Volume replacement in tumor plastic surgery and breast-conserving surgery using 3D grid and strip­shaped acellular dermal matrix: Two case reports.

The present study was driven by the scarcity of suitable materials for mending partial breast defects and the imperative considerations of safety and durability. The current study presents findings from two female patients, aged 59 and 40, who underwent breast cancer treatment. Patient 1 underwent a mastectomy with a sentinel lymph node biopsy, while patient 2 underwent a partial mastectomy with axillary lymph node dissection. Core needle biopsy confirmed invasive ductal carcinoma in both cases. Breast ultrasound revealed hypoechoic lesions with smooth edges. The reconstruction of the breast defect employed an acellular dermal matrix, and the safety and cosmetic outcomes for each patient were analyzed. At 3 months post-radiotherapy, neither patient experienced significant complications. The preservation of breast contour and volume was satisfactory, with no postoperative tumor recurrences detected. In summary, utilizing an acellular dermal matrix with a three-dimensional grid design for partial breast defect reconstruction offers a viable alternative that aligns with oncological safety standards and provides good cosmetic results.

Shearo-caloric effect enhances elastocaloric responses in polymer composites for solid-state cooling.

Room-temperature elastocaloric cooling is considered as a zero-global-warming-potential alternative to conventional vapor-compression refrigeration technology. However, the limited entropy and large-deformation features of elastocaloric polymers hinder the creation of the breakthrough in their caloric responses and device development. Herein, we report that the addition of a small amount of inorganic nanofillers into the polymer induces the aggregate of the effective elastic chains via shearing the interlaminar molecular chains, which provides an additional contribution to the entropy in elastocaloric polymers. Consequently, the adiabatic temperature change of -18.0 K and the isothermal entropy change of 187.4 J kg-1 K-1 achieved in the polymer nanocomposites outperform those of current elastocaloric polymers. Moreover, a large-deformation cooling system with a work recovery efficiency of 56.3% is demonstrated. This work opens a new avenue for the development of high-performance elastocaloric polymers and prototypes for solid-state cooling applications.

The Intermode Polariton Parametric Scattering Laser in a Strong Coupled Microcavity Via Two-Photon Absorption.

Exciton-polaritons, hybrid quasiparticles from the strong coupling of excitons and cavity photons in semiconductor microcavities, offer a platform for exploring quantum coherence and nonlinear optical properties. The unique polariton parametric scattering (PPS) laser is of interest for its potential in quantum technologies and nonlinear devices. However, direct resonant excitation of polaritons in strong-coupling microcavities is challenging. This study proposes an innovative two-photon absorption (TPA) pump mechanism to address this. We observe TPA-driven PPS lasing in a strongly coupled microcavity at room temperature. High K-value exciton injections promote coherent stimulated emission of polariton scattering through intermode channels. Angle-resolved spectra confirm a TPA process, showing evolution from pump-state to signal-state. Hanbury Brown-Twiss measurement of second-order correlation g2(τ) of signal state indicates a phase transition from a classical thermal state to a quantum coherent state. Theoretical modeling provides insights into the physical mechanisms of PPS. Our work advances nonlinear phenomena exploration in strongly coupled light-matter systems, contributing to quantum polaritonics and nonlinear optics.

Cross-cultural adaptation and validation of the caregiver self-efficacy in contributing to patient self-care scale in China.

BACKGROUND: Caregiver self-efficacy is crucial in improving patient outcomes and caregiver well-being, but there is a lack of suitable scales to assess this concept within the context of Chinese culture. This study aimed to cross-culturally translate the Caregiver Self-Efficacy in Contributing to Patient Self-Care (CSE-CSC) Scale and evaluate its psychometric properties using classical test theory and item response theory. METHODS: The CSE-CSC scale was adapted using Brislin's translation model after obtaining authorization from the original author. A multicenter, cross-sectional study was conducted to assess the psychometric properties of this scale. Classical test theory was used to evaluate reliability (internal consistency, test-retest reliability), validity (content validity, structural validity, convergent validity), and floor and ceiling effects. Item response theory was employed to assess the fit of the rating scale model, reliability, item difficulties, and measurement invariance. RESULTS: The translation and cultural adaptation process was completed. Classical test theory demonstrated good internal consistency (Cronbach's α = 0.935) and test-retest reliability (ICC from 0.784 to 0.829, p<0.001). The I-CVI and K* of each item ranged from 0.875 to 1.00 and 0.871 to 1.00. The first-order 2-factor model fit well (χ2/df = 3.71, RMSEA = 0.082, SRMR = 0.032, CFI = 0.973, TLI = 0.60). Convergent validity showed that the CSE-CSC scores had a strong positive correlation with three separate scales of the CC-SC-CII. There was no floor and ceiling effect in this scale. Rasch analysis showed that the CSE-CSC scale demonstrated a good fit to the rating scale model and exhibited excellent reliability (person/item separation index>2, person/item reliability coefficients>0.8). The Wright map showed that item difficulty matched the respondents' measured abilities. The analysis of differential item functioning (DIF) showed that all items were comparable in gender. CONCLUSIONS: This study indicated that the CSE-CSC scale had good reliability, validity, difficulty degree, and measurement invariance. The CSE-CSC scale can be used to measure caregiver self-efficacy of Chinese patients with multiple chronic conditions.

Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-ß production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.

An overview of influenza A virus detection methods: from state-of-the-art of laboratories to point-of-care strategies.

Influenza A virus (IAV), a common respiratory infectious pathogen, poses a significant risk to personal health and public health safety due to rapid mutation and wide host range. To better prevent and treat IAV, comprehensive measures are needed for early and rapid screening and detection of IAV. Although traditional laboratory-based techniques are accurate, they are often time-consuming and not always feasible in emergency or resource-limited areas. In contrast, emerging point-of-care strategies provide faster results but may compromise sensitivity and specificity. Here, this review critically evaluates various detection methods for IAV from established laboratory-based procedures to innovative rapid diagnosis. By analyzing the recent research progress, we aim to address significant gaps in understanding the effectiveness, practicality, and applicability of these methods in different scenarios, which could provide information for healthcare strategies, guide public health response measures, and ultimately strengthen patient care in the face of the ongoing threat of IAV. Through a detailed comparison of diagnostic models, this review can provide a reliable reference for rapid, accurate and efficient detection of IAV, and to contribute to the diagnosis, treatment, prevention, and control of IAV.

Environmental Toxicant Exposure and Depressive Symptoms.

Importance: Recognizing associations between exposure to common environmental toxicants and mental disorders such as depression is crucial for guiding targeted mechanism research and the initiation of disease prevention efforts. Objectives: To comprehensively screen and assess the associations between potential environmental toxicants and depressive symptoms and to assess whether systemic inflammation serves as a mediator. Design, Setting, and Participants: A total of 3427 participants from the 2013-2014 and 2015-2016 waves of the National Health and Nutrition Examination and Survey who had information on blood or urine concentrations of environmental toxicants and depression scores assessed by the 9-item Patient Health Questionnaire (PHQ-9) were included. Statistical analysis was performed from July 1, 2023, to January 31, 2024. Exposures: Sixty-two toxicants in 10 categories included acrylamide, arsenic, ethylene oxide, formaldehyde, iodine, metals, nicotine metabolites, polycyclic aromatic hydrocarbons, volatile organic compound (VOC) metabolites; and perchlorate, nitrate, and thiocyanate. Main Outcomes and Measures: An exposome-wide association study and the deletion-substitution-addition algorithm were used to assess associations with depression scores (PHQ-9 ≥5) adjusted for other important covariates. A mediation analysis framework was used to evaluate the mediating role of systemic inflammation assessed by the peripheral white blood cell count. Results: Among the 3427 adults included, 1735 (50.6%) were women, 2683 (78.3%) were younger than 65 years, and 744 (21.7%) were 65 years or older, with 839 (24.5%) having depressive symptoms. In terms of race and ethnicity, 570 participants (16.6%) were Mexican American, 679 (19.8%) were non-Hispanic Black, and 1314 (38.3%) were non-Hispanic White. We identified associations between 27 chemical compounds or metals in 6 of 10 categories of environmental toxicants and the prevalence of depressive symptoms, including the VOC metabolites N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (odds ratio [OR], 1.74 [95% CI, 1.38, 2.18]) and total nicotine equivalent-2 (OR, 1.42 [95% CI, 1.26-1.59]). Men and younger individuals appear more vulnerable to environmental toxicants than women and older individuals. Peripheral white blood cell count mediated 5% to 19% of the associations. Conclusions and Relevance: In this representative cross-sectional study of adults with environmental toxicant exposures, 6 categories of environmental toxicants were associated with depressive symptoms with mediation by systemic inflammation. This research provides insight into selecting environmental targets for mechanistic research into the causes of depression and facilitating efforts to reduce environmental exposures.

Clinical analysis of lupus miliaris disseminatus faciei: a cross-sectional study and literature review.

Background: The clinical similarity of lupus miliaris disseminatus faciei (LMDF) and other papular granulomatous facial disorders often makes its correct diagnosis challenging. Diagnosis often requires the assistance of pathological examination, and dermoscopy can be used as an auxiliary and non-invasive examination method, however, the current findings remain incomplete. Objectives: This study aimed to summarize the clinical, histopathological and dermoscopic features of LMDF in the Chinese Han population and aiming to provide practical significance to correct diagnosis. Methods: 109 patients of LMDF were collected in the Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University from August 2015 to August 2023. The clinical and histopathological manifestations of all patients, as well as the dermoscopic image features of 44 cases, including background, follicular findings, vessels, and other structures, were summarized and evaluated. Results: The most significant histopathological features of LMDF in 109 cases is epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. The most significant dermoscopic features of LMDF in all 44 cases were orange structureless background (30/44), follicular plug (32/44), follicular white scar-like area (32/44), unspecific linear vessels (24/44), linear vessels with branch (24/44) and white streaks (18/44). Conclusion: Histopathologically, LMDF is characterized by the presence of epithelioid granulomatous infiltrate in the superficial dermis, with or without caseation. Dermoscopically, it exhibits a distinctive orange structureless background, follicular plug, follicular white scar-like area, nonspecific linear vessels, linear vessels with branches, and white streaks.

Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH).

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

A self-catalyzing strategy for co-immobilization of two distinct proteins at equimolar ratio: A case study of 3A and 2C to develop a chromatographic method for finding prospective dual-target compoundsfrom complex matrices.

BACKGROUND: Immobilized proteins hold promise as the basic units that have enabled a broad range of analytical applications within chemical measurement science. As yet, the co-immobilization of diverse proteins at precise ratio and whether they give rise to improved analytical performance remain challengeable. Herein, we utilized a circularly permuted HaloTag (cpHaloTag) to achieve the co-immobilization of two proteins at precise ratio, which was applied in developing a chromatographic method with improved specificity for pursuing dual-target compounds. RESULTS: The methodology involved the fusion 3A and 2C at N- and C-terminuses of cpHaloTag, the immobilization of the fusion protein onto silica gel through bioorthogonal reaction, the morphological and functional characterization, the application in finding dual-target compounds. Expression of the fusion protein in E. coli system showed a yield of milligram level with the presence of 3A and 2C domains. Immobilization of the protein was achieved in 10 min with a reaction efficiency more than 88.5 %. Immobilized 3A-cpHalo-2C exhibited higher specificity and better retentions of canonical compounds of the two enzymes in comparison with the column containing immobilized 3A or 2C alone. In real sample application, screening analysis found that hyperoside, cymaroside, and baicalin were dual-target compounds in concert with 3A and 2C in Shuanghuanglian extract. SIGNIFICANCE: Taking 3A and 2C as probe, we proposed a simple method for direct co-immobilization of diverse proteins from cell lysates and demonstrated an affinity chromatographic-based dual-target compound screening platform. The implications of these methodology are possible to insight the de novo design of multi-target surface for fabricating new bioanalytical methods with improved performance.

Kolmogorov-Zurbenko filter coupled with machine learning to reveal multiple drivers of surface ozone pollution in China from 2015 to 2022.

Near-surface ozone pollution is a significant concern in China. Its meteorological drivers are uncontrolled, stressing an urgent need to quantify the anthropogenic-driven components. This study employs explainable machine learning (ML) algorithms to predict ozone concentrations, emphasizing the anthropogenic-driven trends after accounting for meteorological effects. Results present that radiation is the most important meteorological factor affecting ozone pollution in the Yangtze River Delta (YRD), Pearl River Delta (PRD), and Sichuan Basin (SCB), while temperature is dominant for the North China Plain (NCP). Even at lower temperatures, stronger solar radiation can still lead to the accumulation of higher ozone concentrations. The anthropogenic-driven ozone concentration showed an upward trend in China, with an interannual growth rate of 2.61 µg/m3 a-1 from 2015 to 2022. Nonetheless, its rising trend experienced a post-2019 downturn, due to the COVID-19 lockdown and emission reduction strategies. It started to rise in 2022. Regionally, NCP has the highest ozone concentration, the SCB has the most pronounced increase in 2022, but the PRD has no noticeable variation and no significant seasonal change after 2019. As for precursor emissions, the urban areas in China are mostly located in the VOC-limited (volatile organic component) and transitional regimes, highlighting that VOC control is more cost-effective.

Dose-Response Relationship Between Perceived Control and Depression in Patients With Chronic Heart Failure: A Multicenter and Cross-sectional Study.

BACKGROUND: Little is known regarding the relationship between perceived control and depression in patients with chronic heart failure (CHF), particularly in terms of their dose-response relationship. OBJECTIVE: The aim of this study was to explore this relationship based on linear and nonlinear hypotheses and potential subgroup differences in patients with CHF. METHODS: A total of 308 patients with CHF were included in the study. Data on perceived control, depression, and relevant covariates, such as gender, age, New York Heart Association classification, and comorbidity burden, were collected. Logistic regression, Spearman correlation, and restricted cubic spline analysis were used for data analysis. RESULTS: Compared with the patients in the first quartiles of perceived control scores (0-16), those in the other 3 quartiles had a lower risk of depression (odds ratios of 0.29, 0.21, and 0.20, respectively; P < .05). Furthermore, a negative correlation between perceived control and depression (r = -0.317, P < .01) was observed. The restricted cubic spline analysis revealed an "L-shaped" curve relationship between perceived control and the presence of depression (P for nonlinear < .01). Compared with patients with a perceived control within the 5th percentile (10 scores), as the perceived control increased, the risk of depression rapidly decreased from "1" until it reached a threshold (20 scores) and stabilized. This trend remained consistent across the subgroups grouped by gender, age, New York Heart Association classification, and comorbidity burden. CONCLUSIONS: Interventions targeting perceived control may hold valuable implications for reducing the risk of depression in patients with CHF, particularly those who have not yet reached the threshold.

Lead specifically declines tyrosine hydroxylase activity to induce the onset of Parkinson's disease through disrupting dopamine biosynthesis in fly models.

Parkinson's disease (PD) is one of the fastest-growing neurodegenerative diseases and has been linked to the exposure to numerous environmental neurotoxins. Although lead (Pb) exposure has been related to the development of PD, the molecular target of Pb to cause the onset of PD is insufficiently investigated. Herein, we explored the effects of Pb exposure on behavior, pathophysiology, and gene expression of wild-type (WT) fly (Drosophila melanogaster) by comparison with its PD model. After exposure to Pb, the WT flies showed PD-like locomotor impairments and selective loss of dopaminergic (DAergic) neurons, displaying similar phenotypes to fly PD model (PINK1). Transcriptomic analysis showed the similarity in gene expression profiles between Pb treatment WT flies and PINK1 mutant flies. Moreover, Pb exposure resulted in endogenous dopamine deficits in WT flies. Analyses of gene expression and enzyme activity confirmed that Pb exposure reduced tyrosine hydroxylase (TH) activity and led to failure of dopamine synthesis. Furthermore, molecular dynamics simulation confirmed that Pb was adsorbed by TH and subsequently inhibited the enzymatic activity. Exogenous injection of L-dopa and melatonin could partially rescue the pathological phenotypes of Pb-exposed flies and PD fly model. Antagonist injection of microRNA-133, which negatively regulated the expression of TH gene, ultimately rescued in the manifestation of PD phenotypes in flies. Involvement of TH overexpression mutants of fly strongly promoted the resistance to Pb exposure and rescued both behavior and the number of DAergic neurons. Therefore, our study elucidates the Pb molecular target in dopamine pathway and mechanism underlying the risks of Pb exposure on the occurrence of PD at environmentally-relevant concentrations.

AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study).

BACKGROUND: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. METHODS: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. FINDINGS: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P=0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. INTERPRETATION: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients' increased self-awareness.

A Novel Multi-modal Population-graph based Framework for Patients of Esophageal Squamous Cell Cancer Prognostic Risk Prediction.

Prognostic risk prediction is pivotal for clinicians to appraise the patient's esophageal squamous cell cancer (ESCC) progression status precisely and tailor individualized therapy treatment plans. Currently, CT-based multi-modal prognostic risk prediction methods have gradually attracted the attention of researchers for their universality, which is also able to be applied in scenarios of preoperative prognostic risk assessment in the early stages of cancer. However, much of the current work focuses only on CT images of the primary tumor, ignoring the important role that CT images of lymph nodes play in prognostic risk prediction. Additionally, it is important to consider and explore the inter-patient feature similarity in prognosis when developing models. To solve these problems, we proposed a novel multi-modal population-graph based framework leveraging CT images including primary tumor and lymph nodes combined with clinical, hematology, and radiomics data for ESCC prognostic risk prediction. A patient population graph was constructed to excavate the homogeneity and heterogeneity of inter-patient feature embedding. Moreover, a novel node-level multi-task joint loss was proposed for graph model optimization through a supervised-based task and an unsupervised-based task. Sufficient experimental results show that our model achieved state-of-the-art performance compared with other baseline models as well as the gold standard on discriminative ability, risk stratification, and clinical utility. The core code is available at https://github.com/wuchengyu123/MPGSurv.

Association between Volatile Organic Compound Exposure and Sex Hormones in Adolescents: The Mediating Role of Serum Albumin.

The associations between VOCs and sex hormones in adolescents remain unclear, and the role of serum albumin in these associations deserves to be explored. We conducted cross-sectional analyses using generalized linear models (GLMs), weighted quantile sum (WQS) regression, and mediation analysis, based on data from 584 adolescents from the National Health and Nutrition Examination Survey (NHANES). The GLM analyses revealed that seven kinds of mVOCs potentially affected sex hormone levels. According to the WQS regression results, 2-aminothiazoline-4-carboxylic acid (ATCA) was the major contributor to the significant associations of mixed mVOC exposure with testosterone, estradiol, and free androgen index in males; N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) was the major contributor to the significant associations of mixed mVOC exposure with sex hormone-binding globulin in males; and N-acetyl-S-(benzyl)-L-cysteine (BMA) was the major contributor to the significant associations of mixed mVOC exposure with the ratio of testosterone to estradiol in females. Moreover, serum albumin could mediate up to 9.2% of the associations between mixed exposure to mVOCs and sex hormones. Our findings could provide a reference for studies on the mechanisms underlying the effects of VOCs on sex hormones in adolescents and emphasize the necessity of reducing exposure to ATCA, AMCC, BMA, and their parent compounds.

Gamma-Tocotrienol Inhibits Proliferation and Growth of HSD17B4-Overexpressing HepG2 Liver Cancer Cells.

INTRODUCTION: Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the progression of hepatocellular carcinoma (HCC). AIMS: This study aimed to investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on the proliferation and growth of HSD17B4-overexpressing HepG2 cells. METHODS: HepG2 cells were transfected with empty or HSD17B4-overexpressing plasmids, followed by vitamin E (VE) or γ-T3 treatment. MTS assay, Western blotting, qRT-PCR, and flow cytometry were employed to assess cell proliferation, protein expression, mRNA levels, and apoptosis. HSD17B4 interaction with γ-T3 was assessed by quantifying γ-T3 in the collected precipitate of HSD17B4 using anti-flag magnetic beads. Tumor xenografts were established in NSG mice, and tumor growth was monitored. RESULTS: HSD17B4 overexpression significantly promoted HepG2 cell proliferation, which was effectively counteracted by VE or γ-T3 treatment in a dose-dependent manner. VE and γ-T3 did not exert their effects through direct regulation of HSD17B4 expression. Instead, γ-T3 was found to interact with HSD17B4, inhibiting its activity in catalyzing the conversion of estradiol (E2) into estrone. Moreover, γ-T3 treatment led to a reduction in cyclin D1 expression and suppressed key proliferation signaling pathways, such as ERK, MEK, AKT, and STAT3. Additionally, γ-T3 promoted apoptosis in HSD17B4-overexpressing HepG2 cells. In an in vivo model, γ-T3 effectively reduced the growth of HepG2 xenograft tumors. CONCLUSION: In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated pathways to inhibit tumor growth and enhance apoptosis.

Excess deaths and loss of life expectancy attributed to long-term NO2 exposure in the Chinese elderly.

BACKGROUND: Evidence linking nitrogen dioxide (NO2) air pollution to life span of high-vulnerability older adults is extensively scarce in low- and middle-income countries. This study seeks to quantify mortality risk, excess deaths, and loss of life expectancy (LLE) associated with long-term exposure to NO2 among elderly individuals in China. METHODS: A nationwide dynamic cohort of 20352 respondents ≥65 years old were enrolled from the China Longitudinal Health and Longevity Survey during 2005-2018. Residential exposures to NO2 and co-pollutants were assessed by well-validated spatiotemporal prediction models. A Cox regression model with time-dependent covariates was utilized to quantify the association of all-cause mortality with NO2 exposure, controlling for confounders such as demographics, lifestyle, health status, and ambient temperature. NO2-attributable deaths and LLE were evaluated for the years 2010 and 2020 based on the pooled NO2-mortality relation derived from multi-national cohort investigations. Decomposition analyses were conducted to dissociate net shift in NO2-related deaths between 2010 and 2020 into four primary contributing factors. RESULTS: A total of 14313 deaths were recorded during follow-up of approximately 100 hundred person-years (median 3.6 years). We observed an approximately linear relationship (nonlinear P = 0.882) of NO2 exposure with all-cause death across a broad range from 6.6 to 95.7 µg/m3. Every 10-µg/m3 rise in yearly average NO2 concentration was linked to a hazard ratio (HR) of 1.045 (95% confidence interval [CI]: 1.031-1.059). In the updated meta-analysis of this study and 9 existing cohorts, we estimated a pooled HR of 1.043 (95% CI: 1.023-1.063) for each 10-µg/m3 growth in NO2. Reaching a 10-µg/m3 counterfactual target of NO2 concentration in China could avoid 0.33 (95% empirical CI: 0.19-0.49) million premature deaths and an LLE of 0.40 (95% empirical CI: 0.23-0.59) years in 2010, which greatly dropped to 0.24 (95% empirical CI: 0.14-0.36) million deaths and 0.21 (95% empirical CI: 0.12-0.31) years of LLE in 2020. The net fall in NO2-attributable deaths (-26.8%) between 2010 and 2020 was primarily driven by the declines in both NO2 concentration (-41.6%) and mortality rate (-27.1%) under population growth (+41.0%) and age structure transition (+0.9%). CONCLUSIONS: Our findings provide national evidence for increased risk of premature death and loss of life expectancy attributed to later-life NO2 exposure among the elderly in China. In an accelerated aging society, strengthened clean air actions should be formulated to minimize the health burden and regional inequality in NO2-attributable mortality.