Complete genomic profiles of 1496 Taiwanese reveal curated medical insights.

INTRODUCTION: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population. OBJECTIVES: This study provides comprehensive medical genomic findings from TWB WGS data, for better characterization of disease susceptibility and the choice of ideal treatment regimens in Taiwanese population. METHODS: We reanalyzed 1496 WGS using a PrecisionFDA Truth challenge winner method Sentieon DNAscope. Single nucleotide variants (SNV) and small insertions/deletions (INDEL) were benchmarked. We also analyzed pharmacogenomic (PGx) drug-associated alleles, and copy number variants (CNV). Multiple practicing clinicians reviewed and curated the clinically significant variants. Variant annotations can be browsed at TaiwanGenomes (https://genomes.tw). RESULTS: We found that each participant had an average of 6,870.7 globally novel variants and 75.3% (831/1103) of the participants harbored at least one PharmGKB-selected high evidence level human leukocyte antigen (HLA) risk allele. 54 PharmGKB-reported high-level instances of evidence of Cytochrome P450 variant-drug pairs, with a population frequency of over 13.2%. We also identified 23 variants in the ACMG secondary finding V3 gene list from 25 participants, suggesting that 1.67% (25/1496) of the population is harboring at least one medical actionable variant. Our carrier status analyses suggest that one in 25 couples (3.94%) would risk having offspring with at least one pathogenic variant, which is in line with rates found in Japan and Singapore. For pathogenic CNV, we detected 6.88% and 2.02% carrier rates for alpha thalassemia and spinal muscular atrophy, respectively. CONCLUSION: Our study highlights the overall medical insights of a complete Taiwanese genomic profile.

Regulation of ROS/inflammasome Axis is Essential for Cardiac Regeneration in Aging Rats Receiving Transplantation of Mesenchymal Stem Cells.

BACKGROUND: Aging is a biological and gradual deterioration of function in living organisms. Aging is one of the risk factors for heart disease. OBJECTIVE: Although mesenchymal stem cell transplantation shows potential in heart disease treatment, the relationship between stem cell-based therapy and oxidative stress/inflammasome axis regulation remains unclear. This study hypothesized that intervention of stem cells showed a protective effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome axis. METHODS: An aging animal model was designed to test the above hypothesis. Experimental animals were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose), and D-gal+WJSC (aging rats receiving mesenchymal stem cells). RESULTS: Compared to the Sham, the experimental results indicate that structural alteration (HE stain and Masson's Trichrome stain), oxidative stress elevation (increase of TBARS level, expression of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression of cardiogenesis marker Troponin T, and inflammasome related protein markers expression (NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition, migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group. CONCLUSION: These findings suggest that mesenchymal stem cell transplantation effectively ameliorates aging hearts through oxidative stress/inflammasome axis regulation. The results from this study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.

A novel STAT3/ NFκB p50 axis regulates stromal-KDM2A to promote M2 macrophage-mediated chemoresistance in breast cancer.

BACKGROUND: Lysine Demethylase 2A (KDM2A) plays a crucial role in cancer cell growth, differentiation, metastasis, and the maintenance of cancer stemness. Our previous study found that cancer-secreted IL-6 can upregulate the expression of KDM2A to promote further the transition of cells into cancer-associated fibroblasts (CAFs). However, the molecular mechanism by which breast cancer-secreted IL-6 regulates the expression of KDM2A remains unclear. Therefore, this study aimed to elucidate the underlying molecular mechanism of IL-6 in regulating KDM2A expression in CAFs and KDM2A-mediated paclitaxel resistance in breast cancer. METHODS: The ectopic vector expression and biochemical inhibitor were used to analyze the KDM2A expression regulated by HS-578 T conditioned medium or IL-6 in mammary fibroblasts. Immunoprecipitation and chromatin immunoprecipitation assays were conducted to examine the interaction between STAT3 and NFκB p50. M2 macrophage polarization was assessed by analyzing M2 macrophage-specific markers using flow cytometry and RT-PCR. ESTIMATE algorithm was used to analyze the tumor microenvironment-dominant breast cancer samples from the TCGA database. The correlation between stromal KDM2A and CD163 + M2 macrophages was analyzed using the Pearson correlation coefficient. Cell viability was determined using trypan blue exclusion assay. RESULTS: IL-6 regulates gene expression via activation and dimerization of STAT3 or collaboration of STAT3 and NFκB. However, STAT3, a downstream transcription factor of the IL-6 signaling pathway, was directly complexed with NFκB p50, not NFκB p65, to upregulate the expression of KDM2A in CAFs. Enrichment analysis of immune cells/stromal cells using TCGA-breast cancer RNA-seq data unveiled a positive correlation between stromal KDM2A and the abundance of M2 macrophages. CXCR2-associated chemokines secreted by KDM2A-expressing CAFs stimulated M2 macrophage polarization, which in turn secreted CCL2 to increase paclitaxel resistance in breast cancer cells by activating CCR2 signaling. CONCLUSION: This study revealed the non-canonical molecular mechanism of IL-6 secreted by breast cancer upregulated KDM2A expression in CAFs via a novel STAT3/NFκB p50 axis, which STAT3 complexed with NFκB p50 in NFκB p50 binding motif of KDM2A promoter. KDM2A-expressing CAFs dominantly secreted the CXCR2-associated chemokines to promote M2 macrophage polarization and enhance paclitaxel resistance in breast cancer. These findings underscore the therapeutic potential of targeting the CXCR2 or CCR2 pathway as a novel strategy for paclitaxel-resistant breast cancer.

Clinical features, surgical treatment, and long-term outcomes of moyamoya disease in a single institution of Fujian, Southeast China: A retrospective study.

At present, detailed demographic and clinical data of moyamoya disease (MMD) in the population of Southeast China are lacking. Therefore, this study aimed to evaluate the epidemiological and clinical features of MMD in Southeast China. Our cohort included 170 patients diagnosed with MMD over the preceding 5 years. Clinical characteristics were obtained through a retrospective chart review, while follow-up information and outcomes were obtained through clinical visits and imaging. The median age at symptom onset was 49 years (range 4-73), with a peak in the age distribution observed at 41 to 60 years. The female-to-male ratio was 1.125 (90/80), and the ratio of the ischemic type to the hemorrhagic type was 2.33 (119/50). The most common initial symptom was an ischemic event. The 5-year Kaplan-Meier risk of stroke was 4.9% for all patients treated with surgical revascularization. Of all patients, 83.9% were able to live independently with no significant disability, and 89.8% showed improved cerebral hemodynamics. Our study provided detailed demographic and clinical data on Southeastern Chinese patients with MMD, which was consistent with findings in other parts of China. Raising clinical awareness of MMD in primary hospitals is important to facilitate early diagnosis and timely treatment of MMD patients.

BDE-209-induced genotoxicity, intestinal damage and intestinal microbiota dysbiosis in zebrafish (Danio Rerio).

The environmental presence of polybrominated diphenyl ethers (PBDEs) is ubiquitous due to their wide use as brominated flame retardants in industrial products. As a common congener of PBDEs, decabromodiphenyl ether (BDE-209) can pose a health risk to animals as well as humans. However, to date, few studies have explored BDE-209's toxic effects on the intestinal tract, and its relevant mechanism of toxicity has not been elucidated. In this study, adult male zebrafish were exposed to BDE-209 at 6 µg/L, 60 µg/L and 600 µg/L for 28 days, and intestinal tissue and microbial samples were collected for analysis to reveal the underlying toxic mechanisms. Transcriptome sequencing results demonstrated a dose-dependent pattern of substantial gene differential expression in the group exposed to BDE-209, and the differentially expressed genes were mainly concentrated in pathways related to protein synthesis and processing, redox reaction, and steroid and lipid metabolism. In addition, BDE-209 exposure caused damage to intestinal structure and barrier function, and promoted intestinal oxidative stress, inflammatory response, apoptosis and steroid and lipid metabolism disorders. Mechanistically, BDE-209 induced intestinal inflammation by increasing the levels of TNF-α and IL-1ß and activating the NFκB signaling pathway, and might induce apoptosis through the p53-Bax/Bcl2-Caspase3 pathway. BDE-209 also significantly inhibited the gene expression of rate-limiting enzymes such as Sqle and 3ßhsd (p < 0.05) to inhibit cholesterol synthesis. In addition, BDE-209 induced lipid metabolism disorders through the mTOR/PPARγ/RXRα pathway. 16S rRNA sequencing results showed that BDE-209 stress reduced the richness and diversity of intestinal microbiota, and reduced the abundance of probiotics (e.g., Bifidobacterium and Faecalibacterium). Overall, the results of this study help to clarify the intestinal response mechanism of BDE-209 exposure, and provide a basis for evaluating the health risks of BDE-209 in animals.

Redefine the role of d-α-Tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein, multidrug resistance protein 1, and breast cancer resistance protein mediated cancer multidrug resistance.

Cancer drug resistance is an ever-changing problem that most patients need to face in their later stages of treatment, especially the multidrug resistant (MDR) type. The drug efflux transporters, including P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP), play the crucial roles in this sophisticated battle. In recent decades, researchers try to find potential inhibitors to impede the drug efflux function of above transporters. d-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is a prevalently used excipient in the formulation design. In the present study, the modulatory effects and mechanisms of vitamin E TPGS on the efflux transporters were investigated. And the cancer MDR reversing ability of vitamin E TPGS was evaluated as well. Stable-cloned transporter over-expressed cell lines were used for mechanisms study, while several types of MDR cancer cell lines were adopted as reversing evaluation models. The results exhibited that vitamin E TPGS significantly inhibited the efflux function of P-gp, MRP1, and BCRP under non-cytotoxic concentrations, but not influencing the protein expression levels. Through efflux assay and molecular docking, vitamin E TPGS was found to be an uncompetitive, non-competitive, and competitive inhibitor on chemotherapeutic drug doxorubicin efflux in P-gp, MRP1, and BCRP over-expressing cell lines, respectively. Furthermore, the basal ATPase activity of three transporters were significantly inhibited by vitamin E TPGS at 10 µM. And the cell membrane fluidity of P-gp over-expressing cell line was enhanced by 22.58% with 5 µM vitamin E TPGS treatment, compared to the parental Flp-In™-293 cell line (without P-gp). The resistance reversing ability of vitamin E TPGS was prominent in MCF-7/DOX MDR breast cancer cell line, which over-expressed P-gp, MRP1, and BCRP. These significant results suggested that vitamin E TPGS is a promising modulator on transporters mediated cancer MDR. Vitamin E TPGS is not an inert excipient, but possesses MDR-reversing pharmacological effects, and deserves a re-purposing application on the future combinatorial regimen design for MDR cancer treatment.

Combining body mass index and waist height ratio to assess the relationship between obesity and serum uric acid levels in adolescents.

Background: The study aims to explore the relationship between obesity and serum uric acid in adolescents by combining body mass index and waist height ratio. Methods: 475 adolescents in our study were classified as normal weight without central obesity (NW), normal weight but central obesity (NWCO), overweight or obesity without central obesity (OB) and overweight or obesity with central obesity (OBCO). Odds ratios (OR) and 95% confidence intervals (CI) for hyperuricemia were calculated using a logistic regression model. The dose-response association between obesity indicators and serum uric acid were explored by restricted cubic spline model. Results: The highest serum uric acid level and the OR for hyperuricemia were found in the OBCO group, regardless of sex. After controlling for waist height ratio, the risk of hyperuricemia increased with increasing body mass index in boys and girls. The restricted cubic spline model showed that boys had higher ORs for hyperuricemia at the 25th and 75th percentiles of body mass index than for waist height ratio and girls had a higher OR for hyperuricemia than waist height ratio at the 25th percentile of body mass index. Conclusions: Hyperuricemia in adolescence was not only associated with the overweight or obesity in BMI, but with the combination of overweight or obesity in BMI and central obesity in WHtR. However, in boys and girls, the increased risk of hyperuricemia associated with elevated body mass index was significantly better than that of waist height ratio.

Schisandrin B Protects against Ischemic Brain Damage by Regulating PI3K/AKT Signaling in Rats.

OBJECTIVE: To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats. METHODS: The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored. RESULTS: Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 ß and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01). CONCLUSIONS: Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.

GLP-1R knockdown abrogates the protective effects of liraglutide on ischaemic stroke via inhibition of M2 polarisation and activation of NLRP3 inflammasome by reducing Nrf2 activation.

Liraglutide has been recently discovered to penetrate the blood-brain barrier to exert neuroprotective effects. However, relevant mechanisms of the protective effects of liraglutide on ischaemic stroke remain to be elucidated. This study examined the mechanism of GLP-1R in regulating the protective effect of liraglutide against ischaemic stroke. Middle cerebral artery occlusion (MCAO) male Sprague-Dawley rat model with/without GLP-1R or Nrf2 knockdown was established and subjected to liraglutide treatment. Then neurological deficit and brain oedema of rats was evaluated and brain tissues were subjected to TTC, Nissl, TUNEL and immunofluorescence staining. Rat primary microglial cells firstly underwent lipopolysaccharide (LPS) treatment, then GLP-1R or Nrf2 knockdown treatment, and finally Liraglutide treatment to research the NLRP3 activation. As a result, Liraglutide protected rats' brain tissues after MCAO, which attenuated brain oedema, infarct volume, neurological deficit score, neuronal apoptosis and Iba1 expression but enhanced live neurons. However, GLP-1R knockdown abrogated these protective effects of liraglutide on MCAO rats. According to in vitro experiments, Liraglutide promoted M2 polarisation, activated Nrf2 and inhibited NLRP3 activation in LPS-induced microglial cells, but GLP-1R or Nrf2 knockdown reversed these effects of Liraglutide on LPS-induced microglial cells. Further, Nrf2 knockdown counteracted the protection of liraglutide on MCAO rats, whereas sulforaphane (agonist of Nrf2) counteracted the effect of Nrf2 knockdown on liraglutide-treated MCAO rats. Collectively, GLP-1R knockdown abrogated the protection of liraglutide on MCAO rats by activating NLRP3 via inactivating Nrf2.

Altered adolescents obesity metabolism is associated with hypertension: a UPLC-MS-based untargeted metabolomics study.

Objective: This study aimed to explore the relationship between the plasma metabolites of adolescent obesity and hypertension and whether metabolite alterations had a mediating effort between adolescent obesity and hypertension. Methods: We applied untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to detect the plasma metabolomic profiles of 105 adolescents. All participants were selected randomly based on a previous cross-sectional study. An orthogonal partial least squares- discriminant analysis (OPLS-DA), followed by univariate statistics and enrichment analysis, was used to identify differential metabolites. Using logistic regression for variable selection, an obesity-related metabolite score (OMS, OMS=∑k=1nßnmetabolite n) was constructed from the metabolites identified, and hypertension risk was estimated. Results: In our study, based on P< 0.05, variable importance in projection (VIP) > 1.0, and impact value > 0.1, we identified a total of 12 differential metabolites. Significantly altered metabolic pathways were the sphingolipid metabolism, purine metabolism, pyrimidine metabolism, phospholipid metabolism, steroid hormone biosynthesis, tryptophan, tyrosine, and phenylalanine biosynthesis. The logistic regression selection resulted in a four-metabolite score (thymidine, sphingomyelin (SM) d40:1, 4-hydroxyestradiol, and L-lysinamide), which was positively associated with hypertension risk (odds ratio: 7.79; 95% confidence interval: 2.13, 28.47; for the quintile 4 compared with quartile 1 of OMS) after multivariable adjustment. Conclusions: The OMS constructed from four differential metabolites was used to predict the risk of hypertension in adolescents. These findings could provide sensitive biomarkers for the early recognition of hypertension in adolescents with obesity.

The Application of Reference Dose Prediction Model to Human Health Water Quality Criteria and Risk Assessment.

Oral reference dose (RfD) is a key parameter for deriving the human health ambient water quality criteria (AWQC) for non-carcinogenic substances. In this study, a non-experimental approach was used to calculate the RfD values, which explore the potential correlation between toxicity and physicochemical characteristics and the chemical structure of pesticides. The molecular descriptors of contaminants were calculated using T.E.S.T software from EPA, and a prediction model was developed using a stepwise multiple linear regression (MLR) approaches. Approximately 95% and 85% of the data points differ by less than 10-fold and 5-fold between predicted values and true values, respectively, which improves the efficiency of RfD calculation. The model prediction values have certain reference values in the absence of experimental data, which is beneficial to the advancement of contaminant health risk assessment. In addition, using the prediction model constructed in this manuscript, the RfD values of two pesticide substances in the list of priority pollutants are calculated to derive human health water quality criteria. Furthermore, an initial assessment of the health risk was performed by the quotient value method based on the human health water quality criteria calculated by the prediction model.

Assessment of bypass patency using transcranial Doppler sonography: correlations with computerized tomography angiography findings in patients with moyamoya disease.

To explore the utility of transcranial Doppler (TCD) findings when assessing bypass patency in patients with Moyamoya disease (MMD). Computed tomography angiography (CTA) and TCD sonography (TCDS) were performed before and after surgery to evaluate bypass patency. The peak systolic flow velocity (PSV) of the superficial temporal artery (STA) and the pulsatility index (PI) were compared between the groups that achieved patency and not, and receiver operating characteristic (ROC) curve analyses were used to define the TCDS criteria revealing patency. This study included 35 hemispheres (15 women; mean age 47 years) with Moyamoya disease who underwent STA-middle carotid artery bypass in our institution between January 2022 and October 2022. The PSV first increased on postoperative days 4-5 and then decreased on postoperative days 6-7 and 7-8. Patients with transient neurological diseases (TNDs), compared to those without, evidenced a significantly lower PSV value (P < 0.05). Compared with the non-patency group, the PSV was higher (P < 0.001) in the patency group. The cutoff values reflecting patency with good sensitivity and specificity were PSV > 49.00; PSV ratio (postoperative/preoperative) > 1.218; PSV ratio (operation side/contralateral side) > 1.082; and PSV ratio (adjusted) > 1.202. In the patency group, the PSV and PI significantly increased (P < 0.001) and decreased (P < 0.001) respectively. Bypass patency can be noninvasively and accurately evaluated via TCDS, affording an objective basis for assessment of the effect of revascularization surgery on patients with MMD.

Host defence peptide LEAP2 contributes to antimicrobial activity in a mustache toad (Leptobrachium liui).

BACKGROUND: The liver-expressed antimicrobial peptide 2 (LEAP2) is essential in host immunity against harmful pathogens and is only known to act as an extracellular modulator to regulate embryonic development in amphibians. However, there is a dearth of information on the antimicrobial function of amphibian LEAP2. Hence, a LEAP2 homologue from Leptobrachium liui was identified, characterized, and chemically synthesized, and its antibacterial activities and mechanisms were determined. RESULTS: In this study, LEAP2 gene (Ll-LEAP2) cDNA was cloned and sequenced from the Chong'an Moustache Toad (Leptobrachium liui). The predicted amino acid sequence of Ll-LEAP2 comprises a signal peptide, a mature peptide, and a prodomain. From sequence analysis, it was revealed that Ll-LEAP2 belongs to the cluster of amphibian LEAP2 and displays high similarity to the Tropical Clawed Frog (Xenopus tropicalis)'s LEAP2. Our study revealed that LEAP2 protein was found in different tissues, with the highest concentration in the kidney and liver of L. liui; and Ll-LEAP2 mRNA transcripts were expressed in various tissues with the kidney having the highest mRNA expression level. As a result of Aeromonas hydrophila infection, Ll-LEAP2 underwent a noticeable up-regulation in the skin while it was down-regulated in the intestines. The chemically synthesized Ll-LEAP2 mature peptide was selective in its antimicrobial activity against several in vitro bacteria including both gram-positive and negative bacteria. Additionally, Ll-LEAP2 can kill specific bacteria by disrupting bacterial membrane and hydrolyzing bacterial gDNA. CONCLUSIONS: This study is the first report on the antibacterial activity and mechanism of amphibian LEAP2. With more to uncover, the immunomodulatory functions and wound-healing activities of Ll-LEAP2 holds great potential for future research.

Roles of protein tyrosine phosphatases in hepatocellular carcinoma progression (Review).

Hepatocellular carcinoma (HCC) represents almost 80% of all liver cancers, is the sixth most common cancer and is the second­highest cause of cancer­related deaths worldwide. Protein tyrosine phosphatases (PTPs), which are encoded by the largest family of phosphatase genes, play critical roles in cellular responses and are implicated in various signaling pathways. Moreover, PTPs are dysregulated and involved in various cellular processes in numerous cancers, including HCC. Kinases and phosphatases are coordinators that modulate cell activities and regulate signaling responses. There are multiple interacting signaling networks, and coordination of these signaling networks in response to a stimulus determines the physiological outcome. Numerous issues, such as drug resistance and inflammatory reactions in the tumor microenvironment, are implicated in cancer progression, and the role of PTPs in these processes has not been well elucidated. Therefore, the present review focused on discussing the relationship of PTPs with inflammatory cytokines and chemotherapy/targeted drug resistance, providing detailed information on how PTPs can modulate inflammatory reactions and drug resistance to influence progression in HCC.

Parent-child interactions in early life mediating association between prenatal maternal stress and autistic-like behaviors among preschoolers.

A range of studies have shown that prenatal maternal stress (PNMS) exposure is associated with offspring autistic-like behaviors, however the potential pathways remain unexplored. This study aimed to evaluate the mediating role of parent-child interactions in early life in the association between PNMS exposure and preschoolers' autistic-like behaviors. Data from 65,928 child-parent dyads were obtained via a primary caregiver-reported questionnaire administered as part of the Longhua Child Cohort Study. To strengthen confidence in the reliability of the results, the analyses were initially conducted on a random selection of 70% of the total sample, and then validated on the remaining 30% of the sample. Analysis of covariance and multiple linear models were employed to estimate the associations between PNMS exposure, parent-child interactions in early life, and children's autistic-like behaviors. The results showed that PNMS exposure was positively associated with the presence of autistic-like behaviors at preschool age. The total indirect effect of the frequency of positive parent-child interactions in early life accounted for 9.69% or 8.99% of the variance of the association. Our findings indicate that parent-child interactions in early life might function as potential mediators of the association between PNMS and the increased risk of offspring autistic-like behaviors.

Comprehensive assessment of the ecological risk of exposure to triphenyl phosphate in a bioindicator tadpole.

The toxicity of triphenyl phosphate (TPhP) to aquatic organisms in surface waters has been demonstrated; However, an understanding of toxicity profiles of TPhP in amphibians is limited. Therefore, the adverse effects and threshold concentrations of TPhP on metamorphosis, growth, locomotion, and hepatic antioxidants of Gosner stage 25 Polypedates megacephalus tadpoles under long-term (35 d) exposure to six TPhP concentrations until complete metamorphosis were assessed. Additionally, the overall effect of using integrated multiple biomarkers were determined to demonstrate the potential ecological risks of waterborne TPhP at environmentally relevant concentrations in amphibian tadpoles. With increasing TPhP concentrations, physical parameters (snout-vent length, body mass, condition factor, and hepatic somatic index), jumping distance, hepatic catalase, and superoxide dismutase activities decreased, whereas metamorphosis time and malondialdehyde content increased. The threshold concentration of TPhP that affected the tadpole biomarker, except for metamorphosis rate and jumping distance, was 50-400 µg/L. Furthermore, the standardized scores of the examined integrated biomarkers in the six TPhP concentrations were visualized using radar plots and calculated as the integrated biomarker responses (IBRs). The varying TPhP concentrations had different scores in the radar plots, and the threshold for affecting the IBR value was 10 µg/L, which was close to the TPhP concentration in surface waters. Additionally, IBR values were strongly positively correlated with the TPhP concentrations. These findings indicate that environmentally relevant exposure to waterborne TPhP can pose an ecological risk to amphibian tadpoles. This study can serve as a reference and assist in the formulation of relevant policies and strategies to control TPhP pollution in water bodies.

Research progress on postoperative transient neurological dysfunction in pediatric and adult patients with moyamoya disease after revascularization surgery.

Moyamoya disease (MMD) is characterized by occlusion of the internal carotid artery (ICA) and its terminal branches, leading to compromised cerebral perfusion. Surgical revascularization is an effective therapy to improve cerebral hemodynamic. Transient neurological dysfunction (TND) usually occurs early after surgery and resolved within a few weeks without permanent neurologic deficit. In this article, we have reviewed the clinical features, mechanisms, and factors about TND in both pediatric and adult MMD patient.

Microbial Diversity of the Chinese Tiger Frog (Hoplobatrachus rugulosus) on Healthy versus Ulcerated Skin.

The Chinese tiger frog (Hoplobatrachus rugulosus) is extensively farmed in southern China. Due to cramped living conditions, skin diseases are prevalent among unhealthy tiger frogs which thereby affects their welfare. In this study, the differences in microbiota present on healthy versus ulcerated H. rugulosus skin were examined using 16S rRNA sequences. Proteobacteria were the dominant phylum on H. rugulosus skin, but their abundance was greater on the healthy skin than on the ulcerated skin. Rhodocyclaceae and Comamonadaceae were the most dominant families on the healthy skin, whereas Moraxellaceae was the most dominant family on the ulcerated skin. The abundance of these three families was different between the groups. Acidovorax was the most dominant genus on the healthy skin, whereas Acinetobacter was the most dominant genus on the ulcerated skin, and its abundance was greater on the ulcerated skin than on the healthy skin. Moreover, the genes related to the Kyoto Encyclopedia of Genes and Genomes pathways of levels 2-3, especially those genes that are involved in cell motility, flagellar assembly, and bacterial chemotaxis in the skin microbiota, were found to be greater on the healthy skin than on the ulcerated skin, indicating that the function of skin microbiota was affected by ulceration. Overall, the composition, abundance, and function of skin microbial communities differed between the healthy and ulcerated H. rugulosus skin. Our results may assist in developing measures to combat diseases in H. rugulosus.

Maternal exposure to cooking oil fumes during pregnancy and autistic-like behaviors in Chinese preschoolers.

There is growing evidence that cooking oil fumes (COFs) are harmful indoor air pollutants. However, there is a dearth of research investigating whether maternal COFs exposure during pregnancy may affect children's autistic-like behaviors in China. This study aimed to explore this association, and examine the effects of different cooking fuels and ventilation methods used by mothers on the presence of autistic-like behaviors. This study analyzed the survey data of the Longhua Child Cohort Study in 2017 with a total of 62,372 mothers enrolled in this study. A self-administrative questionnaire was used to collect information on socio-demographic characteristics, cooking habits during pregnancy, and autistic-like behaviors (measured using the Autism Behavior Checklist). After adjusting for potential confounders, the results showed that compared with children whose mothers never cooked during pregnancy, children whose mothers cooked sometimes, often, always during pregnancy had the higher risk of autistic-like behaviors. As the amounts of COFs exposed to and the frequency of cooking during pregnancy increased, the risk of a child's autistic-like behaviors also increased. Mothers using natural gas as cooking fuels had a lower risk of their child having autistic-like behaviors, compared with mothers using coal or other cooking fuels. Furthermore, pregnant women using ventilation measures during cooking significantly decreased likelihood of the presence of autistic-like behaviors in their children. These results suggest that maternal exposure to COFs during pregnancy may increase the likelihood of the presence of autistic-like behaviors in offspring. These findings support a recommendation that pregnant women should avoid exposure to COFs and use clean fuels and ventilation equipment in kitchens to reduce the risk of autistic-like behaviors in children.

Ecotoxicity assessment of triphenyl phosphate (TPhP) exposure in Hoplobatrachus rugulosus tadpoles.

Triphenyl phosphate (TPhP), a widely used aromatic organophosphate flame retardant, is known to accumulate in organisms through water, air, and soil, consequently, causing toxicity. This study is the first to evaluate the acute and sub-chronic toxicities of TPhP to amphibians. In the acute toxicity analysis, the 96-h median lethal concentration (LC50) for GS35 Hoplobatrachus rugulosus tadpoles was 2.893 mg/L, and the 10% effect concentration (EC10) was 289 µg/L. After two weeks of exposure to low TPhP concentrations, the survival and metamorphosis rates of H. rugulosus tadpoles decreased, and the metamorphosis time was prolonged as the TPhP concentration increased. The threshold concentration that affected tadpole survival and metamorphosis time was 50 µg/L and 100 µg/L, respectively. No significant differences were observed in the condition factor and hepatic somatic index of the tadpole after metamorphosis; however, tadpole body mass and TPhP concentration were negatively correlated. Further, TPhP inhibited the expressions of Cu-Zn sod and cat, thereby reducing the activities of superoxide dismutase and catalase in the tadpole liver. The threshold for affecting gene expression and enzymatic activity was 100 µg/L. These findings provide significant insights on the stress ecology of aquatic organisms.