Semi-synthetic chondroitin sulfate CS-semi5 upregulates miR-122-5p, conferring a therapeutic effect on osteoarthritis via the p38/MMP13 pathway.

Osteoarthritis (OA) is an aging-associated disease characterized by joint stiffness pain and destroyed articular cartilage. Traditional treatments for OA are limited to alleviating various OA symptoms. There is a lack of drugs available in clinical practice that can truly repair cartilage damage. Here, we developed the chondroitin sulfate analog CS-semi5, semi-synthesized from chondroitin sulfate A. In vivo, CS-semi5 alleviated inflammation, provided analgesic effects, and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model. A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats, revealing miR-122-5p as the key regulator associated with CS-semi5 in OA treatment. Binding prediction revealed that miR-122-5p acted on the 3'-untranslated region of p38 mitogen-activated protein kinase, which was related to MMP13 regulation. Subsequent in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis, which was further validated in the articular cartilage of OA rats. This is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5, revealing its cartilage-protecting, anti-inflammatory, and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.

Melatonin prevents glyphosate-induced hepatic lipid accumulation in roosters via activating Nrf2 pathway.

BACKGROUND: Glyphosate (GLY) is a widely used herbicide with well-defined hepatotoxic effects, in which oxidative stress has been shown to be involved in the pathogenesis of hepatotoxicity. Melatonin (MET), an effective free radical scavenger, has been revealed to alleviate drug-induced liver damage by inhibiting oxidative stress. METHODS: In this study, a rooster model with primary chicken embryo hepatocytes was applied to elucidate the therapeutic effects of MET against GLY-induced hepatic damage and the potential mechanism. Histopathological examinations, biochemical tests and immunoblotting analysis were used to monitor the protective effects of MET on GLY-induced hepatic lipid accumulation. Molecular docking analysis was used to reveal the key reason of MET-improved hepatic lipid deposition. RESULTS: Data firstly showed that MET administration markedly improved GLY-induced hepatic injury, as evidenced by normalized liver enzymes and alleviated pathological changes of liver tissues. Moreover, MET supplementation alleviated GLY-induced hepatic lipid accumulation, which was correlated with improved serum and hepatic lipid profiles and normalized expression of lipolysis- and lipogenesis-related proteins. Notably, MET significantly inhibited vital enzymes involved in stimulating oxidative stress. Moreover, MET enhanced GLY-inhibited Nrf2 nuclear transcription and increased the expressions of its downstream target genes HO1 and NQO1. Further studies revealed that MET may interact with Nrf2 to enhance nuclear translocation of Nrf2. CONCLUSION: Collectively, our results provide the first direct evidence that MET is a novel regulator of Nrf2, highlighting that Nrf2 may be a potential therapeutic target for GLY-induced lipotoxic liver injury.

Chronic dietary exposure to glyphosate-induced connexin 43 autophagic degradation contributes to blood-testis barrier disruption in roosters.

Glyphosate (GLY) is the most universally used herbicide worldwide and its application has caused extensive pollution to the ecological environment. Increasing evidence has revealed the multi-organ toxicity of GLY in different species, but its male reproductive toxicity in avian species remains unknown. Thus, in vivo and in vitro studies were conducted to clarify this issue. Data firstly showed that chronic GLY exposure caused testicular pathological damage. Intriguingly, we identified and verified a marked down-regulation gap junction gene Connexin 43 (Cx43) in GLY-exposed rooster testis by transcriptome analysis. Cx43 generated by Sertoli cells acts as a key component of blood-testis barrier (BTB). To further investigate the cause of GLY-induced downregulation of Cx43 to disrupt BTB, we found that autophagy activation is revealed in GLY-exposed rooster testis and primary avian Sertoli cells. Moreover, GLY-induced Cx43 downregulation was significantly alleviated by ATG5 knockdown or CQ administration, respectively, demonstrating that GLY-induced autophagy activation contributed to Cx43 degradation. Mechanistically, GLY-induced autophagy activation and resultant Cx43 degradation was due to its direct interaction with ER-α. In summary, these findings demonstrate that chronic GLY exposure activates autophagy to induce Cx43 degradation, which causes BTB damage and resultant reproductive toxicity in roosters.

Biosynthesis and Biotechnological Synthesis of Hydroxytyrosol.

Hydroxytyrosol (HT), a plant-derived phenolic compound, is recognized for its potent antioxidant capabilities alongside a spectrum of pharmacological benefits, including anti-inflammatory, anti-cancer, anti-bacterial, and anti-viral properties. These attributes have propelled HT into the spotlight as a premier nutraceutical and food additive, heralding a new era in health and wellness applications. Traditional methods for HT production, encompassing physico-chemical techniques and plant extraction, are increasingly being supplanted by biotechnological approaches. These modern methodologies offer several advantages, notably environmental sustainability, safety, and cost-effectiveness, which align with current demands for green and efficient production processes. This review delves into the biosynthetic pathways of HT, highlighting the enzymatic steps involved and the pivotal role of genetic and metabolic engineering in enhancing HT yield. It also surveys the latest progress in the biotechnological synthesis of HT, examining innovative strategies that leverage both genetically modified and non-modified organisms. Furthermore, this review explores the burgeoning potential of HT as a nutraceutical, underscoring its diverse applications and the implications for human health. Through a detailed examination of both the biosynthesis and biotechnological advances in HT production, this review contributes valuable insights to the field, charting a course towards the sustainable and scalable production of this multifaceted compound.

Curcumin: An innovative approach for postharvest control of Alternaria alternata induced black rot in cherry tomatoes.

Curcumin, a natural bioactive compound derived from Curcuma longa, has been widely recognized for its antifungal properties. In this study, we investigated the effects of curcumin on the phytopathogenic fungus Alternaria alternata and its pathogenicity in cherry tomato fruit. The results demonstrated that curcumin treatment significantly inhibited mycelial growth and spore germination of A. alternata in a dose-dependent manner. Scanning electron microscopy revealed alterations in the morphology of A. alternata mycelia treated with curcumin. Furthermore, curcumin treatment led to an increase in malondialdehyde and hydrogen peroxide contents, indicating cell membrane damage in A. alternata. Moreover, curcumin exhibited a remarkable inhibitory effect on the incidence and lesion diameters of black rot caused by A. alternata in cherry tomato fruit. Gene expression analysis revealed upregulation of defense-related genes (POD, SOD, and CAT) in tomato fruit treated with curcumin. Additionally, curcumin treatment resulted in decreased activity of exocellular pathogenic enzymes (polygalacturonase, pectin lyase, and endo-1,4-ß-d-glucanase) in A. alternata. Overall, our findings highlight the potential of curcumin as an effective antifungal agent against A. alternata, providing insights into its inhibitory mechanisms on mycelial growth, spore germination, and pathogenicity in cherry tomato fruit.

Epidemiology and prognostic factors for new-onset deep venous thrombosis after unicompartmental knee arthroplasty: a retrospective study.

BACKGROUND: Patients who underwent knee joint arthroplasty were at risk of venous thromboembolic events (VTEs), however, less studies were conducted to demonstrate the epidemiology and risk factors of deep venous thrombosis (DVT) following unicompartmental knee arthroplasty (UKA). Objective of this study was to explore the incidence and prognostic factors of DVT after UKA. METHODS: Patients who underwent primary UKA from December 2018 to June 2022 were recruited in this study. Demographic characteristics, operation related variables and laboratory index were extracted and analyzed. Receiver operating characteristic analysis was performed to detect the optimum cut-off value for variables of interest. Univariate and multivariate logistic analysis were performed to identify risk factors of DVT. RESULTS: 351 UKAs with a mean age of 65.4 ± 7.1 years were reviewed. After 12.9 ± 11.2 months follow-up, 35 DVTs were confirmed which indicating an incidence of 9.9%. The results showed that occupation (agricultural laborer) (P = 0.008), disease duration > 8.5 years (P = 0.035), operation time > 169 min (P = 0.003), intraoperative blood loss > 102 ml (P < 0.001), BMI > 26.8 kg/m 2 (P = 0.001), preoperative D-dimer > 0.29 mg/L (P = 0.001), prothrombin time < 10.7 s (P = 0.033) and INR < 0.98 (P = 0.032) between DVT and Non-DVT group were significantly different. Multivariate logistic regression analysis showed intraoperative blood loss > 102 ml (OR, 3.707; P, 0.001), BMI > 26.8 kg/m 2 (OR, 4.664; P, 0.004) and D-dimer > 0.29 mg/L (OR, 2.882; P, 0.009) were independent risk factors of DVT after UKA. CONCLUSION: The incidence of DVT in the present study was 9.9%, extensive intraoperative blood loss, advanced BMI and high level of D-dimer would increase the risk of lower extremity thrombosis by 2-4 times.

Therapeutic effects of coptisine derivative EHLJ7 on colorectal cancer by inhibiting PI3K/AKT pathway.

Colorectal cancer (CRC) is the third most common cancer in the world with high mortality rate. EHLJ7 is a quaternary coptisine derivative synthesized by our institute. In this study, the role and mechanism of EHLJ7 on CRC are further elucidated. Using target fishing, colon cancer-associated target screening and molecular docking analysis, PI3K/AKT pathway was selected for the target of EHLJ7 at CRC. Results of Flow cytometry, wound healing assay and transwell migration assay confirmed that EHLJ7 could inhibit migration and apoptosis of colon cancer cells by specifically inhibiting PI3K/AKT pathway in vitro. Xenograft tumor models and a newly established azoxymethane (AOM)/dextran sulfate sodium (DSS)/Peptostreptococcus anaerobiu (P.anaerobius)-induced CRC mouse model are applied to access the anti-cancer action and mechanism of EHLJ7 using western-blot, immunohistochemistry and analysis of exosomes. The key findings in this study are listed as follows: (1) EHLJ7 exerts superior anti-tumor effect with good safety on Xenograft tumor model and CRC model; (2) EHLJ7 exerted its anti-CRC effect by specifically inhibiting PI3K/AKT pathway and apoptosis in vivo and in vitro. In summary, we demonstrated that EHLJ7 exerts therapeutic effect against CRC by PI3K/AKT pathway, which made it possible as a potentially effective compound for the treatment of CRC.

Observation of the Anomalous Hall Effect in a Layered Polar Semiconductor.

Progress in magnetoelectric materials is hindered by apparently contradictory requirements for time-reversal symmetry broken and polar ferroelectric electronic structure in common ferromagnets and antiferromagnets. Alternative routes can be provided by recent discoveries of a time-reversal symmetry breaking anomalous Hall effect (AHE) in noncollinear magnets and altermagnets, but hitherto reported bulk materials are not polar. Here, the authors report the observation of a spontaneous AHE in doped AgCrSe2 , a layered polar semiconductor with an antiferromagnetic coupling between Cr spins in adjacent layers. The anomalous Hall resistivity 3 µ Ω c m $\mu \Omega \, \textnormal {cm}$ is comparable to the largest observed in compensated magnetic systems to date, and is rapidly switched off when the angle of an applied magnetic field is rotated to ≈80° from the crystalline c-axis. The ionic gating experiments show that the anomalous Hall conductivity magnitude can be enhanced by modulating the p-type carrier density. They also present theoretical results that suggest the AHE is driven by Berry curvature due to noncollinear antiferromagnetic correlations among Cr spins, which are consistent with the previously suggested magnetic ordering in AgCrSe2 . The results open the possibility to study the interplay of magnetic and ferroelectric-like responses in this fascinating class of materials.

Interaction between CSL students' motivation and anxiety under different L2 writing tasks: evidence from Vietnamese university students.

Introduction: Improving task motivation can reduce anxiety and enhance the efficiency of second language (L2) learning. However, previous research has not determined whether the relationship between task motivation and anxiety is unidirectional facilitation or bidirectional interaction. The reasons for these "relationships" and their impact on L2 learning have not been analysed in depth yet. Methods: This study investigated the interaction between task motivation and anxiety via qualitative and quantitative research methods with the participation of 229 Vietnamese university students, who were divided into three L2 writing task groups, including the free choice group (FC), the limited choice group (LC), and the no choice group (NC). Results: The quantitative results show that the higher individuals' autonomy levels were, the higher their task motivation levels would be. Besides, the high level of task anxiety reduced task motivation among Vietnamese university students and exited other anxiety factors. The qualitative analysis of semi-structured interviews conducted with 32 Vietnamese university students showed that a small number of negative factors might trigger low levels of task anxiety. Discussion: Nevertheless, the results for participants with different levels of Chinese language proficiency were highly variable. Participants with better cognitive and Chinese language levels regarded task anxiety as an opportunity to practice their Chinese language skills. They were motivated to complete the task, while participants with lower Chinese language levels exhibited low confidence and experienced more challenges when completing the task.

Highly sensitive analysis of photoregulation and dynamic distribution of phytohormones based on nanoconfined liquid phase nanoextraction.

BACKGROUND: As a vital energy source, light is one of the most significant environmental signals for plants' growth and development. The crosstalk amongst phytohormones regulated by light exhibits quantitative dynamic changes, but methodologies to analyze their distribution during plant growth are still limited. Rapid, highly sensitive, low-invasive detection and simultaneous assessment of the levels of multiple classes of phytohormones have important phytology applications, however the existing sample pretreatment strategies remain intricate, laborious, and far from being developed for in vivo high-sensitivity testing. (81) RESULTS: We applied a nanoconfined liquid phase nanoextraction (NLPNE) technique based on acidified carbon nanofibers (ACNFs) in combination with LC-ESI-MS/MS for highly sensitive analysis of acidic phytohormones' photoregulation and dynamic distribution. In this system, the mass transfer ability of analytes entering the nanoconfined space is significantly improved given the nanoconfined effect. In particular, the accelerated and strong adsorption of alkaline compounds to the ACNFs surface provide minimum interference for acidic compounds (photosensitive phytohormones), which facilitates their simple, fast, and selective quantification with improved sensitivity. The ACNFs-NLPNE strategy achieved quantitative enrichment of multi-class phytohormones in less than 5 min, and detection limits down to 0.49 fg mL-1. Moreover, we monitored the phytohormone changes under red and blue monochromatic light with relative standard deviations <13.4 %. The results further indicated that short-time red light regulation promoted Lepidium sativum L. growth while blue light inhibited it. (141) SIGNIFICANCE: A nanoconfinement effect-based sample pretreatment platform was developed for monitoring photoregulation phytohormones dynamic distribution with higher sensitivity and stability. Our findings highlighted the importance of the NLPNE approach in providing an accurate plant crosstalk information at the molecular level, which opens a promising avenue for investigating internal hormonal responses to external stimuli. (52).

Perioperative sleep disorders in gynaecological daycase surgery patients and analysis of risk factors: protocol for a cross-sectional study.

INTRODUCTION: Sleep disorders are clinical syndromes of disturbed sleep-wake rhythms and abnormal sleep quality. They have various causes, but their main manifestations are difficulty falling asleep, sleep disruption and daytime fatigue. These are common clinical symptoms in perioperative patients, especially in gynaecological patients. There is a lack of research on the factors influencing perioperative sleep disorders in gynaecological patients. The aim of this study is to assess the prevalence of sleep disorders in gynaecological surgery patients and to analyse the possible factors influencing them to provide new ideas for improving sleep disorders in this patient population. METHODS AND ANALYSIS: This cross-sectional, descriptive and observational survey is planned to include 480 gynaecological day surgery patients. All patients who meet the inclusion criteria are eligible to join the study. The study will record preoperative diagnosis, surgical procedure, duration of surgery, type of anaesthesia, anaesthetic drugs, sleep quality, anxiety and depression levels and pain indices 30 days before and 1, 2, 3 and 30 days after surgery. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2022(109)) before the start of recruitment. The results of the study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200064533.

Effect of PI3K/AKT/mTOR signaling pathway-based clustered nursing care combined with papaverine injection on vascular inflammation and vascular crisis after replantation of severed fingers.

This research aimed to investigate the effect of PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target protein of rapamycin) signaling pathway-based clustering care combined with papaverine injection on vascular inflammation and vascular crisis after finger amputation and replantation. 100 patients admitted in General Hospital of Ningxia Medical University from April 2022 to December 2022 for replantation of severed fingers were selected and divided into a control group (n = 50) and an observation group (n = 50) using the randomized grouping principle. The control group received a papaverine injection and general nursing care, the observation group received a papaverine injection and clustered care. The pain score; constipation incidence; replantation finger survival rate; physician, nurse, and patient satisfaction; serum inflammatory factors; vascular crisis parameters; and occurrence of adverse reactions were compared between the two patient groups. Enzyme-linked immunosorbent assay was performed to detect PI3K, AKT, and mTOR protein concentrations in the venous blood of the two groups, and statistical analysis of the data was performed. On postoperative day 7, the pain score and incidence of constipation in the observation group were lower than those in the control group (P < 0.05); the survival rate of reimplanted fingers in the observation group was 88.00%, which was higher than that in the control group 80.00% (P < 0.05); the satisfaction of doctors, nurses, and patients in the observation group was higher than that in the control group; the concentrations of interleukin-1 (IL-1), tumor necrosis factor (TNF-α), blood flow resistance index (RI), and arterial pulsatility index (PI) in the observation group were lower than those in the control group, while the concentration of interleukin-10 (IL-10), vascular diameter, and Vm (mean blood flow velocity) were higher in the observation group than those in the control group; the differences were statistically significant (P < 0.05). The difference in the incidence of adverse reactions between the two groups was not statistically significant (P > 0.05). The concentrations of PI3K, AKT, and mTOR proteins in the observation group were higher than those in the control group (P < 0.05). The concentrations of PI3K, AKT, and mTOR proteins in the observation group were higher than those in the control group (P < 0.05). Overall, these findings suggest that clustered care combined with papaverine injection reduces vascular inflammatory symptoms and vascular crisis in the treatment of severed finger replantation through the PI3K/AKT/mTOR signaling pathway.

Glycyrrhizic acid glycosides reduces extensive tripterygium glycosides-induced lipid deposition in hepatocytes.

Aim: Tripterygium glycosides (TG) extracted from the plant Tripterygium wilfordii Hook F has been used to treat chronic kidney diseases for many years. However, hepatotoxicity limits its clinical application. Glycyrrhizic acid glycosides (GA) can reduce TG hepatotoxicity, however, further investigation into the underlying molecular mechanisms by which GA attenuates TG-induced hepatotoxicity is required. Methods: Sprague‒Dawley rats were randomly divided into the control group, the TG groups (TG189 mg/kg group, TG472.5 mg/kg group), and the TG + GA groups (TG189 mg/kg + GA20.25 mg/kg group, TG472.5 mg/kg + GA20.25 mg/kg group). After 21 consecutive days of intragastric administration, structural and molecular changes in hepatocytes were detected. Results: After 21 days of TG treatment, the serum level of the total bilirubin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol increased in the TG189 mg/kg and TG472.5 mg/kg groups when compared to the control group. High-density lipoprotein cholesterol levels were reduced in both TG groups. The ultrastructure of hepatocytes and the structural integrity of the liver were compromised. In addition, the relevant molecular level of the peroxisome proliferators-activated receptor α (PPARα) and acyl-CoA synthetase long-chain family members (ACSLs) pathway was modulated. With the addition of 20.25 mg/kg GA, the serum biochemical indexes and liver tissue structure ultrastructure of hepatocytes were improved, and the PPARα-ACSLs pathway was corrected. Conclusion: The combined application of GA and TG improved abnormal lipid metabolism, repaired liver structure, reduced lipid deposition in hepatocytes, and reduced TG-induced hepatotoxicity.

Risk Factors and Prediction Methods for Endometriosis Combined with Ureteral Stricture Based on Logistic-Regression Analysis.

OBJECTIVE: This study aimed to explore the risk factors of patients with endometriosis (EMS) and ureteral stricture and to establish a prediction model based on logistic-regression analysis. METHODS: The clinical data of 228 EMS patients in Jiaozhou Central Hospital of Qingdao from May 2019 to May 2022 were selected for a retrospective study. According to the results of ureteroscopic biopsy, they were divided into concurrent (n = 32) and nonconcurrent (n = 196) groups. Univariate analysis was performed on the general data and situations of clinical treatment in both groups. Single factor with statistically significant differences was included in unconditional logistic-regression analysis with multiple factors to explore the risk factors of such patients and establish a prediction model. RESULTS: Overt differences were found in previous history of ureter operation (odds ratio (OR) = 3.711, p = 0.006), course of EMS (OR = 3.987, p = 0.007), presence or absence of haematuria (OR = 3.586, p = 0.009) and lateral abdominal pain (OR = 4.451, p = 0.002), and invasion depth of lesion (OR = 7.271, p < 0.001) between the two groups (p < 0.05), without distinct difference in age, menstrual duration, BMI values, history of dysmenorrhea, previous history of drug therapy, smoking history, and drinking history (p > 0.05). Logistic-regression analysis showed that previous history of ureter operation (a1), course of EMS (b2), occurrence of haematuria (c3) and lateral abdominal pain (d4), and invasion depth of lesion ≥5 mm (e5) were risk factors for EMS combined with ureteral stricture (p < 0.05), taking logit (p) = -4.990 + 1.311a1 + 1.383b2 + 1.277c3 + 1.493d4 + 1.984e5 as regression model. The receiver operating characteristic (ROC) curve analysis based on this model showed that the area under the curve (AUC), standard error, and 95% confidence interval (CI) were 0.813, 0.062, and 0.692-0.934, respectively. One hundred EMS patients were re-included, whose values for predictive sensitivity, specificity, and kappa coefficient were 71.40%, 91.10% and 0.615. CONCLUSIONS: Previous history of ureter operation, course of EMS, occurrence of haematuria and lateral abdominal pain, and invasion depth of lesion ≥5 mm were risk factors for EMS combined with ureteral stricture. Therefore, the use of this model has a certain clinical value.

Mechanisms of Er Chen Tang on Treating Asthma Explored by Network Pharmacology and Experimental Verification.

OBJECTIVE: The aim of this study is to explore the active ingredients of ECT and their targets for asthma and investigate the potential mechanism of ECT on asthma. METHODS: Firstly, the active ingredients and target of ECT were screened for BATMAN and TCMSP, and functional analysis was done via DAVID. Then, the animal model was induced by ovalbumin (OVA) and aluminum hydroxide. Eosinophil (EOS) counts, EOS active substance Eosinophilic cationic protein (ECP) and eotaxin levels were detected following the instruction. Pathological changes in lung tissue were examined by H&E staining and transmission electron microscopy. Interleukin (IL-4, IL-10, IL-13, TNF-α), TIgE and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Finally, the protein expression of the TGF-ß / STAT3 pathway to lung tissue was detected by Western Blot. RESULTS: A total of 450 compounds and 526 target genes were retrieved in Er Chen Tang. Functional analysis indicated that its treatment of asthma was associated with inflammatory factors and fibrosis. In the animal experiment, the results showed that ECT significantly regulated inflammatory cytokine (IL-4, IL-10, IL-13, TNF-α) levels in (P<0.05, P<0.01, reduced EOS number (P<0.05) and also ECP and Eotaxin levels in the blood (P<0.05) in BALF and/or plasma. Bronchial tissue injury was obviously improved on ECT treatment. Associated proteins in TGF-ß / STAT3 pathway were significantly regulated by ECT (P<0.05). CONCLUSION: This study originally provided evidence that the Er Chen Tang was effective in the treatment of asthma symptoms, and its underlying mechanism might be the regulation of inflammatory factor secretion and the TGF-ß/STAT3 signaling pathway.

Effects of subchronic exposure of perfluorooctane sulfonate on cognitive function of mice and its mechanism.

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant, and its potential impact on cognitive function remains unclear. We adopted the C57BL/6J mouse model to investigate the effect of PFOS on cognitive function, as well as the underlying mechanisms. Subchronic exposure was performed by administering PFOS via drinking water for 6 months (at doses of 0, 0.2, and 2.0 mg/kg/day), starting from 10.5 months old. The object recognition ability was tested at 2, 4, and 6 months of exposure, and spatial learning and memory were assessed at endpoint. The apoptosis of neurons and astrocytes in the cortex and hippocampus was analyzed, as well as the potential apoptotic signaling pathways. Our results showed that exposure to PFOS for 6 months caused a decrease in object recognition ability and a decline in learning and spatial memory. PFOS selectively increased apoptosis in neurons of the cerebral cortex and specifically activated the endoplasmic reticulum stress PERK/CHOP signaling pathway. In conclusion, our results confirmed that subchronic exposure to PFOS can lead to cognitive impairment in mice, which might be closely associated with the specific activation of an endoplasmic reticulum stress-induced pro-apoptosis pathway in the cerebral cortex neurons.

[Determination of 12 typical personal care products in human urine samples by ultra performance liquid chromatography-tandem mass spectrometry].

A rapid and sensitive method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 12 typical personal care products (PCPs) in human urine. These PCPs included five paraben preservatives (PBs), five benzophenone UV absorbers (BPs), and two antibacterial agents. Accordingly, 1 mL of the urine sample was mixed with 500 µL of ß-glucuronidase-ammonium acetate buffer solution (enzymatic activities are 500 units/mL) and 75 µL of a mixed internal standard working solution (internal standard contents are 7.5 ng), followed by enzymatic hydrolysis overnight (≥16 h) at 37 ℃ in a water bath. The 12 targeted analytes were enriched and cleaned up using an Oasis HLB solid phase extraction column. Separation was performed on an Acquity BEH C18 column (100 mm×2.1 mm, 1.7 µm) using an acetonitrile-water system as the mobile phase, in negative electrospray ionization (ESI-) multiple reaction monitoring (MRM) mode, for target detection and stable isotope internal standard quantification. The optimal MS conditions were established by optimizing the instrument parameters and comparing two analytical columns (Acquity BEH C18 and Acquity UPLC HSS T3) as well as different types of mobile phases (methanol or acetonitrile as the organic phase) to achieve better chromatographic separation. In order to obtain higher enzymatic and extraction efficiency, different enzymatic conditions, solid phase extraction columns, and elution conditions were investigated. The final results showed that methyl parabens (MeP), benzophenone-3 (BP-3), and triclosan (TCS) showed good linearities in the ranges of 4.00-800, 4.00-800 and 5.00-200 µg/L, respectively, the other targeted compounds showed good linearities in the ranges of 1.00-200 µg/L. The correlation coefficients were all greater than 0.999. The method detection limits (MDLs) were in the range of 0.06-1.09 µg/L, and the method quantification limits (MQLs) ranged from 0.08 to 3.63 µg/L. At three spiked levels, the average recoveries of the 12 targeted analytes ranged from 89.5% to 111.8%. The intra-day and inter-day precisions were 3.7%-8.9% and 2.0%-10.6%, respectively. The results of the matrix effect assessment showed that MeP, ethyl paraben (EtP), and benzophenone-2 (BP-2) exhibited strong matrix effects (26.7%-103.8%); propyl paraben (PrP) exhibited moderate matrix effects (79.2%-112.0%); and the other eight target analytes exhibited weak matrix effects (83.3%-113.8%). The matrix effects of the 12 targeted analytes after correction using the stable isotopic internal standard method ranged from 91.9% to 110.1%. The developed method was successfully applied to the determination of the 12 PCPs in 127 urine samples. Ten typical PCPs were detected, with the overall detection rates ranging from 1.7% to 99.7%, except for benzyl paraben (BzP) and benzophenone-8 (BP-8). The results revealed that the population in this area was widely exposed to PCPs, especially MeP, EtP and PrP; the detection rates and concentrations of these PCPs were found to be very high. Our analytical method is simple and sensitive, and it is expected to be an effective tool for biomonitoring PCPs in human urine samples as part of environmental health studies.

Improved Performance of All-Inorganic Perovskite Light-emitting Diodes via Nanostructured Stamp Imprinting.

Halide perovskites are emerging emitters with excellent optoelectronic properties. Contrary to the large grain fabrication goal in perovskite solar cells, perovskite light-emitting diodes (PeLEDs) based on small grain enable efficient radiative recombination because of relatively higher charge carrier densities due to spatial confinement. However, achieving small-sized grain growth with superior crystal quality and film morphology remains a challenge. In this work, we demonstrated a nanostructured stamp thermal imprinting strategy to boost the surface coverage and improve the crystalline quality of CsPbBr3 film, particularly confine the grain size, leading to the improvement of luminance and efficiency of PeLEDs. We improved the thermal imprinting process utilizing the nanostructured stamp to selectively manipulate the nucleation and growth in the nanoscale region and acquire small-sized grain accompanied by improved crystal quality and surface morphology of the film. By optimizing the imprinting pressure and the period of the nanostructures, appropriate grain size, high surface coverage, small surface roughness and improved crystallization could be achieved synchronously. Finally, the maximum luminance and efficiency of PeLEDs achieved by nanostructured stamp imprinting with a period of 320 nm are 67600 cd/m2 and 16.36 cd/A, respectively. This corresponds to improvements of 123 % in luminance and 100 % in efficiency, compared to that of PeLEDs without the imprinting.

Understanding the importance of motivational intensity in English as a foreign language context: A structural equation modeling analysis.

Introduction: Motivational intensity is the effort learners make in language learning. It is an essential component and a direct measurement of L2 motivation. Few studies have distinguished motivational intensity from motivation and explored its role in learning English as a foreign language (EFL). Methods: This study examined 208 university students from Hong Kong to investigate the factors that affect motivational intensity and explored the relationship between motivational intensity and learning motivation using structural equation modeling (SEM). Results and discussion: The students' motivational intensity was affected by personal factors (daily English-learning time and stage of English learning), family factors (monthly household income and parental attitudes), and school factors (English learning engagement and satisfaction). The differences in personal factors, school factors and monthly household income of family factors among different motivational intensity groups were significant whereas the difference in parental attitudes (family factors) between the high- and the low-motivational intensity groups was insignificant. As for the relationship between motivational intensity and motivation, motivational intensity indirectly affected students' intrinsic interest through their attitudes toward native English speakers (ß = 0.16, p = 0.041 < 0.05). The significant path coefficient from the learning situation to attitudes toward native speakers was negative (p < 0.05), indicating that attitudes toward native speakers decline even when the learning situation improves. This study enriched the theoretical study of motivation theory and provided teaching suggestions for improving EFL learning.

Danlu tongdu tablets: Preclinical safety evaluation and mechanism of hepatotoxicity.

Danlu tongdu tablets (DLTD) is a listed Chinese patent medicine collected in the Pharmacopoeia of the People's Republic of China (version 2020). This prescription has been applied in clinics in China for lumbar spinal stenosis and lumbosacral disc herniations. The wide application of Danlu tongdu in therapy has raised some clinical adverse reactions, such as significant elevation of alanine transaminase (ALT) and aspartate transaminase (AST) in individual patients after use. The present study aimed to investigate the safety of Danlu tongdu and analyze its adverse effects on the liver. The maximum feasible dose (MFD) was used to carry out the acute toxicity tests. Mortality, adverse effects, body weight and food consumption were recorded for up to 14 days post treatment. In the 6-month chronic toxicity test, sprague-dawley rats were randomly divided into four groups according body weight, the experimental groups were administrated to rats at the concentrations of 1.67, 3.34 and 6.67 g/kg/day, whereas the control group was received the ultrapure water (vehicle) only, 10 ml/kg, once a day. The animal's body weight, food consumption was monitored weekly. In addition, their hematological and biochemical parameters, body and organ weights and histopathology, were all measured at specific observation time points. Additionally, we further explored the adverse effects mechanism of Danlu tongdu on the liver through transcriptome analysis. No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 1.67 g/kg and 3.34 g/kg, respectively. We found that mild hypertrophy and hyperplasia of hepatic interlobular bile ducts were detected in some rats with doses of 6.67 g/kg after repeated oral administration of Danlu tongdu for 13 and 26 weeks, but the above changes in liver were reversible. The results of transcriptome sequencing showed that Danlu tongdu had a significant effect on cytochrome P450 enzymes in rat liver, especially cytochrome P450 1 (CYP1) subtype. Therefore, the toxic target organ of Danlu tongdu is the liver and the mechanism of mild liver injury is closely related to the up-regulation of cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression.