Apigenin improves testosterone synthesis by regulating endoplasmic reticulum stress.

Obesity is a growing epidemic among reproductive-age men, which can cause and exacerbate male infertility by means of associated comorbidities, endocrine abnormalities, and direct effects on the fidelity and throughput of spermatogenesis. A prominent consequence of male obesity is a reduction in testosterone levels. Natural products have shown tremendous potential anti-obesity effects in metabolic diseases. This study aimed to investigate the potential of apigenin (AP) to alleviate testicular dysfunction induced by a high-fat diet (HFD) and to investigate the underlying mechanisms, focusing on endoplasmic reticulum stress (ERS) and testosterone synthesis. A murine model of obesity was established using HFD-fed mice. The effects of AP on obesity, lipid metabolism, testicular dysfunction, and ERS were assessed through various physiological, histological, and molecular techniques. Administration of AP (10 mg/kg) ameliorated HFD-induced obesity and testicular dysfunction in a mouse model, as evidenced by decreased body weight, improved lipid profiles and testicular pathology, and restored protein levels related to testosterone. Furthermore, in vitro studies demonstrated that AP relieved ERS and recovered testosterone synthesis in murine Leydig cells (TM3) treated with free fatty acids (FFAs). It was also observed that AP rescued testosterone synthesis enzymes in TM3 cells, similar to that observed with the inhibitor of the PERK pathway (GSK2606414). In addition, ChIP, qPCR, and gene silencing showed that the C/EBP homologous protein (CHOP) bound directly to the promoter region of steroidogenic STAR and negatively modulated its expression. Collectively, AP has remarkable potential to alleviate HFD-induced obesity and testicular dysfunction. Its protective effects are attributable partly to mitigating ERS and restoring testosterone synthesis in Leydig cells.

GRP78/IRE1 and cGAS/STING pathway crosstalk through CHOP facilitates iodoacetic acid-mediated testosterone decline.

Iodoacetic acid (IAA) is an emerging unregulated iodinated disinfection byproduct with high toxicity and widespread exposure. IAA has potential reproductive toxicity and could damage male reproduction. However, the underlying mechanisms and toxicological targets of IAA on male reproductive impairment are still unclear, and thus Sprague-Dawley rats and Leydig cells were used in this work to decode these pending concerns. Results showed that after IAA exposure, the histomorphology and ultrastructure of rat testes were abnormally changed, numbers of Leydig cells were reduced, the hypothalamic-pituitary-testis (HPT) axis was disordered, and testosterone biosynthesis was inhibited. Proteomics analyses displayed that oxidative stress, endoplasmic reticulum stress, and steroid hormone biosynthesis were involved in IAA-caused reproductive injury. Antioxidant enzymes were depleted, while levels of ROS, MDA, 8-OHdG, and γ-H2A.X were increased by IAA. IAA triggered oxidative stress and DNA damage, and then activated the GRP78/IRE1/XBP1s and cGAS/STING/NF-κB pathways in Leydig cells. The two signaling pathways constructed an interactive network by synergistically regulating the downstream transcription factor CHOP, which in turn directly bound to and negatively modulated steroidogenic StAR, finally refraining testosterone biosynthesis in Leydig cells. Collectively, IAA as a reproductive toxicant has anti-androgenic effects, and the GRP78/IRE1 and cGAS/STING pathway crosstalk through CHOP facilitates IAA-mediated testosterone decline.

Polystyrene microplastics trigger testosterone decline via GPX1.

As an emerging environmental endocrine disruptor, polystyrene microplastics (PS-MPs) are considered to have the anti-androgenic feature and impair male reproductive function. To explore the adverse effects of PS-MPs on testosterone synthesis and male reproduction and further elucidate underlying mechanisms, BALB/c mice and Leydig cells were employed in the present work. The results indicated that 50 µm PS-MPs accumulated in mouse testes and were internalized into the cytoplasm. This not only damaged the testicular histomorphology and ultrastructure, but also reduced the viability of Leydig cells and the serum level of GnRH, FSH, LH, and testosterone. After PS-MPs exposure, the ubiquitination degradation and miR-425-3p-targeted modulation synergistically contributed to the suppression of GPX1, which induced oxidative stress and subsequently activated the PERK-EIF2α-ATF4-CHOP pathway of endoplasmic reticulum (ER) stress. The transcription factor CHOP positively regulated the expression of SRD5A2 by directly binding to its promoter region, thereby accelerating testosterone metabolism and ultimately lowing testosterone levels. Besides, PS-MPs compromised testosterone homeostasis via interfering with the hypothalamic-pituitary-testis (HPT) axis. Taken together, PS-MPs possess an anti-androgenic characteristic and exert male reproductive damage effects. The antioxidant enzyme GPX1 plays a crucial role in the PS-MPs-mediated testosterone decline.

Weed detection and recognition in complex wheat fields based on an improved YOLOv7.

Introduction: The precise detection of weeds in the field is the premise of implementing weed management. However, the similar color, morphology, and occlusion between wheat and weeds pose a challenge to the detection of weeds. In this study, a CSCW-YOLOv7 based on an improved YOLOv7 architecture was proposed to identify five types of weeds in complex wheat fields. Methods: First, a dataset was constructed for five weeds that are commonly found, namely, Descurainia sophia, thistle, golden saxifrage, shepherd's purse herb, and Artemisia argyi. Second, a wheat weed detection model called CSCW-YOLOv7 was proposed to achieve the accurate identification and classification of wheat weeds. In the CSCW-YOLOv7, the CARAFE operator was introduced as an up-sampling algorithm to improve the recognition of small targets. Then, the Squeeze-and-Excitation (SE) network was added to the Extended Latent Attention Networks (ELAN) module in the backbone network and the concatenation layer in the feature fusion module to enhance important weed features and suppress irrelevant features. In addition, the contextual transformer (CoT) module, a transformer-based architectural design, was used to capture global information and enhance self-attention by mining contextual information between neighboring keys. Finally, the Wise Intersection over Union (WIoU) loss function introducing a dynamic nonmonotonic focusing mechanism was employed to better predict the bounding boxes of the occluded weed. Results and discussion: The ablation experiment results showed that the CSCW-YOLOv7 achieved the best performance among the other models. The accuracy, recall, and mean average precision (mAP) values of the CSCW-YOLOv7 were 97.7%, 98%, and 94.4%, respectively. Compared with the baseline YOLOv7, the improved CSCW-YOLOv7 obtained precision, recall, and mAP increases of 1.8%, 1%, and 2.1%, respectively. Meanwhile, the parameters were compressed by 10.7% with a 3.8-MB reduction, resulting in a 10% decrease in floating-point operations per second (FLOPs). The Gradient-weighted Class Activation Mapping (Grad-CAM) visualization method suggested that the CSCW-YOLOv7 can learn a more representative set of features that can help better locate the weeds of different scales in complex field environments. In addition, the performance of the CSCW-YOLOv7 was compared to the widely used deep learning models, and results indicated that the CSCW-YOLOv7 exhibits a better ability to distinguish the overlapped weeds and small-scale weeds. The overall results suggest that the CSCW-YOLOv7 is a promising tool for the detection of weeds and has great potential for field applications.

Wilms' Tumor 1-Associating Protein Promotes Nonsmall-Cell Lung Cancer Through the Expression of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5.

OBJECTIVES: This study aimed to analyze the functional roles and molecular mechanism of Wilms' tumor 1-associating protein (WTAP) in the tumorigenesis of nonsmall-cell lung cancer (NSCLC). METHODS: Retrospective analysis was used. Tumor tissues and surrounding nontumor tissues of 150 patients with NSCLS who were surgically resected in the Fourth Hospital of Hebei Medical University from January 2016 to January 2018 were selected. The expression of WTAP in NSCLC tissues was detected by immunohistochemistry. Clinicopathologic parameters were then subjected to univariate and multivariate Cox regression analysis in purpose of uncovering the independent risk factors for overall survival time. MTS (3-[4,5-dimethylthiazol-zyl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazoliuzolium, inner salt) assay, colony formation assay, and transwell assays were performed to estimate cell proliferation, migration, and invasion. Meanwhile, the relationship between WTAP and the cell migration and invasion marker-related proteins were evaluated by Western blot analysis and RT-qPCR. WTAP expression was knocked-down in cell lines by shRNA, and RNA-Seq was performed to investigate the pathways regulated by WTAP. RESULTS: In NSCLC patients, WTAP was highly expressed in tumor tissues and the higher expression was significantly associated with poor overall survival (OS) (P<0.01). Compared with the control group in vitro, the overexpression of WTAP could significantly promote cell proliferation, migration, and invasion (P<0.01), while knock-down WTAP significantly reduces the above effects (P<0.01). In a mouse orthotopic implantation model, higher WTAP abundance could significantly promote tumor enlargement compared with the control group (P<0.01). Compared with the control group, the knock-down of WTAP significantly inhibit the expression of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in cell lines (P<0.01). Besides, in NSCLC, knocked-down CEACAM5 significantly reduced the impact of WTAP on cell proliferation, migration, and invasion compared with the control group (P<0.05). CONCLUSIONS: This study suggests that high expression of WTAP was associated with poor clinical outcomes. CEACAM5 may play a synergistic role with WTAP to jointly promote NSCLC progression by enhancing cell proliferation, invasion, and migration.

Label-Free Measurement of CD63 Positive Extracellular Vesicles Using Terahertz Chemical Microscopy.

Extracellular vesicles (EVs) are small cellular organelles involved in intracellular signaling and cell-to-cell interactions. Recent studies suggested that exosomes may have potential applications in the diagnosis and treatment of cancer and neurodegenerative diseases. In this study, extracellular vesicles of the human nonsmall cell lung cancer cell line H1299 and the unlabeled antiCD63 antibody were imaged using a new label-free terahertz chemical microscopy (TCM) technique to detect changes in the terahertz wave amplitude. To verify the high specificity of the protein biomarkers and the sensitivity of the biosensor surface, we also confirmed the selective binding of the antibody to the antigen, bovine serum albumin, and cancer cells. We also performed real-time measurements of the interaction between EVs from the H1299 cell and the antiCD63 antibody, which showed that the amount of change in the terahertz intensity increased with increasing concentration and the time to saturation decreased. Finally, to reuse the used biosensors (sensing plates), plasma-oxygen cleaning was used, and the activity of the biosensor surface was confirmed by terahertz microscopy and atomic force microscopy and was found to be reusable after less than 3 min of cleaning. Consequently, terahertz chemical microscopy was able to detect the presence or absence of antigen-antibody binding and its reaction rate and binding strength.

A novel P/N/Si/Zn-containing hybrid flame retardant for enhancing flame retardancy and smoke suppression of epoxy resins.

Currently, additively efficient flame retardants are being developed to enhance the smoke suppression, flame retardancy, and thermal properties of composite materials. To this end, the current study designed and prepared a novel P/N/Si/Zn-containing organic-inorganic hybrid denoted as APHZ. Its inorganic part was 2-methylimidazole zinc salt (ZIF-8), which improved its smoke suppression and catalytic carbonization. The organic part (P/N/Si-containing compound) promoted its flame retardancy and interfacial compatibility between APHZ and epoxy resin (EP). The test results revealed that EP/APHZ-3 composites achieved a V-0 rating and a notable LOI value of 30.7% when introducing 3 wt% APHZ into the EP matrix. Cone calorimetry tests (CCT) further demonstrated that the average heat release rate (av-HRR), total smoke production (TSP), and CO production (COP) of EP/APHZ-3 were reduced by 23.3%, 14.0%, and 21.1%, respectively. Meanwhile, the char residual was increased by 60.6%, as compared to pure EP. Furthermore, the flame-retardant mechanism of EP/APHZ composites was investigated by the XPS, TG-FTIR, and Raman spectroscopy techniques. The observed synergistic effect of the imidazole skeleton ZIF-8 and P/N/Si-containing compound in APHZ facilitated the generation of a dense multi-element char layer, with the condensed phase flame-retardant mechanism playing a dominant role. These findings contribute to developing and designing high-performance flame-retardant EP.

Effects of Astaxanthin Supplementation on Fatigue, Motor Function and Cognition: A Meta-Analysis of Randomized Controlled Trials.

Dietary astaxanthin supplementation has been demonstrated to have many beneficial and health-promoting effects. The purpose of this systematic review and meta-analysis was to assess the effect of astaxanthin supplementation on fatigue, cognition, and exercise efficiency. A total of 11 randomized controlled trials (RCTs) with 346 healthy participants were included. The random effects model and pooled standardized mean difference (SMDs) were used according to Hedge's g for the meta-analysis, and a meta-regression was also conducted. The results of the two existing studies showed a positive trend for astaxanthin in subjective fatigue relief. The effects of astaxanthin supplementation for 8-12 weeks on cognitive accuracy were marginally significant (SMD: .12; 95% CI: -.02-.26) and on reaction time was not significant (SMD: -.08; 95% CI: -.26 to .10). Remarkably, astaxanthin supplementation combined with regular training could enhance the fat oxidation (SMD: 2.56; 95% CI: 1.24-3.89), and significantly improve the physical performance (SMD: .62; 95% CI: .17-1.06). The subgroup analysis further showed significantly greater benefits when performing the aerobic exercises performance (SMD: .45; 95% CI: .13-.76), when the dose was ≥ 20 mg (SMD: .37; 95% CI: .11-.63), and when the supplementation duration was > 12 weeks (SMD: .66; 95% CI: .13-.63). We conclude that astaxanthin supplementation could significantly enhance aerobic exercise efficiency, especially at higher doses and for longer durations. Further studies based on large sample sizes are imperatively warranted.

Prenatal exposures to phthalates and bisphenols in relation to oxidative stress: single pollutant and mixtures analyses.

Prenatal exposures to phthalates and bisphenols have been shown to be linked with adverse birth outcomes. Oxidative stress (OS) is considered a potential mechanism. The objective of this study was to explore the individual and mixtures of prenatal exposures to phthalates and bisphenols in associations with OS biomarkers. We measured eight phthalate metabolites and three bisphenols in the urine samples from 105 pregnant women in Wuhan, China. Urinary 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F2α (8-isoPGF2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) were determined as OS biomarkers. The OS biomarkers in associations with the individual chemicals were estimated by linear regression models and restricted cubic spline (RCS) models, and their associations with the chemical mixtures were explored by quantile g-computation (qg-comp) models. In single-pollutant analyses, five phthalate metabolites including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-(2-ethylhexyl) phthalate (MEHP), (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) were positively associated with urinary 8-OHdG levels (all FDR-adjusted P = 0.06). These associations were further confirmed by the RCS models and were linear (P for overall association ≤ 0.05 and P for non-linear association > 0.05). In mixture analyses, qg-comp models showed that a one-quartile increase in the chemical mixtures of phthalate metabolites and bisphenols was positively associated with urinary levels of 8-OHdG and 8-isoPGF2α, and bisphenol A (BPA) and bisphenol F (BPF) were the most contributing chemicals, respectively. Prenatal exposures to individual phthalates and mixtures of phthalates and bisphenols were associated with higher OS levels.

Imidazolium-Based Main-Chain Copolymers With Alternating Sequences for Broad-Spectrum Bactericidal Activity and Eradication of Bacterial Biofilms.

In response to the escalating challenge of bacterial drug resistance, the imperative to counteract planktonic cell proliferation and eliminate entrenched biofilms underscores the necessity for cationic polymeric antibacterials. However, limited efficacy and cytotoxicity challenge their practical use. Here, novel imidazolium-based main-chain copolymers with imidazolium (PIm+) as the cationic component are introduced. By adjusting precursor molecules, hydrophobicity and cationic density of each unit are fine-tuned, resulting in broad-spectrum bactericidal activity against clinically relevant pathogens. PIm+1 stands out for its potent antibacterial performance, with a minimum inhibitory concentration of 32 µg mL-1 against Methicillin-resistant Staphylococcus aureus (MRSA), and substantial biofilm reduction in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms. The bactericidal mechanism involves disrupting the outer and cytoplasmic membranes, depolarizing the cytoplasmic membrane, and triggering intracellular reactive oxygen species (ROS) generation. Collectively, this study postulates the potential of imidazolium-based main-chain copolymers, systematically tailored in their sequences, to serve as a promising candidate in combatting drug-resistant bacterial infections.

Analysis of surface water area dynamics and driving forces in the Bosten Lake basin based on GEE and SEM for the period 2000 to 2021.

As an inland dryland lake basin, the rivers and lakes within the Lake Bosten basin provide scarce but valuable water resources for a fragile environment and play a vital role in the development and sustainability of the local societies. Based on the Google Earth Engine (GEE) platform, combined with the geographic information system (GIS) and remote sensing (RS) technology, we used the index WI2019 to extract and analyze the water body area changes of the Bosten Lake basin from 2000 to 2021 when the threshold value is -0.25 and the slope mask is 8°. The driving factors of water body area changes were also analyzed using the partial least squares-structural equation model (PLS-SEM). The result shows that in the last 20 years, the area of water bodies in the Bosten Lake basin generally fluctuated during the dry, wet, and permanent seasons, with a decreasing trend from 2000 to 2015 and an increasing trend between 2015 and 2019 followed by a steadily decreasing trend afterward. The main driver of the change in wet season water bodies in the Bosten Lake basin is the climatic factors, with anthropogenic factors having a greater influence on the water body area of dry season and permanent season than that of wet season. Our study achieved an accurate and convenient extraction of water body area and drivers, providing up-to-date information to fully understand the spatial and temporal variation of surface water body area and its drivers in the basin, which can be used to effectively manage water resources.

Self-Rated Health and Semen Quality in Men Undergoing Assisted Reproductive Technology.

Importance: Numerous studies have documented the association of self-rated health (SRH) with chronic diseases. However, few studies have investigated its association with semen quality. Objective: To examine the association of SRH with semen quality among men undergoing assisted reproductive technology (ART) in China. Design, Setting, and Participants: This cross-sectional study recruited male partners in couples undergoing ART treatment at the Center for Reproductive Medicine, Tongji Hospital, Wuhan, China. A total of 1262 men underwent 2 semen examinations and completed a questionnaire on SRH between December 2018 and January 2020. Data analysis was performed from November 20, 2022, to March 24, 2023. Exposure: SRH, including overall physical and mental health, as well as reproductive-related physical and mental health specifically, were reported at baseline recruitment. Main Outcomes and Measures: Sperm concentration, sperm progressive motility, sperm motility, and sperm count as semen quality parameters. Results: The study included 1262 men with a mean (SD) age of 32.79 (5.25) years and body mass index of 24.37 (3.68). Men with poorer SRH had lower semen quality (eg, sperm concentration among poor vs very good overall physical health: percentage variation, -14.67%; 95% CI, -23.62% to -4.66%). Among 4 components of SRH, a greater reduction in semen quality was estimated for reproductive-related SRH compared with overall SRH, whereas the greatest reduction was observed for reproductive-related physical SRH. In comparison with men with very good reproductive-related physical SRH, men with poor reproductive-related physical SRH had differences of -24.78% (95% CI, -32.71% to -15.93%) and -25.61% (95% CI, -33.95% to -16.22%) in sperm count and concentration, respectively, and regression coefficients of -9.38 (95% CI, -12.01 to -6.76) and -9.24 (95% CI, -11.82 to -6.66) for sperm motility and sperm progressive motility, respectively. Conclusions and Relevance: In this cross-sectional study of Chinese men, poorer SRH was associated with lower semen quality, and reproductive-related physical SRH was the most pronounced indicator. Our findings suggest that SRH, especially reproductive-related physical SRH, was a good indicator of semen quality, which should inform public and clinical regulatory decisions.

Redox Gating for Colossal Carrier Modulation and Unique Phase Control.

Redox gating, a novel approach distinct from conventional electrolyte gating, combines reversible redox functionalities with common ionic electrolyte moieties to engineer charge transport, enabling power-efficient electronic phase control. This study achieves a colossal sheet carrier density modulation beyond 1016 cm-2, sustainable over thousands of cycles, all within the sub-volt regime for functional oxide thin films. The key advantage of this method lies in the controlled injection of a large quantity of carriers from the electrolyte into the channel material without the deleterious effects associated with traditional electrolyte gating processes such as the production of ionic defects or intercalated species. The redox gating approach offers a simple and practical means of decoupling electrical and structural phase transitions, enabling the isostructural metal-insulator transition and improved device endurance. The versatility of redox gating extends across multiple materials, irrespective of their crystallinity, crystallographic orientation, or carrier type (n- or p-type). This inclusivity encompasses functional heterostructures and low-dimensional quantum materials composed of sustainable elements, highlighting the broad applicability and potential of the technique in electronic devices.

Monitoring angiogenesis in skin autografts using photoacoustic microscopy.

BACKGROUND: Skin autografts have been broadly used to manage the skin and soft tissue defects. It is important for surgeons to assess the vitality of skin autografts via observing the angiogenesis. However, there is lack of reliable approach for giving the quantitative angiogenesis information on the skin autografts. Recently, photoacoustic microscopy imaging has attracted much attention based on its good performance in angiography. METHODS: In this study, we aim to monitor angiogenesis in skin autografts via PAM, and further verify its clinical potential for the early prediction of skin autografts clinical outcome. RESULTS AND CONCLUSIONS: The results indicate that PAM is a feasible, precise, high-resolution, noninvasive technique for the early prediction of necrosis of skin autografts via monitoring the angiogenesis, providing a promising tool for surgeons to use this surgical technology.

Urinary biomarkers of drinking-water disinfection byproducts in relation to diminished ovarian reserve risk: A case-control study from the TREE cohort.

BACKGROUND: Disinfection byproducts (DBPs) as ovarian toxicants have been documented in toxicological studies. However, no human studies have explored the effects of exposure to DBPs on diminished ovarian reserve (DOR). OBJECTIVE: To assess whether urinary biomarkers of exposure to drinking-water DBPs were associated with DOR risk. METHODS: A total of 311 women undergoing assisted reproductive technology were diagnosed with DOR in the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. The cases were matched to the controls with normal ovarian reserve function by age in a ratio of 1:1. Urinary trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were quantified as biomarkers of drinking-water DBP exposures. The conditional logistic regression and restricted cubic spline (RCS) were used to explore urinary biomarkers of drinking-water DBP exposures in associations with the risk of DOR. RESULTS: Elevated urinary DCAA levels were associated with higher DOR risk [adjusted odds ratio (OR) = 1.87; 95 % confidence interval (CI): 1.16, 3.03 for the highest vs. lowest quartiles; P for trend = 0.016]. The association was confirmed in the RCS model, with a linear dose-response curve (P for overall association = 0.029 and P for non-linear association = 0.708). The subgroup analysis by age and body mass index (BMI) showed that urinary DCAA in association with DOR risk was observed among women ≥35 years old and leaner women (BMI < 24 kg/m2), but the group differences were not statistically significant. Moreover, a U-shaped dose-response curve between urinary TCAA and DOR risk was estimated in the RCS model (P for overall association = 0.011 and P for non-linear association = 0.004). CONCLUSIONS: Exposure to drinking-water DBPs may contribute to the risk of DOR among women undergoing assisted reproductive technology.

Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Post-device Dimethylamine Treatment Enables Stable and Efficient Perovskite Solar Cells.

The incorporation of organic ligands via post-device treatment is an effective strategy to improve the stability of perovskite solar cells (PSCs). Although the active area is protected by metal electrode under post-treatment, the aggression of post-treatment ligands into active area cannot be avoided thoroughly. Unfortunately, the size of long-chain amines is too large, and the three-dimensional (3D) perovskite cannot maintain its 3D perovskite structure once the cation substitution occurs during the post-treatment. Despite that the low-dimensional (LD) perovskites are beneficial to stability, long-chain amines are harmful to carrier transport in PSCs. Here, we introduce dimethylamine (DMA), a slightly oversized cation that can be doped into 3D perovskite structure, for post-device treatment to improve the efficiency and stability of PSCs. After exposure to DMA gas, the inactive area of Cs/FA/MA mixed cation perovskite device that is not covered by metal electrode is converted into LD perovskite, passivating the defects of 3D perovskite in the active region, suppressing non-radiation recombination and ion migration. As a result, we achieved a power conversion efficiency (PCE) of 22.29 % with negligible hysteresis and better stability after DMA post-treatment, which is much higher than that (20.40 %) of the control device.

3-AP inhibits the growth of human osteosarcoma by decreasing the activity of the iron-dependent pathway.

3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) has broad-spectrum antitumor activity. However, its role in osteosarcoma (OS) remains unclear. Therefore, this study explored the effects of 3-AP on OS in vitro and in vivo using three human OS cell lines (MG-63, U2-OS, and 143B) and a nude mice model generated by transplanting 143B cells. The cells and mice were treated with DMSO (control) or gradient concentrations of 3-AP. Then, various assays (e.g., cell counting kit-8, flow cytometry, immunohistochemistry, and western blotting) were performed to assess cell viability and apoptosis levels, as well as γH2A.X (DNA damage correlation), ribonucleotide reductase catalytic subunit M1 and M2 (RRM1 and RRM2, respectively) protein levels (iron-dependent correlation). 3-AP time- and dose-dependably suppressed growth and induced apoptosis in all three OS cell lines, and ferric ammonium citrate (FAC) blocked these effects. Moreover, 3-AP decreased RRM2 and total ribonucleotide reductase (RRM1 plus RRM2) protein expression but significantly increased γH2A.X expression; treatment did not affect RRM1 expression. Again, FAC treatment attenuated these effects. In vivo, the number of apoptotic cells in the tumor slices increased in the 3-AP-treated mice compared to the control mice. 3-AP treatment also decreased Ki-67 and p21 expression, suggesting inhibited OS growth. Furthermore, the expression of RRM1, RRM2, and transferrin receptor protein 1 (i.e., Tfr1) indicated that 3-AP inhibited OS growth via an iron-dependent pathway. In conclusion, 3-AP exhibits anticancer activity in OS by decreasing the activity of iron-dependent pathways, which could be a promising therapeutic strategy for OS.

Ethanol Extract of Anacyclus pyrethrum Root Ameliorates Cough-Variant Asthma Through the TLR4/NF-κB Pathway and Wnt/ß-Catenin Pathway.

Cough-variant asthma (CVA) has been recognized as the initial stage or pre-asthmatic state of classic asthma, which characterized by cough as the primary clinical presentation. Inhaled glucocorticoids, oral leukotriene receptor antagonists and antihistamines are the clinical treatments, but their efficacy is not satisfactory. Some traditional Chinese medicine (TCM) has been reported to have certain advantages in the treatment of CVA, but the underlying molecular mechanisms are still unclear. Recent research has indicated that Anacyclus pyerhrurm (L) DC. is commonly used in the treatment of human diseases. The aim of our study was to evaluate the anti-inflammatory and anti-oxidative mechanism of the ethanol extract of Anacyclus pyrethrum (L) DC. root (EEAP) in a model of CVA. In our study, we indicated that EEAP ameliorated CVA by reducing cough frequency and inflammatory effect and oxidative stress in an in vivo rat model of CVA. In addition, EEAP ameliorated LPS-induced cell apoptosis and regulated inflammatory effect and oxidative stress in vitro. Mechanistically, EEAP exerted anti-inflammatory effects through regulating the TLR4/NF-κB pathway and Wnt/ß-catenin pathway, and overexpressing TLR4 or activating the Wnt/ß-catenin pathway by SKL2001 reversed EEAP-exerted effects in LPS-exposed BEAS-2B and 16-HBE cells. In conclusion, EEAP attenuated cell apoptosis, inflammation and oxidative stress through restraining the TLR4/NF-κB pathway and Wnt/ß-catenin pathway in CVA, which shown that EEAP might be a promising therapeutic agent for CVA and may provide a theoretical basis for clinical treatment with CVA patients.