été générées. Les résultats du test de picotement à l'acide lactique (LAST) et les informations obtenues à l'aide d'instruments non invasifs ont été comparés aux seuils mentionnés ci­dessus pour vérifier l'efficacité de cet outil. RÉSULTATS: Selon les courbes ROC, des valeurs limites du questionnaire de 11,5, 20,5 et 29,5 peuvent être utilisées pour détecter une sensibilité cutanée légère, modérée et sévère, respectivement. De plus, les valeurs de seuil du questionnaire de 22,5 et 31,5 peuvent être utilisées pour détecter respectivement une peau modérément et sévèrement grasse. Selon notre étude, les scores LAST des quatre groupes à peau sensible différaient significativement les uns des autres, tandis que les taux de sébum cutané différaient significativement entre les trois groupes à peau grasse. De plus, les scores IE et LAST étaient significativement corrélés avec les taux de sensibilité cutanée, tandis que le sébum, l'humidité et l'IE étaient positivement corrélés avec les taux de graisse cutané. CONCLUSIONS: Nous avons développé un questionnaire d'évaluation de la peau grasse et sensible qui a été testé et qui s'est avéré scientifiquement être une méthode prometteuse pour évaluer la peau grasse et sensible et pour examiner complètement les caractéristiques de la peau sensible et grasse.

Serum levels of specific IgE to cow's milk and its components as predictors of anaphylaxis in Chinese children with cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in predicting anaphylaxis. OBJECTIVE: To explore risk factors for anaphylaxis and to determine practical cut-offs for allergic tests in predicting anaphylaxis. METHODS: This is a prospective cohort study. Children with IgE-mediated CMA were enrolled and divided into three groups (Group 1: non-anaphylaxis; Group 2: GRADE I anaphylaxis; Group 3: GRADE II-IV anaphylaxis that warranted epinephrine). Prick-to-prick tests (PTPs) using fresh cow's milk (CM) were performed. Serum specific IgE (sIgE) against CM and its components, including casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin were measured. The 90% and 95% positive predictive value (PPV) decision points for predicting anaphylaxis were determined. Potential predictors of anaphylaxis were evaluated in logistic regression models. RESULTS: This study included 134 CMA patients with a median age of 14.4 months. The sensitization rate to any CM component was 89%. Group 3 was more likely to be sensitized to multiple CM components and have higher sIgE levels. The 95% PPV diagnostic decision points of casein-sIgE in predicting anaphylaxis was 13.0 kUA/L. For GRADE II-IV anaphylaxis, casein-sIgE ≥ 54.9 kUA/L could provide a PPV of 88.9%. The elevated casein-sIgE level (OR 14.0, P=0.025) and complicating respiratory allergic diseases (OR 4.8, P=0.022) were independent risk factors for GRADE II-IV anaphylaxis. CONCLUSION: High casein-sIgE levels are strongly associated with CM anaphylaxis. Detection of casein-sIgE may offer an additional value for the prediction of CM anaphylaxis.

Comparison of Disease Severity, Anxiety and Depression in Obsessive-Compulsive Disorder Patients with Different Insight.

BACKGROUND: Significant individual differences exist in the insight of patients with obsessive-compulsive disorder (OCD), and the clinical characteristics of OCD patients with varying levels of insight are not entirely uniform. This study aims to investigate disparities in disease severity, anxiety, and depression status among OCD patients with differing levels of insight, with the goal of generating novel treatment strategies for OCD. METHODS: A total of 114 patients diagnosed with OCD were recruited from the Department of Psychology at Affiliated Mental Health Center & Hangzhou Seventh People's Hospital to participate in this research. Based on their Total Insight and Treatment Attitude Questionnaire (ITAQ) scores, the patients were divided into two groups: Group OCD with high insight (referred to as Group OCD-HI, ITAQ score ≥20 points, n = 80) and Group OCD with low insight (referred to as Group OCD-LI, ITAQ score <20 points, n = 34). Subsequently, the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) scores were compared between the two groups. All questionnaires for this study were completed by experienced psychiatrists. RESULTS: The Y-BOCS scores for YB1, YB2, YB4, YB5, YB6, YB9, and the total Y-BOCS scores in Group OCD-HI were significantly higher than those in Group OCD-LI (p < 0.05). Conversely, Group OCD-HI exhibited significantly lower HAMA and HAMD scores compared to Group OCD-LI (p < 0.05). Furthermore, the total ITAQ score displayed a significant negative correlation with the total Y-BOCS, HAMA, and HAMD scores (p < 0.05). CONCLUSIONS: This study revealed that certain OCD patients exhibit incomplete insight, and this lack of insight is strongly associated with increased disease severity and heightened levels of anxiety and depression. It is hoped that by enhancing the insight of OCD patients, the goal of ameliorating disease symptoms and alleviating negative emotions can be attained.

Synthesis of Multifunctional Organic Molecules via Michael Addition Reaction to Manage Perovskite Crystallization and Defect.

Additive engineering plays a pivotal role in achieving high-quality light-absorbing layers for high-performance and stable perovskite solar cells (PSCs). Various functional groups within the additives exert distinct regulatory effects on the perovskite layer. However, few additive molecules can synergistically fulfill the dual functions of regulating crystallization and passivating defects. Here, we custom-synthesized 2-ureido-4-pyrimidone (UPy) organic small molecules with diverse functional groups as additives to modulate crystallization and defects in perovskite films via the Michael addition reaction. Theoretical and experimental investigations demonstrate that the -OH groups in UPy exhibit significant effects in fixing uncoordinated Pb2+ ions, passivation of lead-iodide antisite defects, alleviating hysteresis, and reducing non-radiative recombination. Furthermore, the enhanced C=O and -NH2 motifs interact with the A-site cation via hydrogen bonding, which relieves residual strain and adjusts crystal orientation. This strategy effectively controls perovskite crystallization and passivates defects, ultimately enhancing the quality of perovskite films. Consequently, the open-circuit voltage of the UPy-based p-i-n PSCs reaches 1.20 V, and the fill factor surpasses 84 %. The champion device delivers a power conversion efficiency of 25.75 %. Remarkably, the unencapsulated device maintained 96.9 % and 94.5 % of its initial efficiency following 3,360 hours of dark storage and 1,866 hours of 1-sun illumination, respectively.

Preoperative Diagnosis of Dual-Phenotype Hepatocellular Carcinoma Using Enhanced MRI Radiomics Models.

BACKGROUND: Dual-phenotype hepatocellular carcinoma (DPHCC) is highly aggressive and difficult to distinguish from hepatocellular carcinoma (HCC). PURPOSE: To develop and validate clinical and radiomics models based on contrast-enhanced MRI for the preoperative diagnosis of DPHCC. STUDY TYPE: Retrospective. POPULATION: A total of 87 patients with DPHCC and 92 patients with non-DPHCC randomly divided into a training cohort (n = 125: 64 non-DPHCC; 61 DPHCC) and a validation cohort (n = 54: 28 non-DPHCC; 26 DPHCC). FIELD STRENGTH/SEQUENCE: A 3.0 T; dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging sequence. ASSESSMENT: In the clinical model, the maximum tumor diameter and hepatitis B virus (HBV) were independent risk factors of DPHCC. In the radiomics model, a total of 1781 radiomics features were extracted from tumor volumes of interest (VOIs) in the arterial phase (AP) and portal venous phase (PP) images. For feature reduction and selection, Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were used. Clinical, AP, PP, and combined radiomics models were established using machine learning algorithms (support vector machine [SVM], logistic regression [LR], and logistic regression-least absolute shrinkage and selection operator [LR-LASSO]) and their discriminatory efficacy assessed and compared. STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Chi-square test, regression analysis, receiver operating characteristic curve (ROC) analysis, Pearson correlation analysis, the Delong test. A P value < 0.05 was considered statistically significant. RESULTS: In the validation cohort, the combined radiomics model (area under the curve [AUC] = 0.908, 95% confidence interval [CI]: 0.831-0.985) showed the highest diagnostic performance. The AUCs of the PP (AUC = 0.879, 95% CI: 0.779-0.979) and combined radiomics models were significantly higher than that of clinical model (AUC = 0.685, 95% CI: 0.526-0.844). There were no significant differences in AUC between AP or PP radiomics model and combined radiomics model (P = 0.286, 0.180 and 0.543). CONCLUSION: MRI radiomics models may be useful for discriminating DPHCC from non-DPHCC before surgery. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Two-Dimensional Cu-Porphyrin Metal-Organic Framework Nanosheet-Supported Flaky TiO2 as an Efficient Visible-Light-Driven Photocatalyst for Dye Degradation and Cr(VI) Reduction.

A series of 2D M(Cu, Zn, Co, and Mn)-TCPP MOFs/TiO2 binary nanocomposites (TCPP = tetrakis(4-carboxyphenyl)porphyrin) were constructed by solvothermal in situ loading of flaky TiO2 on the surface of 2D metal-organic frameworks (MOFs). The influence of different coordination metals on the catalytic activity was studied, and it was found that the 2D Cu-TCPP MOFs/TiO2 nanocomposite exhibited the best photo-Fenton performance. The superior property can be attributed to the high absorption coefficient and ultrathin two-dimensional structure of the 2D Cu-TCPP MOFs nanosheets. Meanwhile, the 2D Cu-TCPP MOFs/TiO2 II heterostructure can effectively promote the separation and transfer of photoformed carriers. Moreover, under visible irradiation, the optimized 2D Cu-TCPP MOFs/TiO2 composite can convert 99.9% of Cr(VI) to Cr(III) within 60 min with methanol as the hole scavenger at pH 3.14. Also, the photocatalytic performance of 2D Cu-TCPP MOFs/TiO2 was maintained after five reaction cycles. Furthermore, the proposed visible-light-driven photocatalysis mechanism of the 2D Cu-MOFs/TiO2 composite was reasonably derived according to experimental results. This study demonstrates the potential of building efficient TiO2-based visible light photocatalysts with 2D metal-porphyrin MOFs.

Metal-Controlled Switchable Regioselective Synthesis of Substituted Imidazoles and Pyrroles via Ring Opening/Cyclocondensation with 2H-Azirines.

Catalytic selective annulation of 2H-azirines constitutes a general and modular strategy for the generation of molecular complexity. By using Pd-catalyzed ring opening/heterocyclization associated with direct cleavage of C-N and C-C bonds under appropriate conditions, the formation of imidazoles is presented. Alternatively, the silver-catalyzed radical [3 + 2] cycloannulation of 2H-azirines and 1,3-dicarbonyl compounds provides highly functionalized pyrrole derivatives. Both aliphatic cyclic and acyclic diketones are tolerated with good regioselectivity. Moreover, a radical capture experiment was carried out to determine the proposed mechanism, providing support for a facile radical process.

Synthesis of (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-ones from (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oximes and iodobenzenes via a palladium-catalyzed dearomative arylation/oxidation reaction.

A new method has been successfully developed that offers a facile and reliable approach for synthesizing (E)-2-(1-(methoxyimino)ethyl)-2-phenylbenzofuran-3(2H)-one, providing 28 compounds. This optimized process enables efficient preparation of a wide range of compounds using readily available (E)-1-(benzofuran-2-yl)ethan-1-one O-methyl oxime and iodobenzene, and provides alternative ideas for the structural modification of benzofuran ketones.

The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.

Chronic myeloid leukaemia (CML) is driven by the activity of the BCR-ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Studies in patients with chronic-phase CML have shown that around 50% of patients who achieve and maintain undetectable BCR-ABL1 transcript levels for at least 2 years remain disease-free after the withdrawal of treatment. Here we characterize ABL001 (asciminib), a potent and selective allosteric ABL1 inhibitor that is undergoing clinical development testing in patients with CML and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia. In contrast to catalytic-site ABL1 kinase inhibitors, ABL001 binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation. ABL001 and second-generation catalytic inhibitors have similar cellular potencies but distinct patterns of resistance mutations, with genetic barcoding studies revealing pre-existing clonal populations with no shared resistance between ABL001 and the catalytic inhibitor nilotinib. Consistent with this profile, acquired resistance was observed with single-agent therapy in mice; however, the combination of ABL001 and nilotinib led to complete disease control and eradicated CML xenograft tumours without recurrence after the cessation of treatment.

Effect of Night Shift Work in Clinical Laboratories on Pediatric Complete Blood Count Results.

BACKGROUND: There has been much research into the impact of shift systems on clinicians and nurses, but little research into quality control in clinical laboratories. This topic focuses on assessing the impact of shift systems on clinical laboratory scientists. METHODS: A total of 34,955 CBCs from pediatric patients who visited the hospital during night-time hours over a period of three years were selected for analysis. The quality of routine blood tests was evaluated using four indica-tors: red blood cell count, white blood cell count, platelet count, and hemoglobin levels. The effects of gender, years of experience, and length of the night shift on test results were evaluated separately for each clinical laboratory scientist. RESULTS: The results showed that the gender and years of experience of the clinical laboratory scientists did not affect the CBC results. However, a significant impact was observed as the number of hours worked on night shifts increased. CONCLUSIONS: The findings of this study suggest that the night shift schedule of clinical laboratory scientists can have an impact on the accuracy of pediatric CBCs. It is essential for healthcare institutions to consider the length of night shifts for clinical laboratory scientists and implement measures to minimize the impact on test results.

Comparison of supercritical fluid chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry for the stereoselective analysis of chlorfenvinphos and dimethylvinphos in tobacco.

This study used reversed-phase liquid chromatography-tandem mass spectrometry and supercritical fluid chromatography-tandem mass spectrometry for determination of the stereoisomers of chlorfenvinphos and dimethylvinphos in tobacco. Tobacco samples were extracted and purified with a modified quick, easy, cheap, effective, rugged, and safe technique using spherical carbon. The performance of both methodologies was comprehensively compared in terms of methods validation parameters (separation efficiency, linearity, selectivity, recovery, repeatability, sensitivity, matrix effect, etc.). Under optimized conditions, the calibration curves of the stereoisomers of chlorfenvinphos and dimethylvinphos in the range of 10-500 ng/mL showed excellent linearity with R2 ≥ 0.997 in both methods. The adequate recoveries of analytes from three different spiked tobaccos were obtained using reversed-phase liquid chromatography-tandem mass spectrometry (86.1-95.7%) as well as supercritical fluid chromatography-tandem mass spectrometry (86.5-94.0%). The relative standard deviations for spiked samples were all below 7.0%. Compared with supercritical fluid chromatography-tandem mass spectrometry, lower matrix effects and LODs can be obtained in reversed-phase liquid chromatography-tandem mass spectrometry.