Proteomic and phosphoproteomic landscape of localized prostate cancer unveils distinct molecular subtypes and insights into precision therapeutics.

Building upon our previous investigation of genomic, epigenomic, and transcriptomic profiles of prostate cancer in China, we conducted a comprehensive analysis of proteomic and phosphoproteomic profiles of 82 tumor tissues and matched adjacent normal tissues from 41 Chinese patients with localized prostate cancer. We identified three distinct proteomic subtypes with significant difference in both molecular features and clinical prognosis. Notably, these proteomic subtypes exhibited a parallel degree of heterogeneity in the phosphoproteome, featuring unique metabolism, proliferation, and immune infiltration characteristics. We further demonstrated that a combination of proteins and phosphosites serves as the most effective biomarkers in prostate cancer to predict biochemical recurrence. Through an integrated multiomics analysis, we revealed mechanistic differences underlying different proteomic subtypes and highlighted the potential significance of Serine/arginine-rich splicing factor 1 (SRSF1) phosphorylation in promoting the malignant characteristics of prostate cancer cells. Our multiomics data provide valuable resources for understanding the molecular mechanisms of prostate cancer within the Chinese population, which have the potential to inform the development of personalized treatment strategies and enhance prognostic analyses for prostate cancer patients.

Relationship between temperature and acute myocardial infarction: a time series study in Xuzhou, China, from 2018 to 2020.

BACKGROUND: It is widely known that the incidence rate and short-term mortality of acute myocardial infarctions (AMIs) are generally higher during the winter months. The goal of this study was to determine how the temperature of the environment influences fatal acute myocardial infarctions in Xuzhou. METHODS: This observational study used the daily meteorological data and the data on the cause of death from acute myocardial infarction in Xuzhou from January 1, 2018, to December 31, 2020. After controlling meteorological variables and pollutants, the distributed nonlinear lag model (DLNM) was used to estimate the correlation between temperature and lethal AMI. RESULTS: A total of 27,712 patients with fatal AMI were enrolled. 82.4% were over the age of 65, and 50.9% were men. Relative to the reference temperature (15 ℃), the 30-day cumulative RRs of the extremely cold temperature (- 2 ℃) for the general population, women, and people aged 65 years and above were 4.66 (95% CI: 1.76, 12.30), 15.29 (95% CI: 3.94, 59.36), and 7.13 (95% CI: 2.50, 20.35), respectively. The 30-day cumulative RRs of the cold temperature (2 ℃) for the general population, women, and people aged 65 years and above were 2.55 (1.37, 4.75), 12.78 (2.24, 5.36), and 3.15 (1.61, 6.16), respectively. No statistically significant association was observed between high temperatures and the risk of fatal AMI. The influence of the cold effect (1st and 10th) was at its peak on that day, and the entire cold effect persisted for 30 days. Temperature extremes had an effect on the lag patterns of distinct age and gender stratifications. CONCLUSION: According to this study, the risk of fatal AMI increases significantly in cold weather but not in hot weather. Women above the age of 65 are particularly sensitive to severe weather events. The influence of frigid weather on public health should also be considered.

Serum taurine affects lung cancer progression by regulating tumor immune escape mediated by the immune microenvironment.

INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

Systematic Evaluation of Guidelines for the Diagnosis and Treatment of Hepatitis E Virus Infection.

Background and Aims: The hepatitis E virus (HEV) is a zoonotic disease, and infection with HEV in humans primarily causes acute infections and can progress to chronic manifestation in immunocompromised individuals. Over the past decade, guidelines for diagnosing and treating HEV infection have been developed. This study aimed to systematically assess the quality of current guidelines for diagnosing and treating HEV infection, and we analyzed the differences in guideline quality and primary recommendations and explored possible reasons for these differences. Methods: Guidelines published between 2013 and 2022 were searched, and studies were identified using selection criteria. The study assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation tool, extracted the primary recommendations in the guidelines, determined the highest level of evidence supporting the recommendations, and reclassified the evidence using the Oxford Centre for Evidence-Based Medicine grading system. Results: Seven guidelines were included in the final analysis. The quality of the guidelines varied widely. The discrepancies may have been caused by the lack of external experts, the failure to consider influencing factors in guideline application, and the lack of consideration of the public's opinion. Analysis of the heterogeneity in primary recommendations revealed differences in algorithms for managing chronic HEV infection, the dosage of ribavirin, and a low level of evidence supporting the primary recommendations. Conclusions: Guideline quality and primary recommendations vary considerably. Refinement by guideline developers and researchers would facilitate updating and applying guidelines for diagnosing and treating HEV infection.

Data-Driven Insights into the Contamination of Polycyclic Aromatic Hydrocarbons in Marine Bays.

The synthesis of polycyclic aromatic hydrocarbon (PAH) data allows us to quantify and gain insights into the spatiotemporal dynamics of PAH contamination in marine bays. Here, a data synthesis framework was developed to understand data-driven insights into the spatiotemporal levels, compositional profiles, and potential sources of PAHs in water and sediment of marine bays. PAHs were detected in 69 bays worldwide, with contamination hotspots located in Asian bays. PAH concentrations in pre-2000 were significantly lower than those in the 2000s and post-2010, while the dominant species in water and sediment were 2-3 ring and 4-6 ring PAHs, respectively. The composition patterns of PAHs included 2-3 ring, 3-5 ring, and 4-5 ring dominant categories, but no significant distance decay relationship was found in the composition similarity due to international energy trade. Temporal dynamic patterns of concentrations included Descending-, Ascending-, and Inverted V-type, whereas over longer time spans, the pattern is more similar to the Inverted V-type owing to the reductions in emission intensity. PAHs were derived from both petrogenic and pyrolytic sources, with combustion from both coal and petroleum being the dominant source. These data-driven discoveries provide quantitative insights into the spatiotemporal patterns in the concentration and composition of PAHs, contributing to the mitigation of PAH contamination.

The feasibility of targeted axillary dissection for breast cancer axillary surgery de-escalation after neoadjuvant therapy: A prospective cohort study.

PURPOSE: Targeted axillary dissection (TAD) after neoadjuvant therapy (NAT) includes removing of marked and sentinel lymph nodes (SLNs). The aim was to investigate the optimization of TAD localization techniques after NAT among breast cancer patients. METHODS: From November 2020 to 2022, we prospectively enrolled 107 lymph node-positive breast cancer patients in XX Hospital and received complete cycles of NAT. Patients were randomly divided into the following 3 groups before treatment: group A, marked node with clip (n=34); group B, marked node with 125I seed (n=32); and group C, marked node with clip and 125I seed (n=41). Dual tracers were used to search for SLNs after NAT. The main endpoint was the detection rate of marked nodes and false-negative rate (FNR). RESULTS: The detection rates using the TAD localization technique were 82.6% (28/34), 100% (32/32), and 100% (41/41) for groups A, B, and C, respectively (P>0.05). The FNR rates were 15.8%, 5.9%, and 5.6% among group A, B, and C, respectively (P>0.05). The FNR rates in cN1 patients were 5.1%, 2.7%, and 2.6%, among these three groups, respectively (P>0.05). The change in distance between 125I seeds and clips in axillary lymph nodes was <3 mm. The FNR rates of TAD guided by dye tracer, radiolabeled tracer, and dual tracers were 5.4%, 5.2%, and 3.4%, respectively (P>0.05). The negative predictive values were 93.0%, 93.0%, and 95.2%, respectively (P>0.05). CONCLUSION: Considering inexpensive and detect rate of 125I seeds, it is recommended that placement of 125I seeds to localize metastatic nodes in neoadjuvant setting. The TAD guided by dye tracer is also feasible for axillary de-escalation surgery after NAT in countries or regions without radiolabeled colloid.

Urinary cytologic features of primitive neuroectodermal tumor primarily involving the kidney: A case report.

Renal primitive neuroectodermal tumor(rPNET) is an extremely rare and distinct entity that can be mistaken for a variety of other round cell tumors. Findings from fine needle aspiration cytology have been reported, but there have been no reports of PNET cytomorphological features in urine cytology specimen. Here, we report a case of PNET characterized by urine cytology. A 24-year-old girl presented with hematuria for half a month. Computed tomography showed a large tumor involving the upper pole of the right kidney. Urinary cytology exhibited highly cellular clusters composed of small, round, atypical cells with little cytoplasm and a high nuclear/cytoplasmic ratio. Following a right nephrectomy, the biopsy confirmed the diagnosis of rPNET. Additionally, immunohistochemistry (IHC) staining of the decolorized liquid-based cytology slide was positive for CD99, further confirming the diagnosis through urine cytology. Our observations suggest that urinary cytology in combination with cytological morphology and immunocytochemistry may be a potentially useful method for the detection of PNET.

The neutrophil extracellular traps in neurological diseases: An update.

Neutrophil extracellular traps released by neutrophils are web-like DNA structures adhered to granulin proteins with bactericidal activity and can be an important mechanism for preventing pathogen dissemination or eliminating microorganisms. However, they also play important roles in diseases of other systems, such as the central nervous system. We tracked the latest advances and performed a review based on published original and review articles related to neutrophil extracellular traps and neurological diseases. Generally, neutrophils barely penetrate the blood-brain barrier into the brain parenchyma, but when pathological changes such as infection, trauma, or neurodegeneration occur, neutrophils rapidly infiltrate the central nervous system to exert their defensive effects. However, neutrophils may adversely affect the host when they uncontrollably release neutrophil extracellular traps upon persistent neuroinflammation. This review focused on recent advances in understanding the mechanisms and effects of neutrophil extracellular traps release in neurological diseases, and we also discuss the role of molecules that regulate neutrophil extracellular traps release in anticipation of clinical applications in neurological diseases.

The predictive value of estimated pulse wave velocity (ePWV) combined with BMI for newly diagnosed diabetes.

PURPOSE: Estimated pulse wave velocity (ePWV) and body mass index (BMI) are significant predictors of new-onset diabetes. This study aims to evaluate the impact and predictive value of combining ePWV and BMI on the incidence of new-onset diabetes. METHODS: A secondary analysis was conducted on a cohort study by Rich Healthcare (China), involving 211,833 eligible participants. Logistic regression analysis identified factors influencing diabetes occurrence, while ROC curve analysis assessed the predictive value of ePWV, BMI, and their combination for new-onset diabetes. RESULTS: Over a mean follow-up period of 3.12 years, 3,000 men (1.41%) and 1,174 women (0.55%) were diagnosed with diabetes. Logistic regression revealed that BMI, triglycerides, alanine aminotransferase, blood urea nitrogen, creatinine clearance rate, ePWV, and family history of diabetes are high-risk factors for new-onset diabetes. The combination of ePWV and BMI provided a higher area under the ROC curve (0.822) compared to ePWV or BMI alone. CONCLUSION: Elevated levels of ePWV and BMI are independent risk factors for new-onset diabetes. Combining these measures enhances predictive accuracy compared to using either indicator alone.

Ac2-26 Reduced Lung Injury After Cardiopulmonary Bypass via the AKT1/GSK3ß/eNOS Pathway.

INTRODUCTION: Cardiopulmonary bypass (CPB) leads to severe inflammation and lung injury. Our previous study showed that Ac2-26 (an active n-terminal peptide of Annexin A1) can reduce acute lung injury. The aim of this study was to evaluate the effect of Ac2-26 on lung injury in CPB rats. METHODS: Forty rats were randomly divided into the sham, CPB, Ac, Ac/serine/threonine kinase 1 (AKT1), and Ac/ glycogen synthase kinase (GSK)-3ß groups. The rats in the sham group only received anesthesia, intubation, and cannulation. The rats in the other 4 groups received the standard CPB procedure. The rats in the CPB, Ac, Ac/AKT1, and Ac/GSK3ß groups were immediately injected with saline, Ac2-26 (1 mg/kg), Ac2-26 combined with short hairpin RNA (AKT1), or Ac2-26 combined with a GSK3ß inhibitor after CPB. At 12 h after the end of CPB, the PaO2/ fraction of inspired oxygen ratio, wet/dry weight ratio and protein content in the bronchoalveolar lavage fluid (BALF) were recorded. The numbers of macrophages and neutrophils in the BALF and blood were determined. Cytokine levels in the blood and BALF were investigated. Lung tissue histology and apoptosis were estimated. The expression of nuclear factor kappa- B, AKT1, GSK3ß, endothelial nitric oxide synthase and apoptosis-related proteins was analyzed. The survival of all the rats was recorded. RESULTS: Compared with the rats in the sham group, all the parameters examined worsened in the rats that received CPB. Compared with those in the CPB group, Ac2-26 significantly improved pulmonary capillary permeability, reduced cytokine levels, and decreased histological scores and apoptosis. The protective effect of Ac2-26 on lung injury was significantly reversed by AKT1 short hairpin RNA or a GSK3ß inhibitor. CONCLUSIONS: Ac2-26 significantly reduced lung injury and inflammation after CPB. The protective effect of Ac2-26 mainly depended on the AKT1/GSK3ß/endothelial nitric oxide synthase pathway.

Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3ß/eNOS pathway.

OBJECTIVE: About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB. METHODS: A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated. RESULTS: Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3ß and eNOS, and this promotion was inhibited by the shRNA. CONCLUSION: The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3ß/eNOS.

Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes.

Early insulin therapy is capable to achieve glycemic control and restore ß-cell function in newly diagnosed type 2 diabetes (T2D), but its effect on cardiovascular outcomes in these patients remains unclear. In this nationwide real-world study, we analyzed electronic health record data from 19 medical centers across China between 1 January 2000, and 26 May 2022. We included 5424 eligible patients (mean age 56 years, 2176 women/3248 men) who were diagnosed T2D within six months and did not have prior cardiovascular disease. Multivariable Cox regression models were used to estimate the associations of early insulin therapy (defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients) with the incidence of major cardiovascular events including coronary heart disease (CHD), stroke, and hospitalization for heart failure (HF). During 17,158 persons years of observation, we documented 834 incident CHD cases, 719 stroke cases, and 230 hospitalized cases for HF. Newly diagnosed T2D patients who received early insulin therapy, compared with those who did not receive such treatment, had 31% lower risk of incident stroke, and 28% lower risk of hospitalization for HF. No significant difference in the risk of CHD was observed. We found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting models. These findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

Topological valley Hall polariton condensation.

A photonic topological insulator features robust directional propagation and immunity to defect perturbations of the edge/surface state. Exciton-polaritons, that is, the hybrid quasiparticles of excitons and photons in semiconductor microcavities, have been proposed as a tunable nonlinear platform for emulating topological phenomena. However, mainly due to excitonic material limitations, experimental observations so far have not been able to enter the nonlinear condensation regime or only show localized condensation in one dimension. Here we show a topological propagating edge state with polariton condensation at room temperature and without any external magnetic field. We overcome material limitations by using excitonic CsPbCl3 halide perovskites with a valley Hall lattice design. The polariton lattice features a large bandgap of 18.8 meV and exhibits strong nonlinear polariton condensation with clear long-range spatial coherence across the critical pumping density. The geometric parameters and material composition of our nonlinear many-body photonic system platform can in principle be tailored to study topological phenomena of other interquasiparticle interactions.

Association between Body Iron Status and Cognitive Task Performance in a Nationally Representative Sample of Older Adults.

Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.

Ac2-26 activated the AKT1/GSK3ß pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats. METHODS: Forty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups were injected with shRNA, inhibitor and agonist of GSK3ß respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein ß(S100ß) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected. RESULTS: Compared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3ß. The agonist of GSK3ß recovered the protection of Ac2-26 in presence of shRNA. CONCLUSIONS: Ac2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3ß pathway.

Genome-Wide Identification and Hormone Response Analysis of the COBL Gene Family in Barley.

Barley (Hordeum vulgare L.), a diverse cereal crop, exhibits remarkable versatility in its applications, ranging from food and fodder to industrial uses. The content of cellulose in barley is significantly influenced by the COBRA genes, which encode the plant glycosylphosphatidylinositol (GPI)-anchored protein (GAP) that plays a pivotal role in the deposition of cellulose within the cell wall. The COBL (COBRA-Like) gene family has been discovered across numerous species, yet the specific members of this family in barley remain undetermined. In this study, we discovered 13 COBL genes within the barley genome using bioinformatics methods, subcellular localization, and protein structure analysis, finding that most of the barley COBL proteins have a signal peptide structure and are localized on the plasma membrane. Simultaneously, we constructed a phylogenetic tree and undertook a comprehensive analysis of the evolutionary relationships. Other characteristics of HvCOBL family members, including intraspecific collinearity, gene structure, conserved motifs, and cis-acting elements, were thoroughly characterized in detail. The assessment of HvCOBL gene expression in barley under various hormone treatments was conducted through qRT-PCR analysis, revealing jasmonic acid (JA) as the predominant hormonal regulator of HvCOBL gene expression. In summary, this study comprehensively identified and analyzed the barley COBL gene family, aiming to provide basic information for exploring the members of the HvCOBL gene family and to propose directions for further research.

Does the Cognitive Reflection Test Work with Chinese College Students? Evidence from a Time-Limited Study.

The cognitive reflection test (CRT) is an experiment task commonly used in Western countries to test intuitive and analytical thinking styles. However, the validity of this task for Chinese participants has not been explored. Therefore, this study recruited Chinese college students to finish CRT tasks with various experimental designs. To gauge the accuracy of the CRT tasks, 438 Chinese college students first completed online questionnaires. Participants were then invited to participate in an offline laboratory with the same experimental settings. Finally, time pressure was used to strictly control intuition and analytical thinking to explore the performance of Chinese college students on CRT tasks. The results show that of the three experiments, Chinese college students had the highest accuracy in the offline test, and the CRT's intuitive conflict problem still applies to Chinese students under the time-limited condition. This study demonstrates the validity of the CRT in China and proves that time pressure is an effective method for identifying individuals with strong logic ability.

Association of cerebral palsy with autism spectrum disorder and attention-deficit/hyperactivity disorder in children: a large-scale nationwide population-based study.

OBJECTIVE: To examine the association of cerebral palsy with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), providing evidence for interdisciplinary medical service for children with cerebral palsy. DESIGN: A large-scale nationwide population-based study. SETTING: The National Health Interview Survey (NHIS). PATIENTS: 177 899 children aged 3-17 years among NHIS participants from 1997 to 2003 and 2008 to 2018. RESULTS: Among the 177 899 children included in this analysis, 602 (0.33%) had cerebral palsy, 1997 (1.16%) had ASD, and 13 697 (7.91%) had ADHD. Compared with children without cerebral palsy, children with cerebral palsy had a higher prevalence of ASD (6.09% vs 1.15%; p<0.001) and ADHD (15.91% vs 7.89%; p<0.001). After adjustment for age, sex, race/ethnicity, family highest education level, family income level and geographical region, the OR among children with cerebral palsy, compared with children without cerebral palsy, was 5.07 (95% CI 3.25 to 7.91) for ASD (p<0.001) and 1.95 (95% CI 1.43 to 2.66) for ADHD (p<0.001). Furthermore, the association of cerebral palsy with ASD and ADHD remained significant in all subgroups stratified by age, sex and race. CONCLUSION: In a large, nationally representative sample of US children, this study shows that children with cerebral palsy are at an increased risk of ASD and ADHD.

Exposure to Polybrominated Diphenyl Ethers and Risk of All-Cause and Cause-Specific Mortality.

Importance: Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. Objective: To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. Design, Setting, and Participants: This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. Exposures: PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. Main Outcomes and Measures: All-cause mortality, cancer mortality, and cardiovascular mortality. Results: This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. Conclusions and Relevance: In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.

Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC). Organoid-formation assays and in vivo lineage tracing experiments demonstrate that Zeb1+ epithelioid cells are putative cells of origin for NEPC. Mechanistically, Zeb1 transcriptionally regulates the expression of several key glycolytic enzymes, thereby predisposing tumor cells to utilize glycolysis for energy metabolism. During this process, lactate accumulation-mediated histone lactylation enhances chromatin accessibility and cellular plasticity including induction of neuro-gene expression, which promotes NEPC development. Collectively, Zeb1-driven metabolic rewiring enables the epigenetic reprogramming of prostate cancer cells to license the adeno-to-neuroendocrine lineage transition.