Characterization of insulin-like growth factor 3 and its potential role in the spotted steed Hemibarbus maculatus ovary development.

As a new member of the insulin-like growth factors (Igfs), Igf3 was reported to play a vital role in fish reproduction. However, in spotted steed, the function of Igf3 remains largely unknown. In the present study, we identified and characterized Igf3 gene in spotted steed. Structural analysis showed that Igf3 contained five domains (B, C, A, D, E) and six conserved cysteine residues. The expression of Igf3 mRNA and protein were increased during ovary development and peaked in the maturation stage. The subcellular localization of IGF3 was highly expressed in granulosa cells and theca cells. Furthermore, recombinant IGF3 protein was produced and in vitro treatment with ovarian follicles significantly promoted the germinal vesicle breakdown (GVBD) rates of spotted steed follicles. The mRNA expression of cdc2 and cyclinB genes were significantly increased after IGF3 treatment, which were main components of maturation promoting factor (MPF). In addition, transcription levels of 3ß-hsd, 20ß-hsd, Cyp17a and Cyp19a1a were also changed. Taken together, these findings suggest that Igf3 is essential for ovary steroidogenesis and maturation in spotted steed.

N-Isopropylbenzylamine-induced conditioned place preference, sensitization behaviour and self-administration in rodents.

N-Isopropylbenzylamine (N-ipb), a chain isomer of methamphetamine (METH) with similar physical properties, has been used as a substitute for METH in seized drug samples. However, the abuse potential of N-ipb remains unclear. Therefore, this study aimed to evaluate the abuse potential of N-ipb in comparison to METH, by using conditioned place preference (CPP), locomotor sensitization and intravenous self-administration tests. The results showed that N-ipb at a dose of 3 mg·kg-1 significantly induced CPP in mice, which was comparable to the effect of METH at 1 mg·kg-1 . Either acute or repeated N-ipb injections (1 or 3 mg·kg-1 ) failed to raise the locomotor activity. However, acute treatment with 10 mg·kg-1 N-ipb elevated the locomotor activity compared with saline, while chronic injection of 10 mg·kg-1 N-ipb induced a delayed and attenuated sensitization compared with 1 mg·kg-1 METH. Rats could acquire N-ipb self-administration at a dose of 1 mg·kg-1 ·infusion-1 , and a typical inverted U-shaped dose-response curve was obtained for N-ipb. The mean dose of N-ipb that maintained the maximum response was greater than that of METH, indicating that N-ipb is less potent for reinforcement than METH. In the economic behavioural analysis, comparison of essential values derived from the demand elasticity revealed that N-ipb is less efficacy as a reinforcer than METH. The present data demonstrate that N-ipb functions as a reinforcer and has a potential for abuse. However, the potency of psychomotor stimulation and the reinforcing effectiveness of N-ipb are lower than those of METH.

Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats.

PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the reinstatement of heroin seeking induced by cues. Correlation analysis indicated that the inhibition of donepezil on heroin-seeking behaviour was positively correlated with an increased expression of dopamine receptor 1 (D1R) and dopamine receptor 2 (D2R) in the nucleus accumbens (NAc) and increased expression of choline acetyltransferase (ChAT) in the ventral tegmental area (VTA). CONCLUSIONS: The present study demonstrated that donepezil could inhibit heroin intake and heroin-seeking behaviour. Further, donepezil could regulate dopamine receptors in the NAc via an increase of acetylcholine. These results suggested that donepezil could be developed as a potential approach for the treatment of heroin misuse.

[A review of research on psychological and behavioral problems in children with autism spectrum disorder during the coronavirus disease 2019 epidemic]. / æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“æµè¡ŒæœŸé—´å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥å¿ƒç†è¡Œä¸ºé—®é¢˜çš„ç ”ç©¶æ¦‚å†µ.

Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.

Binary Au-Cu Reaction Sites Decorated ZnO for Selective Methane Oxidation to C1 Oxygenates with Nearly 100% Selectivity at Room Temperature.

Direct and efficient oxidation of methane to methanol and the related liquid oxygenates provides a promising pathway for sustainable chemical industry, while still remaining an ongoing challenge owing to the dilemma between methane activation and overoxidation. Here, ZnO with highly dispersed dual Au and Cu species as cocatalysts enables efficient and selective photocatalytic conversion of methane to methanol and one-carbon (C1) oxygenates using O2 as the oxidant operated at ambient temperature. The optimized AuCu-ZnO photocatalyst achieves up to 11225 µmol·g-1·h-1 of primary products (CH3OH and CH3OOH) and HCHO with a nearly 100% selectivity, resulting in a 14.1% apparent quantum yield at 365 nm, much higher than the previous best photocatalysts reported for methane conversion to oxygenates. In situ EPR and XPS disclose that Cu species serve as photoinduced electron mediators to promote O2 activation to •OOH, and simultaneously that Au is an efficient hole acceptor to enhance H2O oxidation to •OH, thus synergistically promoting charge separation and methane transformation. This work highlights the significances of co-modification with suitable dual cocatalysts on simultaneous regulation of activity and selectivity.

Tunicamycin-induced endoplasmic reticulum stress inhibits chemoresistance of FaDu hypopharyngeal carcinoma cells in 3D collagen I cultures and in vivo.

The prognosis in patients with advanced head and neck squamous cell carcinoma (HNSCC) is widely affected by the resistance to chemotherapy. As a culture scaffold, collagen I was showed to promote CSC (cancer stem cell) properties of cancer cells which could be used as in vitro models to study the chemoresistance in HNSCC. Endoplasmic reticulum (ER) stress is a cellular stress condition which could affect tumor progression and promote the anti-tumor effects of certain drugs. However, the impact of ER stress on collagen I induced CSC properties and chemoresistance of HNSCC cells has not been addressed. In this study we investigated the effects of tunicamycin (TM) induced ER stress on the stemness and sensitivity to chemotherapeutic drugs of FaDu hypopharyngeal carcinoma cells in 3D (three-dimensional) collagen I cultures and mouse xenograft models. Our study revealed that Collagen I scaffold promoted CSC properties and increased G1 population of FaDu cells in 3D cultures, accompanied by maturation of integrin ß1 and enhanced activated TGF-ß1 concentration. Compared to 2D (two-dimensional) cultured cells, cells in 3D Collagen I scaffold exhibited significantly increased resistance to chemotherapeutic drugs of cisplatin and paclitaxel. Further analysis revealed that TM induced ER stress preferentially attenuated chemoresistance of FaDu cells in 3D collagen I, downregulated their CSC properties and TGF-ß1 concentration and resulted in deglycosylation of integrin ß1. TM was further evaluated in the mouse xenograft models and showed significant tumor growth inhibition in combination with paclitaxel than either TM or paclitaxel alone. Taken together, Our findings suggest that TM-induced ER stress potentiates anticancer efficacy of FaDu cells in 3D cultures and in vivo, and highlight implications for targeting chemotherapy-resistant cancer stem cells under ER stress conditions.

Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.

OBJECTIVE: Genetic variations can affect individual response to methadone maintenance treatment (MMT) for heroin addiction. The A118G variant (rs1799971) in the mu opioid receptor gene (OPRM1) is a potential candidate single nucleotide polymorphism (SNP) for personalized MMT. This study determined whether rs1799971 is related to MMT response or dose. METHODS: We recruited 286 MMT patients from a Han Chinese population. The rs1799971 genotype was determined via TaqMan genotyping assay. The genetic effect of this SNP on MMT response or dose was evaluated using logistic regression. A meta-analysis was performed to merge all available data to evaluate the role of rs1799971 in MMT using RevMan 5.3 software. RESULTS: No statistical significance was observed in the association between the OPRM1 rs1799971 and MMT response or dose in our Chinese cohort. Meta-analysis indicated that the OPRM1 A118G variation was not significantly associated with MMT response or dose requirement. CONCLUSION: The results suggest that rs1799971 in OPRM1 might not play a critical role alone in influencing MMT response or dose.

Identification of ribosomal protein L24 (RPL24) from the oriental river prawn, Macrobrachium nipponense, and its roles in ovarian development.

Ribosomal proteins exhibit various extraribosomal functions in addition to their roles in protein synthesis. In this study, complementary DNA (cDNA) of ribosomal protein L24 in Macrobrachium nipponense (MnRPL24) was isolated, and its role in ovarian development was investigated using quantitative real-time PCR (qPCR), immunohistochemistry (IHC), RNA interference (RNAi) and histological observations. The complete cDNA of MnRPL24 is 564 base pairs (bps) and contains a 486 bp open reading frame (ORF) encoding 162 amino acids (aas). The highest expression level of MnRPL24 among eight tissues was found in the ovary, specifically in the stage I ovary. The MnRPL24 protein existed in the cytoplasm and nucleus of developing oocytes, and also existed in the cytoplasm of follicle cells in developing ovaries. After MnRPL24 knockdown by RNAi, the expression levels of vitellogenin (Vg), vitellogenin receptor (Vgr), cyclin-dependent kinase 2 (Cdc2) and M-phase cyclin (Cyclin B) genes and the gonadsomatic index (GSI) did not show the typical trend of gradually elevation with ovarian development and finally decrease in the later stage of ovarian cycle. Moreover, the oviposition rate (OR) was downregulated, and oocyte development was delayed after MnRPL24 knockdown. After eyestalk ablation, the MnRPL24 expression level was considerably elevated in the initial stages and decreased in the late stage of the ovarian development cycle. This investigation illustrates a possible regulatory role of MnRPL24 in the ovarian development of M. nipponense, and MnRPL24 may act as a stimulator of early ovarian development.

Transcriptome analysis of common carp (Cyprinus carpio) provides insights into the ovarian maturation related genes and pathways in response to LHRH-A and dopamine inhibitors induction.

Luteinizing hormone-releasing hormone analog (LHRH-A) and dopamine inhibitors have been widely used to induce oocyte maturation and ovulation in domesticated fishes. Although this approach represents a reliable method for regulating fish reproduction, the underlying molecular mechanisms mediating LH action are largely unexplored. The objective of this study was to determine the transcriptional profile of gene programming in hormone-treated common carp. In the present study, female common carp were intraperitoneally injected with LHRH-A together with dopamine inhibitors, and control fish were injected with saline. Ovarian morphological changes were analysed by both light microscopy and scanning electron microscopy. Furthermore, gene expression profiling of the brain and ovarian tissues was performed by Illumina sequencing. Compared to the control carp, hormone treatment resulted in morphological changes including disappearance of nuclear membrane, breakdown of germinal vesicle (GVBD), and fusion of yolk globules, reflecting that hormones significantly promoted oocyte maturation. In comparison to control, we have identified 867 and 9,053 differentially expressed genes in the hormone-treated female brain and ovary, respectively. In the brain, most of the identified genes were significantly enriched in 18 KEGG pathways. In the ovarian tissue, the identified genes were significantly involved in 9 pathways. In the hormone-treated carp, genes were involved in calcium signalling pathway, cAMP signalling pathway, insulin secretion, and oxidative phosphorylation pathway, which showed obvious associations with ovarian maturation. The present study provides transcriptomic information for hormone-treated carp, which might be useful for studying the endocrine regulation and mechanisms of ovarian maturation in domesticated fishes.

Akt and its phosphorylation in nucleus accumbens mediate heroin-seeking behavior induced by cues in rats.

Akt is initially identified as one of the downstream targets of phosphatidylinositol-3 kinase (PI3K) and is involved in morphine reward and tolerance. However, whether phospholyration of Akt (p-Akt) mediates heroin relapse remains unclear. Here, we aimed to explore the role of p-Akt in the nucleus accumbens (NAc) in cue-induced heroin-seeking behaviors after withdrawal. First, rats were trained to self-administer heroin for 14 days, after which we assessed heroin-seeking behaviors induced by a context cue (CC) or by discrete conditioned cues (CS) after 1 day or 14 days of withdrawal. We found that the active responses induced by CC or CS after 14 days of withdrawal were higher than those after 1 day of withdrawal. Meanwhile, the expression of p-Akt in the NAc was also greatest when rats were exposed to the CS after 14 days of withdrawal. Additionally, a microinjection of LY294002, an inhibitor of PI3K, into the NAc inhibited the CS-induced heroin-seeking behaviors after 14 days of withdrawal, paralleling the decreased levels of p-Akt in the NAc. Finally, Akt1 or ß-arrestin 2 was downregulated via a lentiviral injection to assess the effect on heroin seeking after 14 days of withdrawal. CS-induced heroin-seeking behavior was inhibited by downregulation of Akt1, but not ß-arrestin 2, in the NAc. These data demonstrate that Akt phosphorylation in the NAc may play an important role in the incubation of heroin-seeking behavior, suggesting that the PI3K/Akt pathways may be involved in the process of heroin relapse and addiction.

All-trans retinoic acid reduces cancer stem cell-like cell-mediated resistance to gefitinib in NSCLC adenocarcinoma cells.

BACKGROUND: The enrichment of cancer stem cell-like cells (CSCs) has been considered to be responsible for tumor progression after an initial response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung adenocarcinoma (NSCLC/ADC). CSCs with ALDH1A1bright /CD44high expression contribute to the TKIs resistance in NSCLC/ADC cells. All-trans retinoic acid (ATRA) has been shown to be a potential targeted therapy against CSCs due to its ability to inhibit ALDH1A1 activity. We therefore investigated whether ATRA could circumvent the resistance to improve the response to gefitinib in NSCLC/ADC cells. METHODS: Treatment of NSCLC/ADC A549 and H1650 cells with gefitinib enriched the gefitinib surviving cells (GSCs). The expression of ALDH1A1 and CD44 and the IC50 values for gefitinib were determined by flow cytometry (FCM) and crystal violet assay in GSCs and ATRA-treated GSCs, respectively. Using DEAB as the positive control, direct inhibitory effect of ATRA on ALDH1A1 activity was determined by ALDEFLUOR assay, RESULTS: GSCs showed higher expression of ALDH1A1 and CD44 and IC50 values for gefitinib than their respective parental cells, suggesting that gefitinib can lead to propagation of CSC-enriched gefitinib-resistant cells. Treatment with ATRA was found to significantly reduce the increased expression of ALDH1A1 and CD44 and the IC50 values for gefitinib in A549GSC and H1650GSC cells, and ATRA could directly inhibit active ALDH1A1 as compared to DEAB. CONCLUSION: Our findings suggest that combination treatment with ATRA prevents gefitinib-induced enrichment of ALDH1A1bright/CD44high CSCs and enhances gefitinib-induced growth inhibition of NSCLC/ADC cells.

Increased expression of plasma hsa-miR-181a in male patients with heroin addiction use disorder.

BACKGROUND: Drug addiction is an uncontrolled, chronic, and recurrent encephalopathy that presently lacks specific and characteristic biomarkers for diagnosis and treatment. As regulators of gene expression, microRNAs (miRNAs) are increasingly used for diagnostic and prognostic purposes in various disease states. Previous studies indicated that miRNAs play important roles in the development and progression of drug addictions, including addiction to methamphetamine, cocaine, alcohol, and heroin. METHODS: We identified significant miRNAs using the microarray method and then validated the hsa-miR-181a expression levels in 53 heroin addiction patients and 49 normal controls using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the potential associations between transcriptional levels in heroin addiction patients and their clinicopathological features were analyzed. RESULTS: A total of 2006 miRNAs were differentially expressed between heroin addiction patients and normal controls. The top 10 up-regulated miRNAs in patients were hsa-miR-21a, hsa-miR-181a, hsa-miR-4459, hsa-miR-4430, hsa-miR-4306, hsa-miR-22-3P, hsa-miR-486-5P, hsa-miR-371b-5P, hsa-miR-92a-3P, and hsa-miR-5001-5P. The top 10 down-regulated miRNAs in patients were hsa-miR-3195, hsa-miR-4767, hsa-miR-3135b, hsa-miR-6087, hsa-miR-1181, hsa-miR-4785, hsa-miR-718, hsa-miR-3141, hsa-miR-652-5P, and hsa-miR-6126. The expression level of hsa-miR-181a in heroin addiction patients was significantly increased compared with that in normal controls (P < .001). The area under the receiver operating characteristic curve of hsa-miR-181a was 0.783, the sensitivity was 0.867, and the specificity was 0.551. CONCLUSIONS: The increased expression of hsa-miR-181a in the plasma of heroin patients may be a consequence of the pathological process of heroin abuse. This study highlights the potential of hsa-miR-181a as a novel biomarker for the diagnosis of heroin addiction.

Cloning and characterization of wnt4a gene in a natural triploid teleost, Qi river crucian carp (Carassius auratus).

WNT4 (wingless-type MMTV integration site family, member 4) plays a key role in the ovarian differentiation and development in mammals. However, the possible roles of Wnt4 during gonadal differentiation and development need further clarification in teleosts. In this study, we cloned and characterized the full-length cDNA of Qi river crucian carp (Carassius auratus) wnt4a gene (CA-wnt4a). The cDNA of CA-wnt4a is 2337 bp, including the ORF of 1059 bp, encoding a putative protein with a transmembrane domain and a WNT family domain. Sequence and phylogenetic analyses revealed that the CA-Wnt4a identified is a genuine Wnt4a. Tissue distribution analysis showed that CA-wnt4a is expressed in all the tissues examined, including ovary. CA-wnt4a undergoes a stepwise increase in the embryonic stages, suggesting that CA-wnt4a might be involved in the early developmental stage. Ontogenic analysis demonstrated that CA-wnt4a expression is upregulated in the ovaries at 30-50 days after hatching (dah), the critical period of sex determination/differentiation in Qi river crucian carp. From 90 dah, the expression of CA-wnt4a was gradually downregulated in the developing ovaries. Immunohistochemistry demonstrated that CA-Wnt4a was expressed in the somatic and germ cells of the ovary by 30 dah, thereafter, positive signals of Wnt4a were detected in the somatic cells, oogonia and primary growth oocytes from 60 dah. In the sex-reversed testis induced by letrozole treatment, the expression level of CA-wnt4a was significantly downregulated. When CA-wnt4a expression was inhibited by injection of FH535 (an inhibitor of canonical Wnt/ß-catenin signal pathway) in the ovaries, levels of cyp19a1a, foxl2 mRNA were significantly downregulated, while sox9b and cyp11c1 were upregulated, which suggested that together with Foxl2-leading estrogen pathway, CA-wnt4a signaling pathway might be involved in ovarian differentiation and repression of the male pathway gene expression in Qi river crucian carp.

Dorsolateral striatal miR-134 modulates excessive methamphetamine intake in self-administering rats.

Increasing evidence indicates that excessive drug consumption is sufficient for the transition from recreational and controlled drug use to uncontrolled use and addiction. However, the underlying mechanisms are debated. Some neurobehavioral and neuroimaging evidence indicates that dorsolateral striatum (dlStr)-dependent habit learning plays a key role in excessive drug intake and the transition to addiction, but little is known about the molecular events. The present study investigated whether dlStr miR-134, an important regulator of synaptic transmission and plasticity, is involved in excessive methamphetamine intake. We established excessive and uncontrolled methamphetamine self-administration model in rats by permitting animals extended access to drug (6 h/session/d, LgA group), whereas animals that were limited to access to drug (2 h/session/d, ShA group) exhibited low and controlled self-administration. miR-134 expression in dlStr was significantly increased and its target LIMK1 expression was decreased in the LgA group, but not in the ShA group, compared with the saline control group. However, passive methamphetamine exposure did not alter miR-134 and LIMK1 levels in dlStr. We also found that down-regulation of miR-134 in dlStr through local microinjection of a lentivirus carrying miR-134 sponge (LV-miR-134-Sil) significantly reduced methamphetamine infusions and excessive consumption in LgA group, rather than ShA group. These results indicated that dlStr miR-134, perhaps via its target LIMK1, contributed to excessive and uncontrolled methamphetamine intake, supporting the hypothesis that stimulus-response habit formation is an important mechanism underlying the transition from controlled drug use to uncontrolled drug use and addiction.

Digital planning workflow for partial maxillectomy using an osteotomy template and immediate rehabilitation of maxillary Brown II defects with prosthesis.

BACKGROUND: There is increasing evidence of benefits for the rehabilitation of Brown II defects with prosthesis in surgery. However, the current literature is sparse for maxillary tumour resection using osteotomy templates. OBJECTIVES: To assess the accuracy of maxillectomy using a custom fabricated osteotomy template and to evaluate the prosthesis for surgical accuracy, appearance and functioning (speech, swallowing and occlusal force). METHODS: Ten patients with Brown II defects caused by tumour resection were treated with precise partial maxillectomy using an osteotomy template. The immediate rehabilitation of the Brown II defect was completed with a prefabricated prosthesis. The post-operative three-dimensional images and the pre-operative virtual images were superimposed, and average deviation and maximum deviation were calculated. Speech intelligibility, swallowing, appearance and University of Washington Quality of Life Questionnaire (UW-QoL) were examined at 1, 3 and 6 months after surgery. Occlusal force was examined post-operatively at 6 months. RESULTS: The maximum deviation between the actual and virtual surgery was 5.12 ± 0.44 mm, with an average of 1.02 ± 0.17 mm. Speech intelligibility, swallowing and UW-QoL improved significantly (P < .05) after wearing the prosthesis. The recovery index of the occlusal force on the affected side was 20.19%-32.28%. The skewed degree of the mouth corner, the difference in the height of the left and right lips, the maximum deviation distance and the change area volume decreased significantly (P < .05). CONCLUSION: The precise rehabilitation of maxillary Brown II defects can be achieved using a prosthesis fabricated with an osteotomy template. The prosthesis restored appearance and functional capabilities (such as speech and occlusal force).

[Relationship Between LEP G2548A Polymorphism and Cholesterol Gallstone].

OBJECTIVES: To determine the associations of single nucleotide polymorphism (SNP) in leptin (LEP) genes and environmental factors with cholesterol gallstone in southeast Han populations. METHODS: A 1:2 matched case-control study was conducted involving 200 patients with cholesterol gallstone. Genotyping of the SNP was examined on the LightCycler480 PCR platform using in-house high resolution melting (HRM) approaches. Detection correctness was validated through direct sequencing. Multifactor dimensionality reduction (MDR) analysis was applied to examine the effects of potential gene-environment interactions. RESULTS: Three genotypes of LEP G2548A were obtained by HRM genotyping, including 52 cases of GG wild type, 192 cases of GA mutant heterozygosity and 356 cases of AA mutation homozygous type. The genotype distribution of the SNP locus in the control group was in line with the Hardy-Weinberg genetic balance (P>0.05). The AA genotype carriers of LEP G2548A had significantly higher serum leptin than the GA/GG genotype carriers (H=6.83, P<0.05). The conditional logistic regression revealed that high serum leptin [odds ratio (OR)=5.012, 95% confidence interval (CI): 3.248-7.734], AA genotype of LEP G2548A site (OR=2.292, 95%CI: 1.012-5.193), family history of gallstones (OR=2.984, 95%CI: 1.329-6.700), high SBP (OR=1.927, 95%CI: 1.140-3.255) and smoking (OR=1.717, 95%CI: 1.006-2.928) were predictors of cholesterol gallstone. However, regular drinking of strong tea (OR=0.552, 95%CI: 0.336-0.907) and exercise (OR=0.591, 95%CI: 0.395-0.882) were protecting factors for cholesterol gallstone. The results of MDR analysis indicated that tea drinking, genotype of LEP G2548A site and serum leptin formed the optimal gene-environment interaction model. CONCLUSIONS: Individuals who drink less tea, carry AA genotype and have high serum leptin are more susceptible to cholesterol gallstone.

A heroin addiction severity-associated intronic single nucleotide polymorphism modulates alternative pre-mRNA splicing of the µ opioid receptor gene OPRM1 via hnRNPH interactions.

Single nucleotide polymorphisms (SNPs) in the OPRM1 gene have been associated with vulnerability to opioid dependence. The current study identifies an association of an intronic SNP (rs9479757) with the severity of heroin addiction among Han-Chinese male heroin addicts. Individual SNP analysis and haplotype-based analysis with additional SNPs in the OPRM1 locus showed that mild heroin addiction was associated with the AG genotype, whereas severe heroin addiction was associated with the GG genotype. In vitro studies such as electrophoretic mobility shift assay, minigene, siRNA, and antisense morpholino oligonucleotide studies have identified heterogeneous nuclear ribonucleoprotein H (hnRNPH) as the major binding partner for the G-containing SNP site. The G-to-A transition weakens hnRNPH binding and facilitates exon 2 skipping, leading to altered expressions of OPRM1 splice-variant mRNAs and hMOR-1 proteins. Similar changes in splicing and hMOR-1 proteins were observed in human postmortem prefrontal cortex with the AG genotype of this SNP when compared with the GG genotype. Interestingly, the altered splicing led to an increase in hMOR-1 protein levels despite decreased hMOR-1 mRNA levels, which is likely contributed by a concurrent increase in single transmembrane domain variants that have a chaperone-like function on MOR-1 protein stability. Our studies delineate the role of this SNP as a modifier of OPRM1 alternative splicing via hnRNPH interactions, and suggest a functional link between an SNP-containing splicing modifier and the severity of heroin addiction.

[Levels of phthalate internal exposure levels in pregnant women and influencing factors].

OBJECTIVE: To investigate the levels and influencing factors of phthalate internal exposure in pregnant women (gestation age ≤ 16 weeks). METHODS: During April to June in 2013, 1 020 pregnant women (gestation age ≤ 16 weeks) who had established the maternal care manual were recruited in maternal and child health hospital of Siming District, Xiamen city. Participators were asked to complete a questionnaire to obtain information on socio-demographic characteristics, lifestyle behaviors, and antenatal examination and to provide a urine sample. Finally, 998 pregnant women who provided a urine sample and completed the questionnaire were enrolled. Adopting systematic sampling method, 100 ones were selected randomly among 998 pregnant women. High performance liquid chromatography-electrospray ionization-tandern mass was used to determine the concentration of five phthalate monoesters in each urine, including mono-n-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), mono-ethylhexyl phthalate (MEHP). Based on the measurements and questionnaire data, multivariate logistic regression was used to analyze the association between the phthalate monoester levels and potential influential factors. RESULTS: The detection rates of MMP, MEP, MBP, MBzP and MEHP in 100 pregnant urine samples were 94%, 93%, 87%, 83%, 99%, respectively. And the urinary median uncorrected concentrations of MMP, MEP, MBP, MBzP and MEHP in 100 urine samples were 20.56, 17.62, 10.15, 2.03, and 5.12 ng/ml, respectively. Specific gravity-corrected concentration were 20.81, 20.36, 12.88, 2.58, 5.00 ng/ml, respectively. The results of multivariate logistic regression analysis indicated that: education degree was negatively associated with urinary concentration of MMP, MEP, MBP, MBzP and MEHP, OR (95% CI) were 0.495 (0.253-0.966), 0.380 (0.191-0.755), 0.379 (0.186-0.774), 0.401 (0.196-0.819), 0.373(0.183-0.762), respectively. Participants who had hair permed and dyed during pregnancy had higher urinary level of MBP and MBzP, OR (95% CI) were 12.867 (1.240-133.525), 15.982 (1.367-186.911), respectively; Participants who use cosmetics during pregnancy had higher urinary level of MEP and MBP, OR (95% CI) were 2.977 (1.012-8.757), 4.440 (1.485-13.272), respectively; plastic bottled water consumption was positively associated with urinary concentrations of MEP and MEHP, OR (95% CI) were 3.780 (1.417-10.083), 2.699 (1.039-7.010), respectively; annual household income was negatively associated with urinary concentration of MMP, OR (95% CI) was 0.597 (0.372-0.959); individuals who took medications during pregnancy had higher urinary level of MEHP than non-takers, OR (95% CI) was 4.853 (1.084-21.732). CONCLUSION: Pregnant women whose gestation age was less than 16 weeks are generally exposed to phthalate. Phthalate internal exposure levels are significantly associated with most measured factors and the influencing factors with different phthalates internal exposure levels are different.

Adsorption of hexavalent chromium onto organic bentonite modified by the use of iron(III) chloride.

The adsorption of hexavalent chromium (Cr(VI)) was improved by using organic bentonite (OB) modified with iron(III) chloride. The adsorption mechanisms and characteristics of OB and organic bentonite modified by FeCl3 (FMOB) were studied by using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy (EDS). It was found that hydroxyl-iron replaced some of the calcium and magnesium contained in the FMOB, but no significant change in its structure was shown even though the adsorption experiments proved that FMOB had a better Cr(VI) adsorption ability compared to OB. The coated material was prepared by mixing FMOB and 4A molecular sieves in a coated pot for the adsorption experiments in the test column. The relevant results showed that the adsorption of the coated material retained its high adsorption ability and maintained that ability after desorption and regeneration, which implied a potential for further application.

Comparison of the efficacy and tolerability of different repetitive transcranial magnetic stimulation modalities for post-stroke dysphagia: a systematic review and Bayesian network meta-analysis protocol.

INTRODUCTION: Up to 78% of patients who had a stroke develop post-stroke dysphagia (PSD), a significant consequence. Life-threatening aspiration pneumonia, starvation, and water and electrolyte abnormalities can result. Several meta-analyses have shown that repeated transcranial magnetic stimulation (rTMS) improves swallowing in patients who had a stroke; however, the optimum model is unknown. This study will be the first Bayesian network meta-analysis (NMA) to determine the best rTMS modalities for swallowing of patients who had a stroke. METHODS AND ANALYSIS: PubMed, Web of Science, Embase, Google Scholar, Cochrane, the Chinese National Knowledge Infrastructure, the Chongqing VIP Database and WanFang Data will be searched from their creation to 2 September 2023. All randomised controlled trials associated with rTMS for PSD will be included. Only Chinese or English results will be studied. Two researchers will independently review the literature and extract data, then use the Cochrane Collaboration's Risk of Bias 2.0 tool to assess the included studies' methodological quality. The primary outcome is swallowing function improvement, whereas secondary outcomes include side effects (eg, paraesthesia, vertigo, seizures) and quality of life. A pairwise meta-analysis and NMA based on a Bayesian framework will be conducted using Stata and R statistical software. The Grading of Recommendations Assessment, Development, and Evaluation system will assess outcome indicator evidence quality. ETHICS AND DISSEMINATION: As all data in this study will be taken from the literature, ethical approval is not needed. We will publish our work in peer-reviewed publications and present it at academic conferences. PROSPERO REGISTRATION NUMBER: CRD42023456386.