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To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities.By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search.Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively.The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.

Peroxisomal proliferator-activated receptors (PPARs) and microRNAs (miRNAs) play important roles in the development of fetuses, whereas expression changes of PPARs and three miRNAs (miR-17, miR-27b and miR-34a) and whether these miRNAs regulate PPARs in non-GDM macrosomia placenta is unclear.A case-control study was performed to collect information and placental tissues on mothers and newborns of non-GDM macrosomia and normal-birth-weight infants. In vitro HTR8-SVneo cellular model was used to detect the effects of miRNAs on PPARs expression. Quantitative real-time PCR (qRT-PCR) and western blot was applied to examine the expression levels of PPARs, miR-17, miR-27b, and miR-34a in placental tissues and cells.The PPARα/γ mRNA and protein levels were significantly up-regulated and miR-27b was down-regulated in the placenta of macrosomia group compared with in the control group, while no difference was observed in PPARβ, miR-17, and miR-34a. After adjusting for confounding factors, low miR-27b and high PPARα/γ mRNA expression still increased the risk of macrosomia. The PPARα/γ protein levels presented a corresponding decrease or increase when cells were transfected with miR-27b mimic or inhibitor.Placental PPARα/γ and miR-27b expression were associated with non-GDM macrosomia and miR-27b probably promotes the occurrence of non-GDM macrosomia by regulating PPARα/γ protein.Low miR-27b and high PPARα/γ mRNA expression in the placenta were associated with higher risk of macrosomia. In vitro HTR8-SVneo cell experiment supported that miR-27b could negatively regulate the expression of PPARα and PPARγ protein. MiR-27b was probably involved in non-GDM macrosomia through negative regulation of PPARα/γ protein.

ObjectiveMultidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) that is closely associated with clinical outcome. This study scrutinises the transcriptional regulation of MRP2 under different pathophysiological conditions.DesignHepatic MRP2, farnesoid X receptor (FXR) and Forkhead box A2 (FOXA2) expression and clinicopathologic associations were examined by immunohistochemistry in 14 patients with cirrhosis and 22 patients with ALF. MRP2 regulatory mechanisms were investigated in primary hepatocytes,Fxr−/−mice and lipopolysaccharide (LPS)-treated mice.ResultsPhysiologically, homeostatic MRP2 transcription is mediated by the nuclear receptor FXR/retinoid X receptor complex.Fxr−/−mice lack apical MRP2 expression and rapidly progress into hyperbilirubinaemia. In patients with ALF, hepatic FXR expression is undetectable, however, patients without infection maintain apical MRP2 expression and do not suffer from hyperbilirubinaemia. These patients express FOXA2 in hepatocytes. FOXA2 upregulates MRP2 transcription through binding to its promoter. Physiologically, nuclear FOXA2 translocation is inhibited by insulin. In ALF, high levels of glucagon and tumour necrosis factor α induce FOXA2 expression and nuclear translocation in hepatocytes. Impressively, ALF patients with sepsis express low levels of FOXA2, lose MRP2 expression and develop severe hyperbilirubinaemia. In this case, LPS inhibits FXR expression, induces FOXA2 nuclear exclusion and thus abrogates the compensatory MRP2 upregulation. In bothFxr−/−and LPS-treated mice, ectopic FOXA2 expression restored apical MRP2 expression and normalised serum bilirubin levels.ConclusionFOXA2 replaces FXR to maintain MRP2 expression in ALF without sepsis. Ectopic FOXA2 expression to maintain MRP2 represents a potential strategy to prevent hyperbilirubinaemia in septic ALF.

Prenatal exposure to ambient air pollution has been associated with adverse perinatal outcomes in previous studies. However, few studies have examined the interaction between air pollution and the season of conception on term low birth weight (TLBW) or macrosomia. Birth registry data of singleton live births in Wenzhou, China, between January 2015 and December 2016 were accessed from the Wenzhou Maternal and Child Health Information Management platform, and data on the ambient air pollutants in Wenzhou were obtained from the Chinese Air Quality Online Monitoring and Analysis Platform. Single-/two-pollutant binary logistic regression models were used to assess the associations between ambient air pollutants (PM

It is emerging that autophagy-related proteins regulate the adaptive response to DNA damage in maintaining genome stability at multiple pathways. Here, we discuss recent insights into how autophagy-related proteins participate in DNA damage repair processes, influence chromosomal instability, and regulate the cell cycle through autophagy-dependent and independent actions. There is increasing awareness of the importance of these pathways mediated by autophagy-related proteins to DNA damage response (DDR), and disturbances in these regulatory connections may be linked to genomic instability participated in various human diseases, such as cancer and aging.

In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post‐translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2‐induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle–related and apoptosis‐related genes in cisplatin‐stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1‐mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.

Abnormal cognitive aging in older adults is a growing public health problem. Previous studies showed inconsistent results pertaining to the effects of leisure activities on cognitive function in older adults. We conducted a systematic review and meta-analysis of published observational longitudinal studies to examine and synthesize the effects of leisure activities on cognitive function in older adults. MEDLINE, PubMed, EMBASE, PsycINFO (Ovid), CINAHL (EBSCO), and Web of Science databases were searched from January 2012 to January 2022. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Most studies found that leisure activities had a positive effect on cognitive function in older adults. The pooled RR for the effect of leisure activity on cognitive function was 0.77 (95% CI: 0.72–0.81, p p = 0.01). Moreover, studies conducted in European and American countries had significantly lower RR (p = 0.019), compared with those conducted in Asian countries. Our study revealed different effects of various types of leisure activities on different cognitive statuses in older adults. To make innovative recommendations for promoting cognitive function in older adults, more detailed observational longitudinal studies investigating the effects of different types of leisure activities on different cognitive statuses in older adults are needed.

The impact of selenium (Se) on human thyroid function remains unclear, with inconsistent results from recent epidemiological studies. Moreover, the observed associations are prone to bias due to the potential confounding and reverse causation. Mendelian randomization (MR) analysis facilitates the large minimization of biases produced by environmental and lifestyle influences, providing unconfounded estimates of causal effects using instrumental variables. We aim to examine the association between Se concentrations and human thyroid function using a 2-sample MR analysis.Genetic instruments for Se concentrations, including toenail and blood (TAB) and blood Se concentrations, were identified from a genome-wide association study (GWAS) of blood Se (n = 5,477) and toenail Se levels (n = 4,162). GWAS summary statistics on thyroid phenotypes were downloaded from the ThyroidOmics consortium, including thyroid-stimulating hormone (TSH) (n=54,288), free thyroxin (FT4) (n=49,269), hypo (n=53,423), and hyperthyroidism (n=51,823). The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with the weighted median and the mode-based method.Genetically determined TAB Se was negatively associated with FT4 (β = -0.067; 95% CI= -0.106, -0.028; P = 0.001) using the IVW analyses, as well in the additional analyses using the weighted median and weighted-mode methods. No evidence in heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms was detected (all P0.05). Suggestive casual association between increased genetically determined TAB Se concentrations and decreased hypothyroidism risk was found by the IVW method (odds ratio [OR] = 0.847; 95% confidence interval [CI] = 0.728, 0.985; P = 0.031). The causal effect of TAB Se on FT4 was observed in women (β = -0.076; 95% CI= -0.129, -0.024; P = 0.004). However, the influence of genetically determined higher Se concentrations on TSH levels and hyperthyroidism revealed insignificance in the primary and sensitivity analyses.The present MR study indicated that high Se concentration enable the decreasing of FT4 levels, and the effects of Se concentrations on FT4 remain sex-specific. This article is protected by copyright. All rights reserved.

SARS-CoV-2 Omicron has become the predominant variant globally. Current infection models are limited by the need for large datasets or calibration to specific contexts, making them difficult to cater for different settings. To ensure public health decision-makers can easily consider different public health interventions (PHIs) over a wide range of scenarios, we propose a generalized multinomial probabilistic model of airborne infection to systematically capture group characteristics, epidemiology, viral loads, social activities, environmental conditions, and PHIs, with assumptions made on social distancing and contact duration, and estimate infectivity over short time-span group gatherings. This study is related to our 2021 work published in Nature Scientific Reports that modelled airborne SARS-CoV-2 infection (Han, Lam, Li, et al., 2021).1It is differentiated from former works on probabilistic infection modelling in terms of the following: (1) predicting new cases arising from more than one infectious in a gathering, (2) incorporating additional key infection factors, and (3) evaluating the effectiveness of multiple PHIs on SARS-CoV-2 infection simultaneously. Although our results reveal that limiting group size has an impact on infection, improving ventilation has a much greater positive health impact. Our model is versatile and can flexibly accommodate other scenarios by allowing new factors to be added, to support public health decision-making.

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare endocrine disease characterized by gonadal dysplasia. According to whether the sense of smell is affected, this disorder is classified into Kallmann syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (nIHH). In this study, we reported a case of nIHH patient and explored the pathogenic mechanism of FGFR1 in nIHH. A FGFR1 variant (c.2008GA, p.E670K) and a CEP290 variant (c.964GA, p.D322N) were detected by the whole exome sequencing in this nIHH patient. Bioinformatic analysis revealed that this FGFR1 variant (c.2008GA) causes structural perturbations in TK2 domain demonstrating that this variant result in FGFR1 loss-of-function and abnormal signaling. The identification of an additional CEP290 variant (c.964GA) indicated that CEP290 might play a potential role in developmental abnormalities and inhibition of GnRH neuron release. A protein interaction network analysis showed that CEP290 was predicted to interact with FGFR1. In summary, our study identified the potential pathogenic mechanism(s) of the novel FGFR1 variant and indicated that CEP290 might play a role in the GnRH neuron migration route. Our findings expand the mutation spectrum of FGFR1 and CEP290 and provide a reference for clinical diagnosis and treatment of IHH.特发性低促性腺激素性性腺功能减退症(idiopathic hypogonadotropic hypogonadism, IHH)是由于促性腺激素释放激素(gonadotropin-releasing hormone, GnRH)缺乏或作用缺陷引起以性腺发育不良为特征的内分泌罕见病。依据是否并发嗅觉障碍可以分为嗅觉正常特发性低促性腺激素性性腺功能减退症(normosmic isolated hypogonadotropic hypogonadism, nIHH)和嗅觉障碍的卡尔曼综合征(Kallmann syndrome, KS)。本研究收集并分析了1例nIHH散发病例的临床资料。全外显子测序证实患儿同时携带FGFR1基因变异(c.2008GA, p.E670K)和遗传于其母亲的CEP290基因变异(c.964GA, p.D322N)。生物信息学分析发现FGFR1基因突变(c.2008GA)改变FGFR1蛋白TK2结构域,影响FGFR1受体的功能及下游细胞信号转导通路的激活。CEP290基因(c.964GA)可能影响GnRH神经元的正确迁徙途径导致IHH,CEP290蛋白与FGFR1蛋白之间存在相互作用。本研究结果扩展了IHH致病基因表达谱,为探究IHH的致病机制提供了新的方向,并为该类疾病的临床精准诊疗提供了借鉴和参考。.

Based on data from 839 comparable sections (sites) of the national surface water environmental quality monitoring network from 2012 to 2020, the variation tendency of surface water environmental quality over the past nine years was analyzed. The results showed that the environmental quality of surface water in China has continuously improved, the proportion of Grade Ⅰ-Ⅲ water quality increased steadily, and the proportion of inferior Grade Ⅴ water quality decreased in succession. The annual average concentration of ammonia nitrogen, total phosphorus, and permanganate index all showed a decreasing trend annually; compared with those in 2012, the three indicator concentrations respectively declined 75.9%, 48.2%, and 17.5% by 2020. In Guangxi, Hainan, and Ningxia, the proportion of Grade Ⅰ-Ⅲ water quality sections was maintained at 100%, whereas Hubei and Jiangxi showed a consecutive decreasing trend, and the other provinces showed a consecutive increasing trend. In Guangxi, Hainan, Ningxia, Hunan, and Fujian, the proportion of inferior Grade Ⅴ water quality sections remained at 0, and the other provinces showed a decreasing trend yearly. The annual average concentration of total phosphorus in Guangxi and Jiangxi and the permanganate index in Hubei, Hainan, and Liaoning increased annually, whereas that in the other provinces decreased to varying degrees. The proportion of Grade Ⅰ-Ⅲ water quality sections in Ten Major basins showed a fluctuating upward trend. The proportion of inferior Grade Ⅴ water quality in the Zhejiang and Fujian Slice Rivers was maintained at 0, and the other river basins showed a fluctuating and declining trend. The annual average of the main pollution indicators all decreased to varying degrees. In 2020, 53% of 32 important lakes were eutrophic, which increased 12% compared to that in 2012. On the whole, surface water quality has generally improved in China during the past nine years; especially since the 13

Low-dimensional ferroelectricity and polar materials have attracted considerable attentions for their fascinating physics and potential applications. Based on first-principles calculations, here we investigate the stacking modes and polar properties of a typical series of quasi-one-dimensional ferroelectrics: double-chain oxyhalides NbO$X_3$ ($X$=Cl, Br, I). The geometry of their double-chains allows both the interchain/intrachain permutation. Thus, different stacking modes of double-chains lead to a variety of ferroelectric and antiferroelectric phases in both the tetragonal and monoclinic crystals. The proximate energies of these phases may lead to multiphase coexistence in real materials, as well as the hydrostatic pressure driving structural phase transition. Their spontaneous polarizations and piezoelectricity of the ferroelectric phases are prominent, comparable to commercially used ferroelectric BaTiO$_3$ and piezoelectric ZnO, respectively. Our work demonstrates that the van der Waals NbO$X_3$ are promising materials for exploring quasi-one-dimensional ferroelectricity and antiferroelectricity., Comment: 7 pages, 5 figures

Background Evidence suggests that pediatric tuina, which is a modality of traditional Chinese medicine (TCM), might have beneficial effects on attention deficit hyperactivity disorder (ADHD) symptoms. Therefore, we designed and conducted a pilot randomized controlled trial (RCT) on parent-administered pediatric tuina for ADHD in preschool children. This paper reported focus group interview data as a part of a process evaluation embedded with the outcome evaluation of the RCT. To understand the parents’ facilitators and barriers of delivering pediatric tuina to their children with ADHD symptoms. Methods Purposive sampling were employed to invite 15 parents who attended our pediatric tuina training program to voluntarily participate in three focus group interviews. The interviews were audio-recorded and transcribed verbatim. The data was analyzed with template analysis. Results Two themes were identified. Under the theme of the facilitators to the intervention implementation, subthemes included (a) perceived benefits on children and parents, (b) acceptability of children and parents, (c) professional supports, and (d) parents’ expectations on long-term effects of the intervention. Under the theme of the intervention implementation barriers, subthemes included (a) limited benefits on children’s inattention symptoms, (b) manipulation management difficulties, and (c) limitations of TCM pattern identification. Conclusion Parents mainly focused on the health effects and safety of pediatric tuina intervention, especially the effects on children’s sleep quality and appetite. Parents could master and conduct the manipulations well if appropriate support and guidance are provided. Besides, parents need long-term support for persisting this intervention.

Background Discovery of early-stage biomarkers is a long-sought goal of Alzheimer’s disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn’t proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology. Results This AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala–Ala–Asn–Cys–Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg−1, p.o.) reduced production of β-amyloid (Aβ) and ameliorated memory loss. Therefore, elevation of AEP is an early sign of AD onset. Finally, we showed that live animal imaging with this AEP-responsive probe could monitor the up-regulated AEP in the brain of APP/PS1 mice. Conclusions The current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD. Graphical abstract

Reactive oxygen species (ROS) are generally small, short-lived and highly reactive molecules, initially thought to be a pathological role in the cell. A growing amount of evidence in recent years argues for ROS functioning as a signaling intermediate to facilitate cellular adaptation in response to pathophysiological stress through the regulation of autophagy. Autophagy is an essential cellular process that plays a crucial role in recycling cellular components and damaged organelles to eliminate sources of ROS in response to various stress conditions. A large number of studies have shown that DNA damage response (DDR) transducer ataxia-telangiectasia mutated (ATM) protein can also be activated by ROS, and its downstream signaling pathway is involved in autophagy regulation. This review aims at providing novel insight into the regulatory mechanism of ATM activated by ROS and its molecular basis for inducing autophagy, and revealing a new function that ATM can not only maintain genome homeostasis in the nucleus, but also as a ROS sensor trigger autophagy to maintain cellular homeostasis in the cytoplasm.

Background The COVID-19 pandemic and relevant prevention and control measures may affect the mental health and induce depressive symptoms in fathers with concurrent partner delivery exposure. This study aims to investigate the prevalence of depression in fathers with simultaneous exposure to COVID-19 pandemic and the effects of family functions on paternal perinatal depression (PPD) risk. Methods A cross-sectional study was conducted among the perinatal fathers recruited in a large tertiary hospital in Wuhan across the whole pandemic period from 31 December 2019 to 11 April 2020. Edinburgh Postnatal Depression Scale (EPDS) and APGAR family function scale were used to evaluate PPD and family function, respectively. Chi-square test and multivariable-adjusted logistic regression model were applied for data analysis. Results Among the 1187 participants, the prevalence of PPD was 13.82% throughout the COVID-19 pandemic. Compared with that in the time period before the announcement of human-to-human transmission on 19 January 2020, the depression risk was significantly lower during the traffic restriction (OR = 0.54, 95% CI: 0.34, 0.86) and public transportation reopening periods (OR = 0.29, 95% CI: 0.14, 0.59). Poor/fair family functions was associated with elevated depression risk (OR = 2.93, 95% CI: 1.90, 4.52). Individuals reporting a low family income and smoking had high depression risks. Conclusions A declined risk of PPD was observed over the traffic restriction period of the COVID-19 pandemic. An improved family function may help alleviate the risk of PPD during the pandemic. Health authorities are recommended to formulate targeted prevention and control strategies to handle PPD.

Oral antiseizure medications are the preferred option for the clinical treatment of epilepsy. Therapeutic drug monitoring has become an important means of achieving individualized treatment of epilepsy. A sensitive, accurate and rapid LC-ESI-MS/MS method was developed and validated for the simultaneous determination of 15 antiseizure medications in human plasma (carbamazepine, gabapentin, pregabalin, phenytoin, zonisamide, oxcarbazepine, tiagabine, lamotrigine, topiramate, phenobarbital, lacosamide, primidone, 10,11-Dihydro-10-hydroxy carbamazepine, ethosuximide, and levetiracetam). The sample preparation procedure was an one-step protein precipitation with methanol. Mass detection was performed in ionization polarity switching mode (positive-negative-positive) using multiple reaction monitoring mode. A "boot-shaped" gradient elution program was applied to separate and concentrate those target analytes, resulting in symmetrical peak shapes within 10 min, without endogenous interference. The method showed great linearity over the concentration ranges with acceptable correlation coefficients (0.9966-0.9996). The precision and accuracy values for intra- and inter-assays were within ±15%. Consequently, the method was successfully implemented on pediatric patients undergoing mono- or polytherapy for epilepsy and provided timely concentration results to ordering clinicians.

BackgroundOlder adults with mild cognitive impairment (MCI) have the possibility of reverting to normal cognitive function. Leisure activity engagement (LAE) plays a critical role in the progress of the cognitive function. A better understanding of the dynamic relationship between LAE and MCI reversion would inform the implementation of preclinical dementia interventions. This study aimed to investigate the association between change patterns of LAE and MCI reversion among older adults using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database.Study designLongitudinal population-based study.MethodsOlder adults with MCI at the baseline were enrolled in this study. Information about cognitive function, overall, cognitively stimulating, physically active/demanding, and socially engaged LAE was collected at baseline and follow-up. Adjusted hazard ratios (HRs) for reversion and 95% confidence intervals (CIs) were calculated by Cox hazard models with time as the underlying time metric. We also assessed potential effect modifications by creating a cross-product of the stratifying variable with LAE change patterns in the fully adjusted model.ResultsThe restricted cubic spline showed that the association between LAE change scores and MCI reversion rate was statistically significant and nonlinear (pConclusionsParticipants who maintained the highest LAE had the greatest possibility of MCI reversion. Meanwhile, a higher level of LAE maintenance was associated with the increased possibility of MCI reversion. These results provide a practical message to older adults about how dynamic changes in LAE are associated with improved cognitive function.

Skin sensitization is an important regulatory endpoint associated with allergic contact dermatitis. Recently, several adverse outcome pathway (AOP)-based alternative methods were developed to replace animal testing for evaluating skin sensitizers. The AOP-based assays were further integrated as a two-out-of-three method with good predictivity. However, the acquisition of experimental data is resource-intensive. In contrast, an integrated testing strategy (ITS) capable of maximizing the usage of laboratory data from AOP-based and in silico methods was developed as defined approaches (DAs) to both hazard and potency assessment. There are currently two in silico models, namely Derek Nexus and OECD QSAR Toolbox, evaluated in the OECD Testing Guideline No. 497. Since more advanced machine learning algorithms have been proposed for skin sensitization prediction, it is therefore desirable to evaluate their performance under the ITS framework. This study evaluated the performance of a new ITS DA (ITS-SkinSensPred) adopting a transfer learning-based SkinSensPred model. Results showed that the ITS-SkinSensPred has similar or slightly better performance compared to the other ITS models. SkinSensPred-based ITS is expected to be a promising method for assessing skin sensitization.

Bryophytes have been used in many fields, such as landscaping and soil and water conservation. How-ever, few studies focused on moss regeneration and its influencing factors, which retards the application study. Three common desiccation-tolerant mosses (苔藓植物在园林绿化、水土保持等方面的应用日益增加,目前藓类植物营养繁殖的影响因素鲜见报道,限制了其应用研究。本研究以黄土高原常见的耐干藓(扭口藓、土生对齿藓、短叶对齿藓)为对象,研究了3种藓春、夏、秋、冬季营养繁殖能力(以活力指数表征)差异及其叶绿素、可溶性糖、可溶性蛋白质、丙二醛(MDA)含量等生理指标变化,探索了耐干藓营养繁殖的季节差异与其生理特征之间的关系。结果表明: 1)藓类繁殖具有明显的季节差异,3种藓夏季活力指数均低于其他3个季节,平均较秋、冬、春季分别下降56.1%、48.4%、10.1%;相同季节的活力指数具有明显的年际变化。2)3种藓繁殖能力具有明显的种间差异,以短叶对齿藓最高,扭口藓最低,且后者的繁殖能力季节和年际变化最大。3)3种藓不同季节生理特征差异显著,其中夏季MDA含量高于其他季节,可溶性糖和可溶性蛋白质含量低于其他季节。4)耐干藓的营养繁殖季节变化主要与可溶性糖含量有关。本研究明确了藓类营养繁殖能力随季节变化的规律,指出可溶性糖含量是影响藓类营养繁殖的关键因素,可为藓类植物保护和人工培养提供科学依据。.

Considerable research interest has been attracted to noncollinear magnetic structures for their intriguing physics and promising applications. In this work, based on relativistic density functional theory, we reveal the interesting magnetic order and relevant properties in monolayer RuF$_4$, which can be exfoliated from its bulk phase. Although the spins on Ru ions are almost antiferromagnetically aligned between nearest-neighbors, weak ferromagnetism is generated because of the antisymmetric Dzyaloshinskii-Moriya interaction as well as the single-ion anisotropy. A prominent magneto-optical Kerr effect can be observed for this antiferromagnet, similar to those of regular strong ferromagnets. In addition, a uniaxial strain can induce a ferroelastic switching together with the in-plane rotation of spin direction, giving rise to a strong intrinsic magnetoelasticity. Our work not only suggests an alternative direction for two-dimensional magnetic materials, but also provides hints to future devices based on antiferromagnetic magnetoelastic or magneto-optical materials., 7 pages, 5 figures

Background: GnRHa treatment was established for improving final adult height (FAH) in children presenting with Idiopathic central precocious puberty (ICPP) up to age 8, while several controversies remained for older age groups. The primary objective was to evaluate whether boys diagnosed with ICPP over 9 years of chronological age (CA) could achieve a height benefit from GnRHa treatment.Methods: We retrospectively evaluated the medical records of 23 boys treated for idiopathic central precocious puberty between January 2018 and January 2021 at Jiangsu Children's Medical Center. All patients started treatment with intramuscular depot GnRHa at a dose of 80-100 μg/kg, followed by continuous intramuscular injection every 28 days at a dose of 60-80 μg/kg. The hormonal parameters, bone age/chronological age ratio, FAH, growth velocity (GV), tanner staging and body mass index (BMI) were assessed during the treatment period.Results: After one course of treatment (3 months), the basal FSH and testosterone levels were reduced, while the basal LH value was not significantly changed compared with those before treatment. Furthermore, the mean BA/CA ratio reduction was statistically significant at month 12. The mean PAH following administration of GnRHa after 12 months was statistically improved compared with those at baseline. In addition, the clinical sign of puberty and GV were significantly improved and the BMI remained unchanged as desired at month 12.Conclusions: This analysis highlighted the positive outcome on the decrease in the rate of bone maturation, with a favorable effect on progression of clinical signs of puberty. Furthermore, our study confirmed improved PAH even in the older children at onset of treatment (ages 9-10), emphasizing the importance of personalized treatment in such population.

Pulmonary arterial hypertension (PAH) refers to a rare, progressive disorder that is characterized by occlusive pulmonary vascular remodeling, resulting in increased pulmonary arterial pressure, right-sided heart failure, and eventual death. Emerging evidence from genetic investigations of pediatric-onset PAH highlights the strong genetic basis underpinning PAH, and deleterious variants in multiple genes have been found to cause PAH. Nevertheless, PAH is of substantial genetic heterogeneity, and the genetic defects underlying PAH in the overwhelming majority of cases remain elusive. In this investigation, a consanguineous family suffering from PAH transmitted as an autosomal-dominant trait was identified. Through whole-exome sequencing and bioinformatic analyses as well as Sanger sequencing analyses of the PAH family, a novel heterozygous SOX17 mutation, NM_022454.4: c.379C>T; p. (Gln127*), was found to co-segregate with the disease in the family, with complete penetrance. The nonsense mutation was neither observed in 612 unrelated healthy volunteers nor retrieved in the population genetic databases encompassing the Genome Aggregation Database, the Exome Aggregation Consortium database, and the Single Nucleotide Polymorphism database. Biological analyses using a dual-luciferase reporter assay system revealed that the Gln127*-mutant SOX17 protein lost the ability to transcriptionally activate its target gene NOTCH1. Moreover, the Gln127*-mutant SOX17 protein exhibited no inhibitory effect on the function of CTNNB1-encode β-catenin, which is a key player in vascular morphogenesis. This research firstly links SOX17 loss-of-function mutation to familial PAH, which provides novel insight into the molecular pathogenesis of PAH, suggesting potential implications for genetic and prognostic risk evaluation as well as personalized prophylaxis of the family members affected with PAH.

Improving the storage capacities of electrode materials is one of the most critical points for ion batteries. Two-dimensional (2D) topological semimetals with high carrier mobility are naturally suitable as electrode materials. Herein, using the first-principle calculations, 2D BP monolayer with Dirac-type band structure is predicted to be a superior anode material with ultrahigh capacity for both Li/Na-ion batteries. The BP monolayer remains metallic after the adsorption of Li/Na ions, ensuring a good conductivity. Furthermore, BP owns low diffusion barriers (0.35 eV for Li ions and 0.16 eV for Na ions) and a moderate lattice change (3%) during the process of charging and discharging. Remarkably, the storage capacity of monolayer BP is enhanced to 1924 mAh/g by multilayer adsorption of both Li/Na ions, much higher than those of most previous 2D anode materials. All these characteristics strongly suggest that BP has great potential as a superior anode material in Li/Na-ion batteries.

To explore Chinese late-life immigrants' perceptions of loneliness and social isolation.A qualitative descriptive methodology underpinned this study. In-depth individual interviews were conducted in Mandarin with purposively recruited participants. The twenty-three participants in the study had all emigrated from China, were 65-80 years old on arrival and had lived in New Zealand for between 2.5 and 16 years. An inductive thematic analytic process was undertaken. The COREQ checklist was followed to ensure study rigour.Three themes, 'high value placed on meeting family obligations', 'feeling a deep sense of imbalanced intergenerational reciprocity' and 'moving away from filial expectations', were identified. Confucianist values of 'women's domestic duty of caring for grandchildren', 'filial piety', and 'saving face' to be accepted and respected by others negatively attributed to participants' understandings and experiences of loneliness. To plan for increasing frailty and to avoid family conflict while ameliorating potential loneliness, some participants reluctantly discarded prior customary filial piety expectations in favour of formal aged care options.Participants' profound sense of loneliness was seen to be attributed to their deeply rooted cultural values and backgrounds from having lived for a significant period of time in China. Loneliness occurred as a result of the resettlement process in later life. These experiences highlight the importance of using cultural framing that takes into account beliefs and adaptations to host societies anticipated during the process of late-life immigration.

Traditional corrosion inhibitors make great contribution to metal protection, but also cause environmental pollution. To solve the problem, plant extracts as green corrosion inhibitors have attracted much attention in recent years. Plants are good raw materials for corrosion inhibitors and also meet the requirements of industry. However, they have not been successfully applied in industry due to the unknown composition of the effective corrosion inhibitors and large dosage thereof. Therefore, cinchonain IIa was separated from Uncaria laevigata with abundant sources and low cost from nature in this work. Here we hypothesized that cinchonain IIa could show good corrosion inhibition performance for Q235 steel in the acidic medium. Through experiments and theoretical calculation, we studied the corrosion inhibition effect of cinchonain IIa on Q235 in 1 M HCl solution at 298 K for 48 h. Electrochemical experiments revealed that the inhibition efficiency of 200 mg/L cinchonain IIa in 1 M HCl for Q235 steel was 94.08% for 48 h. It even showed over 93% corrosion inhibition efficiency and durable protection performance to 28 d. Surface observations indicated that cinchonain IIa were firmly attached to the steel surface by forming a protective film. Moreover, quantum chemical calculation and molecular dynamics simulation revealed the inhibition mechanism at molecular and atomic level. Compared with some plant extracts, here we demonstrate that the outstanding advantages of cinchonain IIa include sustained protective effect, small dosage, and low toxicity. Accordingly, it may be used as a green industrial corrosion inhibitor with great potential in oilfield acidification and acid pickling.

Irisin, a myokine mainly secreted by skeletal and cardiac muscles, is actively involved in cardiovascular diseases. However, whether irisin is associated with aortic stenosis remains unknown. Two hundred ninety-three severe AS patients who underwent transcatheter aortic valve implantation were enrolled and followed-up for 35 months on average. Enzyme-linked immunosorbent assay (ELISA) was applied to measure circulating irisin levels. Patients were divided into two groups based on the median plasma irisin level. We found that high plasma irisin levels were independently associated with pure aortic stenosis (PAS) after adjusting for age, body mass index, history of peripheral vascular disease, and creatinine (OR = 3.015, 95% CI 1.775–5.119, P AUC = 0.647, 95% CI 0.583–0.711, P P

In the title compound, [NiCl

Cordyceps cicadae is an entomogenous fungus, which is used as both medicine and food due to the presence of rich bioactive substances. Currently, most studies focus on the pharmacological effects of the bioactive components of C. cicadae, but the research on their processing is still in its infancy. In this study, polysaccharides were extracted from insect-cultivated C. cicadae (tussah pupae C. cicadae and domestic silkworm pupae C. cicadae) and wild C. cicadae. The functional properties of C. cicadae polysaccharides were evaluated. At the same time, the in vitro antioxidant activity of the insect-cultivated C. cicadae was determined and compared with the wild C. cicadae. The results showed that the cultivated C. cicadae polysaccharides and the wild one had similar structures, and both had appreciable water solubility, oilholding capacity, thermal stability, and emulsifying property compared to foaming property and foaming stability. Further, the C. cicadae polysaccharides cultured on silkworm pupae and tussah pupae showed comparable antioxidant and reducing power to the wild C. cicadae. Our data indicates that the C. cicadae polysaccharides have the potential as a food additive, among which the domestic silkworm pupae C. cicadae showed the best outcome, and the C. cicadae polysaccharides cultured by bionic method have the same antioxidant activity as the wild one.

In this work, zinc sulfide (ZnS) on hydroxylated multi-walled carbon nanotubes (MWCNTs) composite was prepared for lithium-ion batteries (LIBs) anode. It is demonstrated that atomic layer deposition (ALD) enables a conformal, uniform, and ultrathin ZnS (~ 7 nm) layer onto the surface of hydroxylated MWCNTs. The resulting MWCNTs@ZnS core–shell composite displays excellent electrochemical performances as LIBs anode, accounting for high capacity, stable cyclability, high rate capability, and exceptional coulombic efficiency. The MWCNTs@ZnS composite can exhibit a stable discharge capacity, sustaining 520 mAh g−1 versus 108 mAh g−1 for commercial ZnS powders after 200 cycles at 100 mA g−1. The improved electrochemical performances are attributed to the synergistic effect from MWCNTs and ALD ZnS film. MWCNTs have good conductivity and huge surface area while the ALD ZnS film has high Li storage capability. This study verifies that ALD is highly flexible in developing excellent electrodes of LIBs.

Background Currently, there is no cure for Alzheimer’s disease (AD). Therapeutics that can modify the early stage of AD are urgently needed. Recent studies have shown that the pathogenesis of AD is closely regulated by an endo/lysosomal asparaginyl endopeptidase (AEP). Inhibition of AEP has been reported to prevent neural degeneration in transgenic mouse models of AD. However, more than 90% of AD cases are age-related sporadic AD rather than hereditary AD. The therapeutic efficacy of AEP inhibition in ageing-associated sporadic AD remains unknown. Methods The senescence-accelerated mouse prone 8 (SAMP8) was chosen as an approximate model of sporadic AD and treated with a selective AEP inhibitor,: δ-secretase inhibitor 11. Activation of AEP was determined by enzymatic activity assay. Concentration of soluble amyloid β (Aβ) in the brain was determined by ELISA. Morris water maze test was performed to assess the learning and memory-related cognitive ability. Pathological changes in the brain were explored by morphological and western blot analyses. Results The enzymatic activity of AEP in the SAMP8 mouse brain was significantly higher than that in the age-matched SAMR1 mice. The half maximal inhibitory concentration (IC50) for δ-secretase inhibitor 11 to inhibit AEP in vitro is was around 150 nM. Chronic treatment with δ-secretase inhibitor 11 markedly decreased the brain AEP activity, reduced the generation of Aβ1–40/42 and ameliorated memory loss. The inhibition of AEP with this reagent not only reduced the AEP-cleaved tau fragments and tau hyperphosphorylation, but also attenuated neuroinflammation in the form of microglial activation. Moreover, treatment with δ-secretase inhibitor 11 prevented the synaptic loss and alleviated dendritic disruption in SAMP8 mouse brain. Conclusions Pharmacological inhibition of AEP can intervene and prevent AD-like pathological progress in the model of sporadic AD. The up-regulated AEP in the brain could be a promising target for early treatment of AD. The δ-secretase inhibitor 11 can be used as a lead compound for translational development of AD treatment.

Two-dimensional topological materials attracted intense interest in condensed matter physics due to their topologically protected edge states and potential applications in electronic devices. Here, based on first-principles calculations, we found that a two-dimensional CX3 (X = Sb, Bi) monolayer is a quantum spin Hall insulator with a large band gap. With the strong spin-orbit coupling effect, CX3 exhibits noticeable bulk band gaps up to 470 meV, sufficiently large for realizing the quantum spin Hall effect at room temperature. The topological characteristic is confirmed by the Z2 invariant since the system preserves time-reversal symmetry. Particularly, the CSb3 monolayer displays unique topologically entangled Rashba-splitting edge states, resembling nearly free-electron quadratic dispersion. Such topologically entangled Rashba-like edge states derive from the spin-orbit coupling effect and inversion symmetry breaking on the edges. Moreover, we demonstrate that the topological properties are perfectly preserved in the CX3 monolayer even with a h-BN substrate. The nontrivial quantum spin Hall state in the CX3 monolayer will provide possibilities for studying a novel phenomenon of edge states and potential applications in low-dissipation electronic devices.

With the rapid development of Internet of Things technology, RFID technology has been widely used in various fields. In order to optimize the RFID system hardware deployment strategy and improve the deployment efficiency, the prediction of the RFID system identification rate has become a new challenge. In this paper, a neighborhood rough set and random forest (NRS-RF) combination model is proposed to predict the identification rate of an RFID system. Firstly, the initial influencing factors of the RFID system identification rate are reduced using neighborhood rough set theory combined with the principle of heuristic attribute reduction of neighborhood weighted dependency, thus obtaining a kernel factor subset. Secondly, a random forest prediction model is established based on the kernel factor subset, and a confusion matrix is established using out-of-bag (OOB) data to evaluate the prediction results. The test is conducted under the constructed RFID experimental environment, whose results showed that the model can predict the identification rate of the RFID system in a fast and efficient way, and the classification accuracy can reach 90.5%. It can effectively guide the hardware deployment and communication parameter protocol setting of the system and improve the system performance. Compared with BP neural network (BPNN) and other prediction models, NRS-RF has shorter prediction time and faster calculation speed. Finally, the validity of the proposed model was verified by the RFID intelligent archives management platform.

The NAC transcription factors play important roles in regulating plant growth, development, and senescence, and responding to biotic and abiotic stressors in plants. A novel coding sequence (1,059 bp) was cloned from hexaploid triticale in this study. The putative protein (352 amino acids) encoded by this sequence was over 95% similar to the amino acid sequence of a NAC protein from