The mechanism by which SIRT1 regulates autophagy and EMT in drug-resistant oesophageal cancer cells.

Cancer cell resistance presents a significant clinical challenge. The mechanisms underlying drug resistance in cancer cells are intricate and remain incompletely understood. Notably, tumor cell resistance often coincides with the epithelial-mesenchymal transition (EMT). In this study, we observed an elevation in autophagy levels following the development of drug resistance in oesophageal cancer cells. Inhibition of autophagy led to a reduction in drug-resistant cell migration and the inhibition of EMT. Furthermore, we identified an upregulation of SIRT1 expression in drug-resistant oesophageal cancer cells. Subsequent inhibition of SIRT1 expression in drug-resistant cells resulted in the suppression of autophagy levels, migration ability, and the EMT process. Our additional investigations revealed that a SIRT1 inhibitor effectively curbed tumor growth in human oesophageal cancer xenograft model mice (TE-1, TE-1/PTX) without evident toxic effects. This mechanism appears to be associated with the autophagy levels within the tumor tissue.

Effect of online parent training in promoting language development of children with language delay in Hubei province, China.

BACKGROUND: Training parents to implement language and communication intervention strategies is an effective approach to promote language development for children with language delay. AIMS: This study introduces an online parent training program conducted in Hubei province, China, which was designed to help parents of language-delayed children with a diagnosis of autism spectrum disorder (ASD), developmental language disorder (DLD) or global developmental delay (GDD) apply language intervention strategies into daily interactions and promote their children's language development at home. METHODS & PROCEDURES: The Bethel Hearing and Speaking Training Center Family Training for Early Communication & Language Development (Bethel Family Training Program, BFT) (Bethel HSTC, 2020) was designed to improve the language and communication skills for children with language delay in a naturalistic way. The caregivers (including parents, grandparents and other main caregivers) participated in an 8-h online program, including lectures on milestones in child language development, common misunderstandings of child language development, and three basic family language intervention strategies ('Looking together, playing together, and talking together') incorporating active learning through video analysis and discussion. Tongji Hospital in Hubei then continued with 3 months of online home intervention monitoring to all the caregivers via weekly online Q&As led by BFT certified speech therapists' team. The Gesell Developmental Schedules (GDS) was carried out before the online parent training program and after the 3-month online home intervention monitoring. OUTCOMES & RESULTS: 146 families whose children aged 12-68 months with language delay participated in the online training program. The results of the GDS assessments conducted before and after the program showed that not only did the developmental quotient (DQ) of language improve, but so did the DQ of social behaviour and adaptive behaviour (p < 0.001). There is no between-group difference in the application of three strategies between the ASD group and the DLD or GDD group (p > 0.05). Furthermore, both caregivers' ability to apply 'looking together, playing together, talking together' strategies and the effective interaction time played important roles in improving the child's language abilities. CONCLUSION & IMPLICATIONS: The online parent training focusing on improving daily interaction with children through speech-language stimulation strategies promoted the development of language skills. It is an economic and practical approach for children with language delay who have limited access to local language intervention programs. WHAT THIS PAPER ADDS: What is already known on the subject Parent-implemented language intervention is an effective approach at improving children's language development. Telepractice is an appropriate model of service delivery for audiologists and speech-language therapists and may be the primary mode of service delivery or may supplement in-person services. What this paper adds to the existing knowledge This paper explores the effectiveness of an online parent training program and provides new evidence that online training on language support strategies (looking together, playing together, talking together) followed by home intervention monitoring works for Mandarin-speaking children and it is equally effective for children with ASD and non-ASD diagnosis. What are the potential or actual clinical implications of this work? Developmental behavioural paediatricians and speech-language therapists in countries and areas that lack sufficient training resource for every child will have the option to deliver parent training and home intervention monitoring online, which will save time and cost considerably while offering convenience.

Development and validation of a sensitive UPLC-MS/MS analytical method for GFH009 in rat plasma and its application to toxicokinetics studies.

GFH009 is a potent, highly selective, small molecule that targets and inhibits the activity of the CDK9/cyclin T1 regulatory complex of P-TEFb. This study aimed to develop and validate a highly selective and sensitive ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for precise quantification of GFH009 in rat plasma. This method was subsequently employed for conducting toxicokinetic studies of GFH009 in rats. Plasma was prepared using a simple protein precipitation method by acetonitrile. Chromatographic separation of the analytes was achieved on a BEH C18 analytical column with a rapid 3.0 min run time and a flow rate of 0.5 ml/min. The calibration curves for plasma samples exhibited excellent linearity over a wide concentration range of 1.0-1,000 ng/ml for GFH009. Intra- and inter-day accuracies were within 92.7-105.7%, and precisions were no more than 6.7%. Furthermore, the analyte demonstrated stability under four different storage conditions, with variations of <15.0%. This study pioneers a methodological innovation by introducing a highly reliable, specific and sensitive analytical method for GFH009 in rat plasma. The successful application of this method in toxicokinetic studies further underscores its significance, offering valuable insights for the methodology of clinical pharmacokinetic research.

Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions-a case report.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and restricted, repetitive behaviors. In addition to behavioral interventions and psychotherapies, and pharmacological interventions, in-depth studies of intestinal microbiota in ASD has obvious abnormalities which may effectively influenced in ASD. Several attempts have been made to indicate that microbiota can reduce the occurrence of ASD effectively. Fecal microbiota transplantation (FMT) is a type of biological therapy that involves the transplant of intestinal microbiota from healthy donors into the patient's gastrointestinal tract to improve the gut microenvironment. In this case report, we describe a case of child ASD treated by FMT. The patient have poor response to long-term behavioral interventions. After five rounds of FMT, clinical core symptoms of ASD and gastrointestinal(GI) symptoms were significantly altered. Moreover, the multiple levels of functional development of child were also significantly ameliorated. We found that FMT changed the composition of the intestinal microbiota as well as the metabolites, intestinal inflammatory manifestations, and these changes were consistent with the patient's symptoms. This report suggests further FMT studies in ASD could be worth pursuing, and more studies are needed to validate the effectiveness of FMT in ASD and its mechanisms.

Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance.

OBJECTIVE: This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) for Autism Spectrum Disorder (ASD) screening in the presence of developmental surveillance. METHODS: All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules (GDS). Spearman's correlation coefficients and Kappa values were obtained. Taking GDS as a reference assessment, the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic (ROC) curves. The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). RESULTS: In total, 150 children aged 12-42 months with ASD were enrolled. The developmental quotients of the CNBS-R2016 were correlated with those of the GDS (r=0.62-0.94). The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays (Kappa=0.73-0.89), except for Fine Motor. There was a significant difference between the proportions of Fine Motor, delays detected by the CNBS-R2016 and GDS (86.0% vs. 77.3%). With GDS as a standard, the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor, which was 0.70. In addition, the positive rate of ASD was 100.0% and 93.5% when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used, respectively. CONCLUSION: The CNBS-R2016 performed well in developmental assessment and screening for children with ASD, especially by Communication Warning Behaviors subscale. Therefore, the CNBS-R2016 is worthy of clinical application in children with ASD in China.

Children neuropsychological and behavioral scale-revision 2016 in the early detection of autism spectrum disorder.

Background: The Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) is a widely used developmental assessment tool for children aged 0-6 years in China. The communication warning behavior subscale of CNBS-R2016 is used to assess the symptoms of autism spectrum disorder (ASD), and its value of >30 points indicates ASD based on CNBS-R2016. However, we observed that children with relatively lower values were also diagnosed with ASD later on in clinical practice. Thus, this study aimed to identify the suitable cutoff value for ASD screening recommended by the communication warning behavior of CNBS-R2016. Materials and methods: A total of 90 typically developing (TD) children and 316 children with developmental disorders such as ASD, developmental language disorder (DLD), and global developmental delay (GDD; 130 in the ASD group, 100 in the DLD group, and 86 in the GDD group) were enrolled in this study. All subjects were evaluated based on the CNBS-R2016. The newly recommended cutoff value of communication warning behavior for screening ASD was analyzed with receiver operating curves. Results: Children in the ASD group presented with lower developmental levels than TD, DLD, and GDD groups in overall developmental quotient assessed by CNBS-R2016. We compared the consistency between the scores of communication warning behavior subscale and Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Autism Diagnostic Observation Schedule, second edition (ADOS-2), and clinical diagnosis for the classification of ASD at a value of 30 based on the previously and newly recommended cutoff value of 12 by the CNBS-R2016. The Kappa values between the communication warning behavior and ABC, CARS, ADOS-2, and clinical diagnosis were 0.494, 0.476, 0.137, and 0.529, respectively, with an agreement rate of 76.90%, 76.26%, 52.03%, and 82.27%, respectively, when the cutoff point was 30. The corresponding Kappa values were 0.891, 0.816, 0.613, and 0.844, respectively, and the corresponding agreement rate was 94.62%, 90.82%, 90.54%, and 93.10%, respectively, when the cutoff point was 12. Conclusion: The communication warning behavior subscale of CNBS-R2016 is important for screening ASD. When the communication warning behavior score is 12 points or greater, considerable attention and further comprehensive diagnostic evaluation for ASD are required to achieve the early detection and diagnosis of ASD in children.

Mechanically Induced Highly Efficient Hydrogen Evolution from Water over Piezoelectric SnSe nanosheets.

Piezoelectric nanomaterials open new avenues in driving green catalysis processes (e.g., H2 evolution from water) through harvesting mechanical energy, but their catalytic efficiency is still limited. The predicted enormous piezoelectricity for 2D SnSe, together with its high charge mobility and excellent flexibility, renders it an ideal candidate for stimulating piezocatalysis redox reactions. In this work, few-layer piezoelectric SnSe nanosheets (NSs) are utilized for mechanically induced H2 evolution from water. The finite elemental method simulation demonstrates an unprecedent maximal piezoelectric potential of 44.1 V for a single SnSe NS under a pressure of 100 MPa. A record-breaking piezocurrent density of 0.3 mA cm-2 is obtained for SnSe NSs-based electrode under ultrasonic excitation (100 W, 45 kHz), which is about three orders of magnitude greater than that of reported piezocatalysts. Moreover, an exceptional H2 production rate of 948.4 µmol g-1 h-1 is achieved over the SnSe NSs without any cocatalyst, far exceeding most of the reported piezocatalysts and competitive with the current photocatalysis technology. The findings not only enrich the potential piezocatalysis materials, but also provide useful guidance toward high-efficiency mechanically driven chemical reactions such as H2 evolution from water.

Anatomical study of the inferior extensor retinaculum and the oblique superolateral band: implications for the Brostrom-Gould procedure.

PURPOSE: The Brostrom-Gould procedure is currently the gold standard surgical choice for the treatment of chronic ankle instability; it can significantly improve ankle function and stability in patients. However, recent studies have reported doubts regarding the feasibility of the inferior extensor retinaculum (IER) after Brostrom-Gould and therapeutic effects compared with the Brostrom procedure. The purpose of the present study was to observe the anatomical characteristics of the lateral part of the IER using cadaveric bodies in order to guide the surgical operation of chronic ankle instability. METHODS: Twenty-three cadaveric ankles were dissected. The morphology of the IER and its internal structure was observed and recorded for each ankle. The shortest distance between the Stem ligament of the IER and the anterior fibular periosteum (AFP) was measured and recorded, then attempts were made to suture the Stem to the AFP. RESULTS: Twelve of the cadaveric ankles were observed as having an oblique superolateral band (OSLB) that had a tough texture upward of the lateral IER connecting with SL, as are the characteristics of the oblique superolateral band (OSLB) reported in previous studies. The inner and outer membrane of the OSLB were connected with inner and outer membrane of Stem. The average value of the distance between the Stem and AFP was 11.60 ± 2.71 mm, and the maximum and the minimum distance were 19.04 mm and 6.53 mm, respectively. The P -value (P = 0.2) resulting from a single sample K-S test confirmed that the distribution of distances conformed to normality. None of the SL in the study could be sutured to the AFP. CONCLUSION: The OSLB of the IER has a tough texture and connects with the Stem, and has the potential be utilised in the Brostrom-Gould procedure. However, we do not recommend utilization of the Stem in this operation regardless of the distance between the AFP and the Stem. When the Stem cannot be used to enhance repair in this operation, other solutions can be used for strengthening and to protect the repaired ATFL.

Vertical 2-dimensional heterostructure SnS-SnS2 with built-in electric field on rGO to accelerate charge transfer and improve the shuttle effect of polysulfides.

Traditional carbon materials as sulfur hosts of Li-sulfur(Li-S) cathodes have slightly physical constraint for polysulfides, due to their no-polar property. Therefore, it is necessary to further enhance the affinity between sulfur hosts and polysulfides, and relieve the shuttle effects in the Li- S batteries. Herein, we report a novel vertical 2-dimensional (2D) p-SnS/n-SnS2 heterostructure sheets which grown on the surface of rGO. The excellent electrochemical properties of SnS-SnS2@rGO as Li-S cathode are ascribed to the stronger absorption effect of metal sulphides for polysulfides and the smooth trapping-diffusion-conversion effect of p-SnS/n-SnS2 heterostructure for polysulfides. As a conductive carrier for the growth of vertical 2D p-SnS/n-SnS2 heterostructure nanosheets, rGO can protect the steadiness and enhance the cycle stability of electrode, compared with heterostructure without rGO. In addition, the built-in electric field in the 2D p-SnS/n-SnS2 heterostructure during the discharge/charge processes can effectively accelerate charge transfer, and the charge transfer mechanism in SnS-SnS2 heterostructure during cycling has been investigated. At a rate capability of 2C, the designed SnS-SnS2@rGO as Li-S cathode delivers high specific capacities of 907 mAh g-1 and 571 mAh g-1 after the first cycle and 500 cycles, respectively, which shown excellent cycling ability.

Tunable valley polarization in Janus WSSe by magnetic proximity coupling to a CrI3 layer.

We investigate the electronic properties and valley physics of Janus monolayer WSSe on a CrI3 substrate layer based on first-principles calculations. It is shown that the K and K' valley degeneracy can be lifted which leads to valley polarization (VP) in the WSSe due to the magnetic proximity coupling to a magnetic substrate. The magnitude of VP is highly sensitive to the interfacial electronic properties and can be tuned by varying the stacking configurations of the heterostructure. Interestingly, the direction of VP can be altered by manipulating the layer alignment without reversing the magnetism orientation of the magnetic substrate CrI3. We suggest that the hybridization between the bands of WSSe and the substrate plays an important role. Meanwhile, the charge distributions have been mapped out to uncover the microscopic origin of the direction variable VP. In addition, large VP can be achieved by adjusting the interlayer spacing. Our investigations may have potential applications in the design of valleytronic devices.

Luteolin attenuates cancer cell stemness in PTX-resistant oesophageal cancer cells through mediating SOX2 protein stability.

Cancer drug resistance is a formidable obstacle that enhances cancer stem-like cell properties, tumour metastasis and relapse. Luteolin (Lut) is a natural flavonoid with strong antitumor effects. However, the underlying mechanism(s) by which Lut protects against paclitaxel-resistant (PTX-resistant) cancer cell remains unknown. Herein, we found that Lut significantly attenuated the stem-like properties of PTX-resistant cancer cells by downregulating the expression of SOX2 protein. Additionally, further study showed that Lut could inhibit the PI3K/AKT pathway to decrease the phosphorylation level of AKT(S473) and UBR5 expression, which is an ubiquitin E3 ligase that promotes SOX2 degradation. In addition, Lut also inhibited PTX-resistant cancer cell migration and invasion by blocking epithelial-mesenchymal transition (EMT). Importantly, Lut inhibited the tumorigenic ability of oesophageal PTX-resistant cancer cells and showed no obvious toxicity in vivo. Thus, Lut has potential as a promising agent for drug-resistant oesophageal cancer therapy.

Luteolin combined with low-dose paclitaxel synergistically inhibits epithelial-mesenchymal transition and induces cell apoptosis on esophageal carcinoma in vitro and in vivo.

Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial-mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo. The molecular mechanism of inhibiting cell migration and EMT processes may be related to the inhibition of SIRT1, and the mechanism of apoptosis induction is associated with the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway-mediated activation of mitochondrial apoptotic pathway.

EMT and Cancer Cell Stemness Associated With Chemotherapeutic Resistance in Esophageal Cancer.

Drug resistance often occurs after chemotherapy in esophageal cancer patients, leading to cancer metastasis and recurrence. However, the relationship among cancer cell migration, recurrence and drug resistance in esophageal cancer drug-resistant cells has not been clearly explained. In this study, we constructed paclitaxel (PTX)-resistant esophageal cancer cells to explore the causes of drug resistance and poor prognosis after chemotherapy in esophageal cancer. Colony formation assay was used to evaluate the difference of colony formation between parental cells and drug resistance cells. Microsphere formation assay was used to examine the phenotype of stem cells. Wound healing and Transwell assays were used to detect the migration ability of drug-resistant cells. Western blotting and immunofluorescence assays were used to explore the mechanisms. Finally, we used nude mouse xenograft model to explore the tumor characteristics and the expression of relative proteins to verify our findings in vivo. Our study demonstrated that the cancer cell stemness characteristics exist in drug-resistant esophageal cancer cells, that expressed the biomarkers of stem cells and were prone to epithelial-mesenchymal transition (EMT). Our results suggested that the expression of EMT biomarkers and stemness-related proteins increased in esophageal cancer cells after continuously using chemotherapeutic drugs for a period of time. This study indicated that simultaneously targeting EMT and stemness could be a better strategy for the treatment of esophageal cancer drug resistance.

Cognitive Behavioral Therapy for Autism Spectrum Disorders: A Systematic Review.

CONTEXT: In several studies, authors have reported on cognitive behavioral therapy (CBT) for children and adolescents with autism spectrum disorders (ASDs), but inconsistent treatment effectiveness was revealed from these studies. OBJECTIVE: To evaluate the effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD by using a meta-analytic approach. DATA SOURCES: Data sources included PubMed, Embase, and the Cochrane Library. STUDY SELECTION: We selected randomized controlled trials (RCTs) in which authors reported effectiveness of CBT on the symptoms of ASD and social-emotional problems in children or adolescents with ASD from database inception to May 2019. DATA EXTRACTION: For each study, 2 authors extracted data on the first author's surname, publication year, country, sample size, mean age, CBT target, intervention, outcome measurement, follow-up duration, and investigated outcomes. RESULTS: Forty-five RCTs and 6 quasi RCTs of 2485 children and adolescents with ASDs were selected for the final meta-analysis. There was no significant difference between CBT and control for symptoms related to ASD based on self-reported outcomes (standard mean difference: -0.09; 95% confidence interval: -0.42 to 0.24; P = .593), whereas CBT significantly improved the symptoms related to ASD based on informant-reported outcomes, clinician-rated outcomes, and task-based outcomes. Moreover, the pooled standard mean differences indicated that CBT has no significant effect on symptoms of social-emotional problems based on self-reported outcomes. LIMITATIONS: The quality of included studies was low to modest, significant heterogeneity among the included studies for all investigated outcomes was detected, and publication bias was inevitable. CONCLUSIONS: These findings indicate that CBT may significantly improve the symptoms of ASD and social-emotional problems in children or adolescents with ASD.

Lateral position: a friendly surgical position for intramedullary nailing of tibial shaft fractures via infrapatellar approach.

BACKGROUND: The conventional infrapatellar approach to intramedullary nailing of tibial fractures adopts the supine high-flexion knee position. However, this has disadvantages including difficulty in obtaining the proximal tibial anteroposterior view during intraoperative fluoroscopy, prolonged duration of fluoroscopy. Accordingly, the present study investigated the utility of the lateral position in the infrapatellar approach to intramedullary nailing of tibial shaft fractures. METHODS: The present study was a retrospective analysis of 112 patients who sustained closed tibial shaft fractures and treated with intramedullary nailing via the infrapatellar approach. Patients were divided into two groups according to surgical position: lateral or supine. The demographic and clinical data were collected and analyzed. RESULTS: There were 54 patients in the lateral and 58 in the supine position groups. The duration of surgery and fluoroscopy was shorter in the lateral group than the supine group (p < 0.05). Blood loss during surgery was lower in the lateral compared with supine position group (p < 0.05). The malunion rate was lower in the lateral position group as compared with the supine position group (p < 0.05); moreover, fewer surgical assistants were needed than in the supine group (p < 0.05). There were no significant differences in fracture healing time, other complications between the two groups (p > 0.05). CONCLUSIONS: The lateral position was a more convenient choice for intramedullary nailing of tibial shaft fractures via infrapatellar approach.

Prenatal exposure to air pollutants and early childhood growth trajectories: A population-based prospective birth cohort study.

BACKGROUND: Air pollution exposure during pregnancy has been documented to be associated with impaired fetal growth and adverse birth outcomes, but the evidence regarding the effects of air pollution on early childhood growth is still limited. OBJECTIVE: We aimed to explore the associations of exposure to air pollutants during pregnancy with childhood growth trajectories from birth to age of 6 years. METHODS: A prospective cohort study based on the administrative registration system was conducted covering 62,540 births in Wuhan, China between January 1, 2011 and December 31, 2013 and followed for 6 years. Inverse distance weighted method was used to estimate the concentrations of air pollutants exposure for pregnant women. Group-based trajectory models (GBTM) were used to identify growth patterns of children: slow growth, normal growth, and rapid growth. Multinomial logistic regression models were used to examine the associations between prenatal exposure to air pollutants and childhood growth trajectories with adjustment for maternal age, educational status, pre-pregnancy BMI, residential areas, gestational diabetes, birth type, gender of infant, and breastfeeding duration. RESULTS: The mean (SD) of prenatal exposure concentrations for PM10, SO2, NO2, CO, and O3 were 107.9 (30.4), 32.8(12.6), 55.8(13.1), 1081.2(293.1), and 81.6(31.0) µg/m3 respectively. Compared with normal growth trajectory, increased PM10 and CO exposure were significantly associated with higher risk of slow growth trajectory but lower risk of rapid growth trajectory. An increase in prenatal exposure to NO2 significantly increased both the risk of slow growth trajectory and rapid growth trajectory. Increased prenatal SO2 exposure was significantly associated with rapid growth trajectory and was not associated with low growth trajectory. With O3 exposure levels increased, risk to be rapid growth trajectory decreased. Prenatal air pollutants exposure had a greater impact on childhood growth of children who were girls, and those mothers lived in rural areas and were normal weight before pregnancy. CONCLUSIONS: High levels of air pollutants exposure during pregnancy were associated with the risk of being in a trajectory with the deviation of BMI gain from birth to 6 years old. These findings suggest that efforts to identify children at risk of growth deviation in early childhood should pay attention to environmental exposure during pregnancy for their mothers.

Synthesis and in vitro and in vivo biological evaluation of novel derivatives of flexicaulin A as antiproliferative agents.

As our research focuses on anticancer drugs, a series of novel derivatives of flexicaulin A (FA), an ent-kaurene diterpene, condensed with an aromatic ring were synthesized, and their antiproliferative activities against four human cancer cell lines (TE-1, EC109, MCF-7, and MGC-803) were evaluated. The activities of most of the new compounds were better than those of FA. Compound 2y exhibited the best activity with an IC50 value reaching 0.13 µM against oesophageal cancer cells (EC109 cells). The IC50 values for 2y in normal cells (GES-1 cells and HUVECs) were 0.52 µM and 0.49 µM, respectively. Subsequent mechanistic investigations found that compound 2y can inhibit the proliferation of cancer cells and cell cloning. In addition, 2y could reduce the mitochondrial membrane potential, increase the apoptosis rate, and increase the ROS level in EC109 cells. Moreover, 2y can upregulate the expression of ROS/JNK pathway-related proteins (p-ASK1, p-MKK4, p-JNK, and p-Cjun (ser63)) and pro-apoptotic proteins (Bax, Bad, and Bim). In vivo experiments showed that 2y can inhibit tumour growth in nude mice. The mechanism involves an increase in protein expression in the ROS pathway, leading to changes in apoptosis-related proteins. In addition, compound 2y shows low toxicity. These results indicate that compound 2y holds promising potential as an antiproliferative agent.

Identifying critical exposure windows for ambient air pollution and semen quality in Chinese men.

Emerging studies documented the association between ambient air pollution exposure and semen quality, but the critical exposure windows have not been comprehensively studied. To identify susceptible windows for associations of exposure to ambient respirable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) with sperm concentration, sperm count, total motility, and progressive motility, we recruited 1061 men attending an infertility clinic in Wuhan, China, between 2011 and 2013. We used a distributed lag multivariate linear regression to assess the exposure-lag-response relationship between semen quality and weekly air pollution exposure. The critical exposure windows were during the 6th to 12th sperm development weeks for PM10, 10th to 11th weeks for O3, and 0 to 5th weeks for SO2. Over the entire 12 weeks of spermatogenesis period, an interquartile range increase (IQR) increase in PM10 was associated with declined sperm concentration [-45.64% (95% CI: -59.97%, -26.18%) percent decrease], declined sperm count [-49.42% (95% CI: -64.42%, -28.09%) percent decrease], reduced total motility [-12.42 (95% CI: -20.47, -4.37)], and reduced progressive motility [-8.81 (95% CI: -16.00, -1.61)], SO2 per IQR increase was associated with reduced sperm concentration [-39.73% (95% CI: -55.96%, -17.51%) percent decrease] and total motility [-8.64 (95% CI: -16.90, -0.38)], but NO2 and O3 were not associated with any of the four sperm quality parameters. Our findings suggest that exposure to PM10 during spermatidogenesis period, exposure to SO2 during spermatocytogenesis period, and exposure to O3 during spermiogenesis period were associated with impaired semen quality, which implies air pollutants impair semen quality through varied pathways.

Menopause and frailty: a scoping review.

IMPORTANCE AND OBJECTIVE: Frailty refers to the decline in physiological reserve capacity caused by the deterioration of multiple physiological systems (brain, endocrine system, immune system, and skeletal muscle), leading to increased vulnerability and decreased stress capacity. Women have a higher prevalence of frailty than men, although the epidemiological factors underlying this phenomenon are not fully understood. Menopause and menopause-related characteristics may be among the contributing factors. Hence, the purpose of this scoping review was to explore the relationship between menopause and frailty. We attempted to summarize information such as the age that menopause occurs, years since menopause, types of menopause, and hormones and inflammatory markers of frailty among postmenopausal women. METHODS: PubMed, EMBASE, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature and Web of Science, the China National Knowledge Infrastructure, the China Biomedical Literature Service System, Wanfang Database and the WeiPu (VIP) Database were searched from inception until April 3, 2019. Supplementary searches of the references, cited documents, and similar documents of the included literature were also carried out. DISCUSSION AND CONCLUSIONS: Of 762 papers identified, 15 articles matching the criteria were included. The prevalence of frailty among postmenopausal women ranged from 5.9% to 57.3%. Existing studies suggest that menopause is associated with frailty. Early menopause, hysterectomy, low-free testosterone levels, and high C-reactive protein levels may increase the likelihood of frailty among postmenopausal women. Few original studies have explored the relationship between estrogen and frailty and the results of these studies are conflicting. Changes in hormone and inflammatory cytokine levels may mediate frailty among postmenopausal women. More in-depth research would be required to better understand the physiological and etiological mechanisms of the occurrence of frailty among postmenopausal women.

Symmetric Sodium-Ion Battery Based on Dual-Electron Reactions of NASICON-Structured Na3MnTi(PO4)3 Material.

Symmetric sodium-ion batteries possess promising features such as low cost, easy manufacturing process, and facile recycling post-process, which are suitable for the application of large-scale stationary energy storage. Herein, we proposed a symmetric sodium-ion battery based on dual-electron reactions of a NASICON-structured Na3MnTi(PO4)3 material. The Na3MnTi(PO4)3 electrode can deliver a stable capacity of up to 160 mAh g-1 with a Coulombic efficiency of 97% at 0.1 C by utilizing the redox reactions of Ti3+/4+, Mn2+/3+, and Mn3+/4+. This is the first time to investigate the symmetric sodium-ion full cell using Na3MnTi(PO4)3 as both cathode and anode in the organic electrolyte, demonstrating excellent reversibility and cycling performance with voltage plateaus of about 1.4 and 1.9 V. The full cell exhibits a reversible capacity of 75 mAh g-1 at 0.1 C and an energy density of 52 Wh kg-1. In addition, both ex situ X-ray diffraction (XRD) analysis and first-principles calculations are employed to investigate the sodiation mechanism and structural evolution. The current research provides a feasible strategy for the symmetric sodium-ion batteries to achieve high energy density.