Effect of impregnation strategy on structural characteristics of Ce-Mn/Al2O3 and its catalytic ozonation of benzoic acid.

Ce-Mn binary oxides supported on Al2O3 (Ce-Mn/Al2O3), with enhanced activity and stability for catalytic ozonation of benzoic acid, were synthesized using a facile impregnation method. The competitive synergetic effects between cerium and manganese significantly influenced the structural characteristics and catalytic performance of the catalysts depending on the impregnation sequence. Catalysts prepared via the one-step impregnation process exhibited a higher concentration of homogeneous Ce3+ species on the catalyst surface. This led to an increase in surface oxygen vacancies, thereby enhancing catalytic activity. In contrast, the two-step impregnation process resulted in fewer oxygen vacancies due to reduced competitive effects between cerium and manganese. Overall, the optimized Ce-Mn/Al2O3 catalysts demonstrated improved catalytic performance in ozonation reactions, highlighting the importance of impregnation method and calcination conditions in tailoring catalyst properties for enhanced activity and stability. Oxygen vacancies play a crucial role as active sites for ozone adsorption and dissociation into *O2 and *O, facilitated by the reduction of Mn4+ to Mn3+ and the oxidation of Ce3+ to Ce4+. This process forms an electron closed loop that maintains electron balance. The synergistic interactions between cerium and manganese enable rapid electron transfer between Ce4+ and Mn3+, facilitating the regeneration of Ce3+ and Mn4+. Due to the increase of the dual redox conjugate pairs and the surface reactive oxygen species, the catalytic ozonation activity and stability of Ce-Mn/Al2O3 was enhanced.

The role and possible mechanism of the ferroptosis-related SLC7A11/GSH/GPX4 pathway in myocardial ischemia-reperfusion injury.

BACKGROUND: Myocardial ischemia-reperfusion injury (MI/RI) is an unavoidable risk event for acute myocardial infarction, with ferroptosis showing close involvement. We investigated the mechanism of MI/RI inducing myocardial injury by inhibiting the ferroptosis-related SLC7A11/glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway and activating mitophagy. METHODS: A rat MI/RI model was established, with myocardial infarction area and injury assessed by TTC and H&E staining. Rat cardiomyocytes H9C2 were cultured in vitro, followed by hypoxia/reoxygenation (H/R) modeling and the ferroptosis inhibitor lipoxstatin-1 (Lip-1) treatment, or 3-Methyladenine or rapamycin treatment and overexpression plasmid (oe-SLC7A11) transfection during modeling. Cell viability and death were evaluated by CCK-8 and LDH assays. Mitochondrial morphology was observed by transmission electron microscopy. Mitochondrial membrane potential was detected by fluorescence dye JC-1. Levels of inflammatory factors, reactive oxygen species (ROS), Fe2+, malondialdehyde, lipid peroxidation, GPX4 enzyme activity, glutathione reductase, GSH and glutathione disulfide, and SLC7A11, GPX4, LC3II/I and p62 proteins were determined by ELISA kit, related indicator detection kits and Western blot. RESULTS: The ferroptosis-related SLC7A11/GSH/GPX4 pathway was repressed in MI/RI rat myocardial tissues, inducing myocardial injury. H/R affected GSH synthesis and inhibited GPX4 enzyme activity by down-regulating SLC7A11, thus promoting ferroptosis in cardiomyocytes, which was averted by Lip-1. SLC7A11 overexpression improved H/R-induced cardiomyocyte ferroptosis via the GSH/GPX4 pathway. H/R activated mitophagy in cardiomyocytes. Mitophagy inhibition reversed H/R-induced cellular ferroptosis. Mitophagy activation partially averted SLC7A11 overexpression-improved H/R-induced cardiomyocyte ferroptosis. H/R suppressed the ferroptosis-related SLC7A11/GSH/GPX4 pathway by inducing mitophagy, leading to cardiomyocyte injury. CONCLUSIONS: Increased ROS under H/R conditions triggered cardiomyocyte injury by inducing mitophagy to suppress the ferroptosis-related SLC7A11/GSH/GPX4 signaling pathway activation.

Parasitic Leiomyoma at Laparoscopic Trocar Site: A Report of 2 Cases.

BACKGROUND Parasitic leiomyoma refers to leiomyomas outside the uterus, with a prevalence of 0.07%. Patients are initially asymptomatic and may later develop abdominal pain and abdominal distension. Parasitic leiomyomas at a trocar site are extremely rare and lack detailed reporting. Here, we report 2 cases of parasitic leiomyoma at trocar sites. CASE REPORT Case 1. The patient was a 47-year-old woman with parasitic leiomyomas at a left trocar site 4 years after laparoscopic total hysterectomy. After being diagnosed with 3 masses on the surface of the sigmoid colon and 2 in the pelvic cavity, the patient underwent laparoscopic removal of a pelvic lesion and 3 lesions on the surface of the colon, combined with excision of abdominal wall masses. The pathology result indicated that the masses at the left trocar site were multiple leiomyomas, the intestinal mass was multiple leiomyomas with abundant cells, and the pelvic mass was fibrous capsule parietal tissue. This patient received 3 months of gonadotropin-releasing hormone agonist (GnRH-a) treatment, and was followed up for 9 months without recurrence. Case 2. The patient was a 50-year-old woman with parasitic leiomyoma at the right trocar site 15 years after laparoscopic removal of the right ovarian cyst. At admission, she underwent transabdominal total hysterectomy, bilateral fallopian tube resection, and abdominal wall lesion resection. The pathology report showed multiple leiomyomas of the uterus, and the cell-rich parasitic leiomyoma at right trocar site with unclear boundary. She received 3 months of GnRH-a treatment, and was followed up for 6 months without recurrence. CONCLUSIONS For patients with a history of laparoscopy, gynecologists should be alert to the occurrence of parasitic leiomyoma.

Effect of comorbid psychologic and somatic symptom trajectories on early onset substance use among U.S. youth in the ABCD study.

BACKGROUND: Adolescent substance use (SU) is often motivated by a desire to alleviate undesirable symptoms. To test the self-medication hypothesis, we examined associations between comorbid psychologic and somatic symptom trajectories across early adolescence and early onset SU. METHODS: Using Adolescent Brain Cognitive Development Study® data, we differentiated youth who reported no SU at baseline based on their comorbid anxiety, depression, pain, somatic and somnolence symptom trajectories. The outcome, early onset SU (by age 13-14 years) was derived from self-reported alcohol (≥full drink), tobacco (full regular/e-cigarette), marijuana, or other drug use over 5 years. RESULTS: 8311 participants were classified with Asymptomatic (27.8 %), Low/stable (39 %), Moderate/persistent (25.3 %) or High/worsening trajectories (7.9 %) from age 9.97 ± 0.74 to 13.57 ± 0.88 years. Early onset SU was 56 % higher for Moderate-High compared to Asymptomatic-Low symptom trajectory groups (12.5 % vs. 8.5 %; OR 1.56 [95 % CI 1.33, 1.79]). Adjusted for covariates, the High/worsening group was more likely than the Asymptomatic group to report use of any substance (adj.OR 2.13 [95 % CI 1.40, 3.25], Alcohol (adj.OR 2.80 [95 % CI 1.56, 5.02]), Tobacco (adj.OR 2.09 [95 % CI 1.23, 3.55]), and Marijuana (adj.OR 2.33 [95 % CI 1.36, 3.99]). Longitudinal, time-lagged analyses revealed potential feedback effects of earlier depression on subsequent SU, and earlier SU on later depression (p < 0.001). CONCLUSION: Higher comorbid symptom trajectories emerging in late childhood increased the likelihood of early onset SU. Since negative feedback loops may contribute to symptom persistency, ongoing and potentially harmful SU for at-risk youth, addressing comorbid symptoms that emerge during late childhood is warranted.

Longitudinal associations of e-cigarette use with cigarette, marijuana, and other drug use initiation among US adolescents and young adults: Findings from the population assessment of tobacco and health study (Waves 1-6).

INTRODUCTION: Research examining prospective links of e-cigarette use with cigarette, marijuana, and other substance use has been limited largely to 1-2-year follow-up periods and focused on younger adolescents. This study examined longitudinal associations of e-cigarette use with cigarette, marijuana, and other substance use initiation among U.S. adolescents and young adults (AYAs) across an eight-year period. METHODS: Adolescent (ages 12-17) and young adult (ages 18-25) data from waves 1-6 of the nationally representative Population Assessment of Tobacco and Health study (2013-2021) were used. Discrete time survival models with time-varying weights were employed to examine the risk of cigarette, marijuana, and other drug use initiation over an eight-year follow-up period among AYAs with no lifetime use of e-cigarettes/other tobacco, lifetime but no past 30-day use of e-cigarettes/other tobacco, past 30-day e-cigarettes only, other tobacco use only, or past 30-day e-cigarette/other tobacco use. We compare our time-varying weighting approach to a traditional time-invariant/complete case weighting approach. RESULTS: Across six follow-up waves, all three past 30-day nicotine/tobacco use groups, including e-cigarettes only, had greater risk for cigarette, marijuana, and other drug use initiation relative to those not using nicotine/tobacco. The three past 30-day nicotine/tobacco use groups did not differ from each other in risk for marijuana use initiation. Associations were smaller in magnitude for young adults compared to adolescents, but significant for both age groups. CONCLUSIONS: Substance use initiation risks persist beyond 1-2 years for U.S. AYAs using e-cigarettes. Prevention strategies to reduce AYA e-cigarette use are needed to reduce cancer-related risk.

The application value of 24†h Holter monitoring indices in predicting MACEs outside the hospital within three years after PCI in patients with STEMI.

Background: Evaluating cardiovascular risk in patients experiencing acute ST-elevation myocardial infarction (STEMI) and undergoing percutaneous coronary intervention (PCI) is crucial for early intervention and improving long-term outcomes. 24 h Holter monitoring provides continuous cardiac electrophysiological data, enabling the detection of arrhythmias and autonomic dysfunction that are not captured during routine examinations. This study aimed to examine the relationship between Holter monitoring metrics and the occurrence of out-of-hospital major adverse cardiovascular events (MACEs) following PCI in patients with STEMI, offering insights into cardiovascular risk evaluation. Methods: This prospective cohort study included STEMI patients undergoing PCI. 24 h Holter monitoring data were recorded, including heart rate, heart rate variability (HRV) metrics such as SDNN and SDANN index, heart rate deceleration capacity (DC) at different time scales (DC2, DC4, DC8), and the frequency of premature ventricular contractions (PVCs). Independent correlations between these indices and MACEs, as well as cardiovascular deaths, were investigated using multifactorial logistic regression. Predictive capacities were assessed through receiver operating characteristic (ROC) curves. Results: A total of 172 participants were enrolled in this study. Over the 3-year follow-up period, MACEs were observed in 57 patients, including 20 cases of cardiac death. In logistic regression models adjusted for confounding variables, SDNN [OR: 0.980; 95% CI: (0.967, 0.994); p = 0.005] and SDANN index [OR: 0.982; 95% CI: (0.969, 0.996); p = 0.009] were negatively associated with the incidence of MACEs. Conversely, the slowest heart rate [OR: 1.075; 95% CI: (1.022, 1.131); p = 0.005] and frequent PVCs [OR: 2.685; 95% CI: (1.204, 5.987); p = 0.016] demonstrated a positive association with MACEs. Furthermore, SDNN [OR: 0.957; 95% CI: (0.933, 0.981); p = 0.001], DC [OR: 0. 702; 95% CI: (0.526, 0.938); p = 0.017]) and DC4 [OR: 0.020; 95% CI: (0.001, 0.664); p = 0.029] were negatively associated with cardiac death. The ROC analysis results indicated that SDNN was an effective predictor of both MACEs [AUC: 0.688 (95% CI: 0.601-0.776)] and cardiac death [AUC: 0.752 (95% CI: 0.625-0.879)]. Conclusion: HRV, DC metrics, and frequent PVCs obtained by 24 h Holter monitoring were associated with the risk of MACEs in STEMI patients. These metrics can help clinicians identify at-risk patients early so that timely interventions.

CMOS-compatible reconstructive spectrometers with self-referencing integrated Fabry-Perot resonators.

Miniaturized reconstructive spectrometers play a pivotal role in on-chip and portable devices, offering high-resolution spectral measurement through precalibrated spectral responses and AI-driven reconstruction. However, two key challenges persist for practical applications: artificial intervention in algorithm parameters and compatibility with complementary metal-oxide-semiconductor (CMOS) manufacturing. We present a cutting-edge miniaturized reconstructive spectrometer that incorporates a self-adaptive algorithm referenced with Fabry-Perot resonators, delivering precise spectral tests across the visible range. The spectrometers are fabricated with CMOS technology at the wafer scale, achieving a resolution of ~2.5 nm, an average wavelength deviation of ~0.27 nm, and a resolution-to-bandwidth ratio of ~0.46%. Our approach provides a path toward versatile and robust reconstructive miniaturized spectrometers and facilitates their commercialization.

Reconfigurable memlogic long wave infrared sensing with superconductors.

Optical sensors with in-cell logic and memory capabilities offer new horizons in realizing machine vision beyond von Neumann architectures and have been attempted with two-dimensional materials, memristive oxides, phase-changing materials etc. Noting the unparalleled performance of superconductors with both quantum-limited optical sensitivities and ultra-wide spectrum coverage, here we report a superconducting memlogic long-wave infrared sensor based on the bistability in hysteretic superconductor-normal phase transition. Driven cooperatively by electrical and optical pulses, the device offers deterministic in-sensor switching between resistive and superconducting (hence dissipationless) states with persistence > 105 s. This results in a resilient reconfigurable memlogic system applicable for, e.g., encrypted communications. Besides, a high infrared sensitivity at 12.2 µm is achieved through its in-situ metamaterial perfect absorber design. Our work opens the avenue to realize all-in-one superconducting memlogic sensors, surpassing biological retina capabilities in both sensitivity and wavelength, and presents a groundbreaking opportunity to integrate visional perception capabilities into superconductor-based intelligent quantum machines.

Risk factors for methotrexate resistance in low-risk gestational trophoblastic neoplasia patients (FIGO score 0-4).

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

PIBF1 regulates multiple gene expression via impeding long-range chromatin interaction to drive the malignant transformation of HPV16 integration epithelial cells.

INTRODUCTION: Human papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. OBJECTIVES: We established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. METHODS: We designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. RESULTS: We successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. CONCLUSION: We highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis.

Applying Life History Theory to Understand Earlier Onset of Puberty: An Adolescent Brain Cognitive Development Cohort Analysis.

PURPOSE: Life history theory posits that multigenerational exposure to adversity and deprivation influences childhood growth and development, including pubertal maturation. We applied this ecological, evolutionary theory to examine the contributions of distal and proximal adversity on early puberty, a potentially important marker for population health. METHODS: Baseline data from 5,645 girls in the adolescent brain cognitive development study were included. Early puberty was defined as midlate/post pubertal development by age 9-11 years. The contributions of multigenerational Black/Indigenous (Black, Indigenous and People of Color [BIPOC]) or Hispanic identities, intergenerational mental health, economic deprivation, personal trauma exposure and mental health, and proximal biological factors of premature birth and body mass index on early puberty were examined with hierarchical modeling. RESULTS: 1,225 girls (21.7%) had early puberty. BIPOC/Hispanic identity, familial adversity, economic deprivation, personal trauma, depression, and a higher body mass index contributed significantly toward early puberty. The effect of multigenerational adversity remained significant across models, but the likelihood of early puberty decreased sequentially for BIPOC and Hispanic youth as proximal adversities were added (e.g., OR decreased from 2.93 to 2.38 for BIPOC youth), supporting a synergistic effect of layered adversity on early puberty. DISCUSSION: This analysis supports life history theory as a coherent framework to understand early puberty among girls. Findings suggest monitoring pubertal timing as a population health indictor, like birth weight, prematurity, or life expectancy. Addressing early puberty may require policy and social changes to mitigate the negative impact of multiple layers of adversity including racial/ethnic disadvantage, family, and individual mental health and trauma, as well as economic insecurity.

One-step rolling fabrication of VO2 tubular bolometers with polarization-sensitive and omnidirectional detection.

Uncooled infrared detection based on vanadium dioxide (VO2) radiometer is highly demanded in temperature monitoring and security protection. The key to its breakthrough is to fabricate bolometer arrays with great absorbance and excellent thermal insulation using a straightforward procedure. Here, we show a tubular bolometer by one-step rolling VO2 nanomembranes with enhanced infrared detection. The tubular geometry enhances the thermal insulation, light absorption, and temperature sensitivity of freestanding VO2 nanomembranes. This tubular VO2 bolometer exhibits a detectivity of ~2 × 108 cm Hz1/2 W-1 in the ultrabroad infrared spectrum, a response time of ~2.0 ms, and a calculated noise-equivalent temperature difference of 64.5 mK. Furthermore, our device presents a workable structural paradigm for polarization-sensitive and omnidirectional light coupling bolometers. The demonstrated overall characteristics suggest that tubular bolometers have the potential to narrow performance and cost gap between photon detectors and thermal detectors with low cost and broad applications.

Development of On-DNA Cyclic Imide Synthesis for DNA Encoded Library Construction.

Here, we describe a novel method for the on-DNA synthesis of cyclic imides, an important class of molecules that includes several well-known medications. Significantly, the new method enabled on-DNA synthesis under mild conditions with high conversions and a broad functional group tolerance, utilizing ubiquitous bifunctional amines and bis-carboxylic acid, or alkyl halides, and therefore served as the linchpin for DNA encoded library (DEL) synthesis. The mechanism study of off-DNA and on-DNA chemical transformations revealed unique insights in contrast to conventional chemical transformation.

Associations of Co-occurring Symptom Trajectories With Sex, Race, Ethnicity, and Health Care Utilization in Children.

Importance: Co-occurring physical and psychological symptoms during childhood and early adolescence may increase risk of symptom persistence into adulthood. Objective: To describe co-occurring pain, psychological, and sleep disturbance symptom (pain-PSS) trajectories in a diverse cohort of children and the association of symptom trajectory with health care utilization. Design, Setting, and Participants: This cohort study was a secondary analysis of longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study, collected between 2016 and 2022 at 21 research sites across the US. Participants included children with 2 to 4 complete annual symptom assessments. Data were analyzed from November 2022 to March 2023. Main Outcomes and Measures: Four-year symptom trajectories were derived from multivariate latent growth curve analyses. Pain-PSS scores, including depression and anxiety, were measured using subscales from the Child Behavior Checklist and the Sleep Disturbance Scale of Childhood. Nonroutine medical care and mental health care utilization were measured using medical history and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) items. Results: A total of 11 473 children (6018 [52.5%] male; mean [SD] age at baseline, 9.91 [0.63] years) were included in analyses. Four no pain-PSS and 5 pain-PSS trajectories were supported with good or excellent model fit (predicted probabilities, 0.87-0.96). Most children (9327 [81.3%]) had asymptomatic or low, intermittent, or single symptom trajectories. Approximately 1 in 5 children (2146 [18.7%]) had moderate to high co-occurring symptom trajectories that persisted or worsened. Compared with White children, there was a lower relative risk of having moderate to high co-occurring symptom trajectories among Black children (adjusted relative risk ratio [aRRR] range, 0.15-0.38), Hispanic children (aRRR range, 0.58-0.67), and children who identified as another race (including American Indian, Asian, Native Hawaiian, and other Pacific Islader; aRRR range, 0.43-0.59). Less than half of children with moderate to high co-occurring symptom trajectories used nonroutine health care, despite higher utilization compared with asymptomatic children (nonroutine medical care: adjusted odds ratio [aOR], 2.43 [95% CI, 1.97-2.99]; mental health services: aOR, 26.84 [95% CI, 17.89-40.29]). Black children were less likely to report nonroutine medical care (aOR, 0.61 [95% CI, 0.52-0.71]) or mental health care (aOR, 0.68 [95% CI, 0.54-0.87]) than White children, while Hispanic children were less likely to have used mental health care (aOR, 0.59 [95% CI, 0.47-0.73]) than non-Hispanic children. Lower household income was associated with lower odds of nonroutine medical care (aOR, 0.87 [95% CI, 0.77-0.99]) but not mental health care. Conclusions and Relevance: These findings suggest there is a need for innovative and equitable intervention approaches to decrease the potential for symptom persistence during adolescence.

Associations Between Vascular Risk Factor Levels and Cognitive Decline Among Stroke Survivors.

Importance: Incident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain. Objective: To evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline. Design, Setting, and Participants: Individual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023. Exposures: Time-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels. Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results: A total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (-0.04 points/y faster per each 10-mg/dL increase [95% CI, -0.08 to -0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (-0.05 points/y faster per 10-mg/dL increase [95% CI, -0.09 to -0.01 points/y]; P = .01; -0.07 points/y faster per 10-mg/dL increase [95% CI, -0.11 to -0.03 points/y]; P = .002) but not executive function or memory declines. Conclusions and Relevance: In this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline.

Targeting PARP for the optimal immunotherapy efficiency in gynecologic malignancies.

Gynecologic cancer, which includes ovarian, cervical, endometrial, vulvar, and vaginal cancer, is a major health concern for women all over the world. Despite the availability of various treatment options, many patients eventually progress to advanced stages and face high mortality rates. PARPi (poly (ADP-ribose) polymerase inhibitor) and immune checkpoint inhibitor (ICI) have both shown significant efficacy in the treatment of advanced and metastatic gynecologic cancer. However, both treatments have limitations, including inevitable resistance and a narrow therapeutic window, making PARPi and ICI combination therapy a promising approach to treating gynecologic malignancies. Preclinical and clinical trials have looked into the combination therapy of PARPi and ICI. PARPi improves ICI efficacy by inducing DNA damage and increasing tumor immunogenicity, resulting in a stronger immune response against cancer cells. ICI, conversly, can increase PARPi sensitivity by priming and activating immune cells, consequently prompting immune cytotoxic effect. Several clinical trials in gynecologic cancer patients have investigated the combination therapy of PARPi and ICI. When compared to monotherapy, the combination of PARPi and ICI increased progression-free survival and overall survival in ovarian cancer patients. The combination therapy has also been studied in other types of gynecologic cancer, including endometrial and cervical cancer, with promising results. Finally, the combination therapeutic strategy of PARPi and ICI is a promising approach in the treatment of gynecologic cancer, particularly advanced and metastatic stages. Preclinical studies and clinical trials have demonstrated the safety and efficacy of this combination therapy in improving patient outcomes and quality of life.

EREG is a risk factor for the prognosis of patients with cervical cancer.

Background: Cervical cancer continues to threaten women's health worldwide. Identifying critical oncogenic molecules is important to drug development and prognosis prediction for patients with cervical cancer. Recent studies have demonstrated that epiregulin (EREG) is upregulated in various cancer types, which contributes to cancer progression by triggering the EGFR signaling pathway. However, the role of EREG is still unclear. Methods: In this study, we first conducted a comprehensive biological analysis to investigate the expression of EREG in cervical cancer. Then, we investigated the correlations between EREG expression level and clinicopathological features. In addition, we validated the effects of EREG expression on the proliferation and apoptosis of cervical cancer cells. Results: Based on the public database, we found that the expression of EREG was higher in advanced cervical cancer samples. Survival analysis showed that EREG was a risk factor for the prognosis of cervical cancer. In vitro experiments demonstrated that EREG knockdown undermined proliferation and promoted apoptosis in cancer cells. Conclusion: EREG plays a vital role in the progression of cervical cancer, which contributes to hyperactive cell proliferation and decreased cell apoptosis. It might be a valuable target for prognosis prediction and drug development for cervical cancer in the future.

Reaching Populations to Address Disparities in Cancer Care Delivery: Results From a Six-Site Initiative.

BACKGROUND: Large segments of the US population do not receive quality cancer care due to pervasive and systemic inequities, which can increase morbidity and mortality. Multicomponent, multilevel interventions can address inequities and improve care, but only if they reach communities with suboptimal access. Intervention studies often underenroll individuals from historically excluded groups. METHODS: The Alliance to Advance Patient-Centered Cancer Care includes 6 grantees across the United States who implemented unique multicomponent, multilevel intervention programs with common goals of reducing disparities, increasing engagement, and improving the quality of care for targeted populations. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework informed the evaluation efforts across sites. Each Alliance site identified their intended populations, which included underrepresented minorities (eg, Black and Latinx persons), individuals who prefer a language other than English, and rural residents. We evaluated the demographic characteristics of participants to determine program reach. RESULTS: Between 2018 and 2020, a total of 2,390 of 5,309 potentially eligible participants were enrolled across the 6 sites. The proportion of enrolled individuals with selected characteristics included 38% (n=908) Black adults, 24% (n=574) Latinx adults, 19% (n=454) preferring a language other than English, and 30% (n=717) rural residents. The proportion of those enrolled who were the intended population was commensurate to the proportion with desired characteristics in those identified as potentially eligible. CONCLUSIONS: The grantees met or exceeded enrollments from their intended populations who have been underserved by quality cancer care into patient-centered intervention programs. Intentional application of recruitment/engagement strategies is needed to reach individuals from historically underserved communities.

Dual color infrared photodetector with superconducting metamaterials.

Superconducting photodetection offers a wide spectral coverage ranging from the microwave to X-ray, and in the short wavelength range, single photon sensitivity can be achieved. However, in the longer wavelength infrared region, the system detection efficiency is low due to the lower internal quantum efficiency and weak optical absorption. Here, we utilized the superconducting metamatieral to enhance the light coupling efficiency and reach nearly perfect absorption at dual color infrared wavelengths. Dual color resonances arise from hybridization of local surface plasmon mode of the metamaterial structure and the Fabry-Perot-like cavity mode of metal (Nb)-dielectric (Si)-metamatieral (NbN) tri-layer structure. We demonstrated that, at the working temperature of 8 K slightly below TC ∼8.8 K, this infrared detector exhibits the peak responsivity of 1.2 × 106V/W and 3.2 × 106V/W at two resonant frequencies 36.6 THz and 104 THz, respectively. The peak responsivity is enhanced about ∼8 and ∼22 times, respectively, compared to that of non-resonant frequency (67 THz). Our work provides a way to harvest infrared light efficiently and hence improve the sensitivity of superconducting photodetectors in multispectral infrared range, which may find promising applications in thermal image and gas sensing etc.

Preparation of Heavy Metal Trapping Flocculant Polyacrylamide-Glutathione and Its Application for Cadmium Removal from Water.

In this study, a heavy metal trapping gel with multiple ligand groups was prepared for the first time using response surface methodology. The gel was produced by condensing and grafting glutathione as a grafting monomer onto the main polyacrylamide chain, based on the Mannich reaction mechanism with formaldehyde. FTIR, SEM, TG-DSC, and zeta potentials were used to characterize the gel. The results demonstrated that the gel was morphologically folded and porous, with a net-like structure, which enhanced its net trapping and sweeping abilities, and that glutathione was used to provide sulfhydryl groups to boost the metal trapping ability of polyacrylamide. Coagulation experiments showed that the highest efficiency of the removal of Cd ions from water samples was achieved when the concentration of polyacrylamide-glutathione was 84.48 mgL-1, the concentration of Cd was 10.0 mgL-1, the initial turbidity was 10.40 NTU, and the initial pH was 9.0. Furthermore, the presence of two cations, Cu and Zn, had an inhibitory effect on the removal of Cd ions. In addition, analysis of the zeta potential revealed the flocculation of polyacrylamide-glutathione. The flocculation mechanism of glutathione is mainly chelation, adsorption bridging, and netting sweeping.