Abnormal Serum BDNF and p-mTOR in MDD in Adolescents with Childhood Trauma.

Background: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma. Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children's Depression Inventory (CDI) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control. Results: The serum levels of BDNF were significantly lower (p<0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p<0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=-0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value. Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.

GNAS knockout potentiates HDAC3 inhibition through viral mimicry-related interferon responses in lymphoma.

Despite selective HDAC3 inhibition showing promise in a subset of lymphomas with CREBBP mutations, wild-type tumors generally exhibit resistance. Here, using unbiased genome-wide CRISPR screening, we identify GNAS knockout (KO) as a sensitizer of resistant lymphoma cells to HDAC3 inhibition. Mechanistically, GNAS KO-induced sensitization is independent of the canonical G-protein activities but unexpectedly mediated by viral mimicry-related interferon (IFN) responses, characterized by TBK1 and IRF3 activation, double-stranded RNA formation, and transposable element (TE) expression. GNAS KO additionally synergizes with HDAC3 inhibition to enhance CD8+ T cell-induced cytotoxicity. Moreover, we observe in human lymphoma patients that low GNAS expression is associated with high baseline TE expression and upregulated IFN signaling and shares common disrupted biological activities with GNAS KO in histone modification, mRNA processing, and transcriptional regulation. Collectively, our findings establish an unprecedented link between HDAC3 inhibition and viral mimicry in lymphoma. We suggest low GNAS expression as a potential biomarker that reflects viral mimicry priming for enhanced response to HDAC3 inhibition in the clinical treatment of lymphoma, especially the CREBBP wild-type cases.

RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

Potential utility of ADNP in circulating tumor cells as biomarker for prognostics in non-muscle-invasive bladder cancer.

This study aims to evaluate the prognostic utility of Activity-dependent neuroprotective protein (ADNP) expression in Circulating Tumor Cells (CTCs) inpatients with Non-muscle-invasive Bladder Cancer (NMIBC) undergoing Transurethral Resection of Bladder Tumor (TURBT). A prospective cohort of 74 bladder cancer patients and 22 non-cancer controls were enrolled. The expression of ADNP mRNA was detected by immunomagnetic beads-droplet digital PCR. The ADNP mRNA expression was evaluated in patients with high-risk NMIBC and those with indeterminate invasion depth post 2nd TURBT. Primary cultured bladder cancer cells and PBMCs from healthy donors were immunofluorescence stained. Our findings suggest that baseline ADNP mRNA level in CTCs shows potential as a prognostic marker for NMIBC with a sensitivity of 83.33% and a specificity of 73.58%. In comparison to baseline, ADNP mRNA expression increased post 2nd TURBT in 5 patients, where 2 experienced recurrence. Meanwhile, among the 12 patients with decreased levels, only one patient relapsed. A considerable limitation of this study entails the small sample size. The Immuno-magnetic beads-ddPCR technique provided a viable method for ADNP mRNA detection in CTCs from bladder cancer patients. The preoperative ADNP mRNA level in CTCs was identified as a prognostic indicator for NMIBC. Longitudinal monitoring of ADNP mRNA in CTCs of bladder cancer patients shows promise in evaluating treatment responses and predicting prognosis.

Identifying personalized barriers for hypertension self-management from TASKS framework.

OBJECTIVE: Effective management of hypertension requires not only medical intervention but also significant patient self-management. The challenge, however, lies in the diversity of patients' personal barriers to managing their condition. The objective of this research is to identify and categorize personalized barriers to hypertension self-management using the TASKS framework (Task, Affect, Skills, Knowledge, Stress). This study aims to enhance patient-centered strategies by aligning support with each patient's specific needs, recognizing the diversity in their unique circumstances, beliefs, emotional states, knowledge levels, and access to resources. This research is based on observations from a single study focused on eight patients, which may have been a part of a larger project. RESULTS: The analysis of transcripts from eight patients and the Global Hypertension Practice Guidelines revealed 69 personalized barriers. These barriers were distributed as follows: emotional barriers (49%), knowledge barriers (24%), logical barriers (17%), and resource barriers (10%). The findings highlight the significant impact of emotional and knowledge-related challenges on hypertension self-management, including difficulties in home blood pressure monitoring and the use of monitoring tools. This study emphasizes the need for tailored interventions to address these prevalent barriers and improve hypertension management outcomes.

Heparin-Bead Extraction Enhanced Fluorogenic Aptamer-Thrombin Composite Reporter Enables Sensitive and Rapid Detection of Functional Antithrombin.

Antithrombin (AT) deficiency in the extracorporeal circulation during cardiac surgery leads to uncontrolled inflammation and vascular damage in patients. AT levels decrease in sepsis, major trauma, extracorporeal membrane oxygenation, and eclampsia. Monitoring plasma AT levels facilitates the accurate restoration of AT to baseline values through precise supplementation. Traditional methods of chromogenic assay and enzyme-linked immunosorbent assay (ELISA) kits encounter challenges, such as interference, inconsistency, and delayed response times, making real-time, reliable antithrombin monitoring a clinical gap. To address this critical need, we develop a heparin-bead extraction enhanced fluoroGenic aptamer-thrombin composite reporter (HExGATOR) for the rapid, sensitive, and precise detection of functional AT in plasma. Our design employs thrombin-binding aptamers and a fluorescence "turn on" technology such that a signal is produced upon the interaction of AT with the otherwise "turned off" aptamer-thrombin complex. The prominent signal-background interference originating from plasma is remarkably diminished by using a heparin-bead solid-phase extraction of AT. We achieved highly sensitive and rapid detection of AT in 5 to 20 min with a limit of detection of 15.11 nM. This approach offers a promising alternative to traditional AT tests in clinical settings, potentially facilitating personalized anticoagulant therapy.

Scutellarin ameliorates mitochondrial dysfunction and apoptosis in OGD/R-insulted HT22 cells through mitophagy induction.

Scutellarin (Scu), a flavonoid from herbal Erigeron breviscapus (Vaniot) Hand-Mazz, exerts neuroprotective effects against cerebral ischemia. However, whether the effects of Scu are related to mitochondrial protection needs further investigation. In this study, we aimed to clarify the mechanisms of Scu against HT22 cells injury caused by oxygen-glucose deprivation and reperfusion (OGD/R). Our results proved that Scu significantly reduced the overload of intracellular reactive oxygen species (cellar ROS) and mitochondria reactive oxygen species (mito-ROS), ameliorating oxidative stress damage. TUNEL positive rate, Caspase-3 activity, and Cytochrome c (Cyto-c) expression remarkably decreased following Scu treatment. Meanwhile, Scu could maintain mitochondrial morphology and reverse ultrastructure changes. And mitochondrial membrane potential (MMP), oxygen consumption rate (OCR), adenosine triphosphate (ATP) production and Na+/K+-ATPase activity were obviously promoted. Additionally, Scu was found to stimulate mitophagy level by increasing the expression of LC3, Beclin1, PINK1 and Parkin proteins, as well as promoting the degradation of p62. More importantly, the regulatory effects of Scu on mito-ROS, MMP, ATP, Na+/K+-ATPase, cell viability and lactate dehydrogenase (LDH) were markedly limited by Mdivi-1 (a mitophagy inhibitor). Of note, the inhibitor also reversed Scu-mediated apoptosis suppression, evidenced by the diminished apoptosis rate, the down-regulated expression activities of Cyto-c, Bax and cleaved Caspase-3, as well as the elevated level of Bcl-2 protein. Collectively, Scu could improve mitochondrial dysfunction and inhibit apoptosis by stimulating mitophagy, thereby attenuating OGD/R-induced HT22 cells injury.

Association of anesthesia handovers with perioperative and short-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Anesthesiologists transition patient care to combat clinician fatigue and accommodate shift limitations. Studies exploring the association of increased handovers with patient outcomes have conflicting findings. Here, we investigate the association of anesthesia handovers with perioperative outcomes in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a single institution from 2017 to 2022 were stratified by the number of anesthesia attending and nonattending (nurse anesthetist/resident) handovers (0-1 or ≥2). Primary outcomes were intensive care unit and hospital length of stay, in addition to 30-day serious morbidity. Logistic and negative binomial regression models were adjusted for covariates related to patient and case complexity. RESULTS: A total of 182 patients were included. Median operative time was 720 minutes (interquartile range, 540-900 minutes). Most cases had fewer than 2 attending handovers (n = 147, 81% vs ≥2 handovers n = 35, 19%) and 2 nonattending handovers (n = 120, 71% vs ≥2 handovers n = 53, 29%). In adjusted models, there were no differences in 30-day serious morbidity and intensive care unit or hospital length of stay between the attending handover groups (0-1 vs ≥2). Patients with ≥2 non-attending handovers had similar odds of 30-day serious morbidity compared with the 0-1 group (odds ratio, 1.613, 95% confidence interval, 0.733-3.550, P = .235), but a longer total hospital (incidence rate ratio, 1.301, 95% confidence interval, 1.071-1.579, P = .008) and intensive care unit length of stay (incidence rate ratio 1.548, 95% confidence interval, 1.038-2.049, P = .030). CONCLUSIONS: Multiple anesthesia handovers were not associated with an increased risk of serious morbidity for patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. However, increased handovers (≥2) between nonattending providers was associated with longer hospital and intensive care unit length of stays.

EEG-based study of design creativity: a review on research design, experiments, and analysis.

Brain dynamics associated with design creativity tasks are largely unexplored. Despite significant strides, there is a limited understanding of the brain-behavior during design creation tasks. The objective of this paper is to review the concepts of creativity and design creativity as well as their differences, and to explore the brain dynamics associated with design creativity tasks using electroencephalography (EEG) as a neuroimaging tool. The paper aims to provide essential insights for future researchers in the field of design creativity neurocognition. It seeks to examine fundamental studies, present key findings, and initiate a discussion on associated brain dynamics. The review employs thematic analysis and a forward and backward snowball search methodology with specific inclusion and exclusion criteria to select relevant studies. This search strategy ensured a comprehensive review focused on EEG-based creativity and design creativity experiments. Different components of those experiments such as participants, psychometrics, experiment design, and creativity tasks, are reviewed and then discussed. The review identifies that while some studies have converged on specific findings regarding EEG alpha band activity in creativity experiments, there remain inconsistencies in the literature. The paper underscores the need for further research to unravel the interplays between these cognitive processes. This comprehensive review serves as a valuable resource for readers seeking an understanding of current literature, principal discoveries, and areas where knowledge remains incomplete. It highlights both positive and foundational aspects, identifies gaps, and poses lingering questions to guide future research endeavors.

Differences and correlations between industrial experts and semi-trained assessors in the sensory evaluation of strong-aroma baijiu using rate-all-that-apply.

Baijiu has rich and complex sensory characteristics, and how to make the sensory analysis results given by baijiu industrial experts better understood by consumers has been attracting a lot of attention. In this study, 35 strong-aroma baijiu samples were evaluated by 12 industrial experts and 21 semi-trained assessors, respectively, using rate-all-that-apply (RATA) methods, which involved 2 groups of lexicons generated by the 2 panels. The results showed that the RATA method was suitable for analyzing and distinguishing different baijiu samples by both industrial experts and semi-trained assessors. Although the industrial experts and the semi-trained assessors selected very different lexicons to describe the same strong-aroma baijiu samples, most descriptors from the expert evaluators are either positively or negatively correlated with the semi-trained assessors, such as the attributes "aldehyde," "mud," "multi-grain," and "scorched," and these attributes are effective in distinguishing different strong-aroma baijiu samples. These correlations could enable the marketing promotion and consumer evaluation of baijiu products in the future. PRACTICAL APPLICATION: The result could help baijiu market, in particular the worldwide beverage market, better understand how different baijiu samples are described and evaluated by industrial experts, and further enable the marketing promotion and consumer evaluation of baijiu products in the future.

Immunostimulatory effects of Toll-like receptor ligands as adjuvants in establishing a novel mouse model for pemphigus vulgaris.

BACKGROUND: The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll-like receptor (TLR) ligands as compared to CFA. METHODS: A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein-3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme-linked immunosorbent assay quantified antigen-specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes. RESULTS: TLR ligands demonstrated efficacy in inducing PV-like symptoms in wild-type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self-antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study. CONCLUSIONS: The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis. KEY POINTS/HIGHLIGHTS: Immunization with desmoglein 3 and Toll-like receptor (TLR) ligands effectively induces pemphigus symptoms in wild-type mice, whereas complete Freund's adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10, leading to more effective immune responses.

Percutaneous coronary intervention leads to microplastics entering the blood: Interventional devices are a major source.

Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body.

Disintegrin Accutin inhibits A549 cell migration though suppression of EMT and FAK/AKT signaling pathway.

Integrins are heterodimers composed of two subunits, α(120-185kD) and ß (90-110kD), which mediate the connection between cells and their external environment, such as extracellular matrix (ECM), and play an important role in the regulation of cell shape, proliferation and migration. Herein, we identified a potent anti-tumor migration peptide Accutin from crude venom of Agkistrodon acutus using an A549 3D tumor sphere model, and simulation tools and RNA sequencing were performed to reveal the mechanism of Accutin. Accutin is a disintegrin and docking, molecular dynamics simulations and ITC assay indicate that the RGD motif in the Accutin sequence can stably bind to integrins α5ß1. 9.22 nM Accutin can significantly inhibit the migration and invasion of lung cancer cell lines. Transcriptome analysis indicated that many genes are involved in tumor cell adhesion-related biological processes. Several pathways, like the "mTOR signaling pathway", "TGF-ß signaling pathway", and "Focal adhesion" were enriched. Interestingly, pathways involved in "N-Glycan biosynthesis" etc. were significantly inhibited. These transcriptomics data suggested that the molecular basis of Accutin-mediated inhibition of cancer cell migration may be by inhibiting N-glycosylation of integrin, then inhibiting signaling pathways such as PI3K/AKT/mTOR and TGFß/smad. Western blotting analysis further confirmed that Accutin could suppress migration via down-regulating the phosphorylation of FAK and AKT and inhibiting EMT (epithelial-mesenchymal transition). Taken together, as a disintegrin with high efficiency, Accutin may be a potential precursor of a therapeutic agent for the treatment of lung cancer migration.

Relationship between childhood trauma and non-suicidal self-injury in high school students: the mediating role of the stress perception and the moderating role of teacher-student relationship.

This study delves into the correlation between childhood trauma and non-suicidal self-injury (NSSI) behaviors among high school students. Additionally, it examines the mediating role of stress perception and the moderating role of the teacher-student relationship in this association. A questionnaire survey was administered to 1,329 high school students in Yunnan Province to assess childhood trauma, NSSI behaviors, and stress perception. Firstly, the survey revealed a 12% prevalence of NSSI, with girls exhibiting a higher occurrence compared to boys (OR = 0.413, 95% CI: 0.280-0.609). Secondly, childhood trauma emerged as a significant predictor of NSSI behavior, irrespective of gender or whether the individual was an only child (r = 0.17, P < 0.01). Thirdly, stress perception functioned as a mediator in the relationship between childhood trauma and NSSI among high school students (t = 4.65, P < 0.01). The mediation effect occupies 26.56% of the total effect. Furthermore, the teacher-student relationship moderated the mediating effect of stress perception on the link between childhood trauma and NSSI (ß = 0.0736, P < 0.01). Notably, individuals with strong teacher-student relationships exhibited a significant elevation in stress perception upon exposure to childhood trauma. The findings of this study support a moderated mediation model in the association between childhood trauma and NSSI, suggesting profound implications for the development of targeted interventions and prevention strategies among high school students.

FTO mediates bisphenol F-induced blood-testis barrier impairment through regulating ferroptosis via YTHDF1/TfRc and YTHDF2/SLC7A11 signal axis.

Bisphenol F (BPF) has been extensively utilized in daily life, which brings new hazards to male reproductive health. However, the specific functional mechanism is still unclear. Both cell and animal models were utilized for exploring the role of RNA methylation and ferroptosis and its underlying mechanisms in male reproductive injury induced by BPF. In animal model, BPF severely destroyed the integrity of the blood-testis barrier (BTB) and induced ferroptosis. Furthermore, BPF significantly affected the barrier function of TM4 cells and promoted ferroptosis. Importantly, ChIP assays revealed that BPF inhibited AR transcriptional regulation of FTO and FTO expression was downregulated in TM4 cells. Overexpression of FTO prevented the impairment of BTB by inhibiting ferroptosis in TM4 cells. Mechanistically, FTO could significantly down-regulate the m6A modification level of TfRc and SLC7A11 mRNA through MeRIP experiment. RIP experiments showed that YTHDF1 can bind to TfRc mRNA and promote its translation while YTHDF2 could bind to SLC7A11 mRNA and reduce its mRNA stability. Therefore, our results suggest that FTO plays a key role in BPF induced male reproductive toxicity through YTHDF1-TfRc axis and YTHDF2-SLC7A11 axis and may provide new ideas and methods for the prevention and treatment of male reproductive diseases associated with environmental pollutants.

Clinical application of liquid biopsy in colorectal cancer: detection, prediction, and treatment monitoring.

Colorectal cancer (CRC) is one of the most prevalent malignancies affecting the gastrointestinal tract and is ranked third among cancers with the highest incidence and second-highest mortality rate worldwide. CRC exhibits a slow progression providing a wide treatment window. The currently employed CRC screening methods have shown great potential to prevent CRC and reduce CRC-related morbidity and mortality. The diagnosis of CRC is achieved by colonoscopy and tissue biopsy, with studies showing that liquid biopsy is more effective in detecting and diagnosing early CRC patients. Increasing number of studies have shown that the tumor components shed into circulating blood can be detected in liquid form, and can be applied in the clinical management of CRC. Analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or tumor-associated platelets (TEPs) in the blood can be used for early screening and diagnosis of CRC, aid tumor staging, treatment response monitoring, and prediction of CRC recurrence and metastasis in a minimally invasive manner. This chapter provides an updated review of CTCs, ctDNA, and TEPs as novel biomarkers for CRC, highlighting their strengths and limitations.

The spatial pattern of Populus euphratica competition based on competitive exclusion theory.

Introduction: Population-level competition and spatial patterns may explain the role of competitive exclusion in communities, which is important for vegetation restoration and biodiversity conservation. Methods: We analyzed the competitive intensity, spatial patterns, and renewal of Populus euphratica Oliv. forests in the Tarim River Basin using the Hegyi competition index and spatial point pattern analysis in a completely random model with different habitats and different forest ages. Results: The greatest competitive distance for P. euphratica was 10 m, and the intensity of competition steadily decreased as the diameter increased. The intensity of intraspecific and interspecific competition in young, mature, and old P. euphratica forests was as follows: riverside habitat > transitional habitat > desert margin habitat. The Simpson index values for the three habitats decreased as follows: transitional > riverside > desert margin, and the Shannon-Wiener index and Pielou index values decreased as follows: riverside > transitional > desert margin. In the riverside habitat, the young P. euphratica forest experienced the greatest competitive intensity, the mature forest in the transitional habitat was the largest, and the forest in the desert margin habitat was the oldest. Competitive intensity was greatest in the young riverside P. euphratica forest, mature P. euphratica forest in the transitional habitat, and old forest in the desert margin. Riverside P. euphratica experienced strong competition from Populus pruinosa. Competitive exclusion caused P. pruinosa to disappear from the transitional and desert margin habitats. Young, mature, and old P. euphratica forests were randomly distributed along the riverside and in the transitional habitat, while mature and old P. euphratica forests were randomly distributed in the desert margin. Populus pruinosa, Tamarix ramosissima, and Tamarix hispida were mainly randomly distributed, and T. ramosissima and T. hispida were clustered at small scales. In the riverside habitat, young, mature, and old P. euphratica had no spatial correlation, and there was a significant negative correlation at small scales in the transitional habitat. The density of P. euphratica seedlings in the riverside habitat was greater than that in the transitional habitat, and greater competitive pressures on P. euphratica tree seedlings caused a lower renewal density. Conclusions: When planting P. euphratica forests, spacing greater than 10 m can effectively reduce stand competition and thus promote seedling regeneration.

Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS.

Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.

Benzo(a)pyrene promotes the malignant progression of malignant-transformed BEAS-2B cells by regulating YTH N6-methyladenosine RNA binding protein 1 to inhibit ferroptosis.

Benzo[a]pyrene (BaP) is associated with the development of lung cancer, but the underlying mechanism has not been completely clarified. Here, we used 10 µM BaP to induce malignant transformation of human bronchial epithelial BEAS-2B cells, named BEAS-2B-T. Results indicated that BaP (6.25, 12.5 and 25 µM) treatment significantly promoted the migration and invasion of BEAS-2B-T cells. Meanwhile, BaP exposure inhibited ferroptosis in BEAS-2B-T, ferroptosis-related indexes Fe2+, malondialdehyde (MDA), lipid peroxidation (LPO) and reactive oxygen species (ROS) decreased significantly. The protein level of ferroptosis-related molecule transferrin receptor (TFRC) decreased significantly, while solute carrier family 7 membrane 11 (SLC7A11), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) increased significantly. The intervention of ferroptosis dramatically effected the migration and invasion of BEAS-2B-T induced by BaP. Furthermore, the expression of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) was markedly increased after BaP exposure. YTHDF1 knockdown inhibited BEAS-2B-T migration and invasion by promoting ferroptosis. In the meantime, the contents of Fe2+, MDA, LPO and ROS increased significantly, TFRC was markedly increased, and SLC7A11, FTH1, and GPX4 were markedly decreased. Moreover, overexpression of YTHDF1 promoted BEAS-2B-T migration and invasion by inhibiting ferroptosis. Importantly, knockdown of YTHDF1 promoted ferroptosis and reduced BEAS-2B-T migration and invasion during BaP exposure, and overexpression of YTHDF1 increased migration and invasion of BEAS-2B-T by inhibiting ferroptosis during BaP exposure. RNA immunoprecipitation assays indicated that the binding of YTHDF1 to SLC7A11 and FTH1 markedly increased after YTHDF1 overexpression. Therefore, we concluded that BaP promotes the malignant progression of BEAS-2B-T cells through YTHDF1 upregulating SLC7A11 and FTH1 to inhibit ferroptosis. This study reveals new epigenetic and ferroptosis markers for preventing and treating lung cancer induced by environmental carcinogens.