Association of the KISS1, LIN28B, VDR and ERα gene polymorphisms with early and fast puberty in Chinese girls.

OBJECTIVES: To explore the association of KISS1, LIN28B, vitamin D receptor (VDR), and estrogen receptor α (ERα) gene polymorphisms and the risk of early with fast puberty (EFP) risk, and with hormone levels in EFP cases, in Chinese girls. METHODS: The analysis was based on the data of 141 girls with EFP and 152 girls without EFP. Clinical features were documented, and all SNP genotyping was conducted using SNaPshot method. Statistical analysis was performed to assess the association of the SNPs with EFP risk, and with hormone levels in EFP cases. RESULTS: There was a significant association between rs7759938-C polymorphism in the LIN28B gene and the risk for EFP in the recessive (TT + CT vs. CC) model (p = 0.040). Remarkably, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene were significantly associated with peak LH (luteinizing hormone) levels (p = 0.008, 0.045) and peak LH/FSH (follicle-stimulating hormone) ratio (p = 0.007, 0.006). Additionally, on 7 of the 8 variant loci the alleles associated with increased levels of both peak LH levels and peak LH/FSH ratio in EFP cases were also associated with increased CPP risk. CONCLUSIONS: Our findings indicate that rs7759938-C polymorphism in the LIN28B gene might have a protective effect on EFP susceptibility. The most striking findings of this study is that, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene influenced levels of GnRH-stimulated peak LH and LH/FSH ratio, and in general CPP risk genes might also contributes to the abnormality of hormonal levels in EFP.

Konjaku flour reduces obesity in mice by modulating the composition of the gut microbiota.

BACKGROUND: Changes in the intestinal flora composition is referred to as dysbiosis, which is related to obesity development, thus supporting the potential roles of nutrients acting on intestinal flora to exert salutary effects on energetic metabolism of host. Dietary fiber has been known to affect the composition of intestinal flora. The aim of the present study was to investigate the functional effects of konjac flour (KF) on obesity control in respect to improving inflammation, metabolism, and intestinal barrier function, and the possible association of the effects with intestinal flora composition changes. METHODS: Mice (n = 30) were randomly divided into control group (n = 10), high-fat-diet (HFD) group (n = 10), and KF intervention group (n = 10), followed by feeding for 12 weeks and with adding a KF daily supplementation for the treatment group. Body weight, fat accumulation, inflammation, and energetic metabolism markers in multiple tissues and the gut microbiota of the mice were examined at the end of the experiment. RESULTS: The KF supplementation significantly reduced the gains in weight, fat mass, as well as adipocyte size of HFD mice and lowered the serum TC, leptin (LEP), thiobarbituric acid-reacting substance (TBARS), IL-6, and lipopolysaccharide (LPS) levels in HFD mice. KF also upregulated the expression of intestinal mucosa protein gene Intection and tight junction ZO-1 in HFD mice, as well as upregulate the expression of energy metabolism genes PPARα and CPT-1 as well as the fat metabolism gene HLS in livers and fat tissues, and downregulate that of fat synthesis gene PPARγ (p < 0.05). The KF treatment increases the α-diversity and change the ß-diversity of the intestinal microflora in HFD mice and boosted the abundances of some obesity-related beneficial microorganisms (such as Megasphaera elsdenii) in the intestinal microflora of HFD mice, while reduced those of harmful microorganisms (such as Alistipes, Alloprevotella, Bacteroides acidifaciens, and Parabacteroides goldsteinii). The abundance of Alistipes was positively correlated with weight, fat mass, serum TC, TG, LEP, IL-6, and LPS contents as well as PPARγ gene expression; while notably and negatively related to the expression of CPT-1 and HLS genes (p < 0.01). KF remarkably increased the abundance of Aerococcaceae, while reduced that of Alistipes finegoldii (p < 0.01). CONCLUSIONS: Supplementation with KF achieves favorable effects on treating obesity, improving inflammatory response, metabolism, and intestinal barrier function, by regulating intestinal microfloral structure in HFD-fed mice.

Black silicon Schottky photodetector in sub-bandgap near-infrared regime.

Sub-bandgap near-infrared silicon (Si) photodetectors are key elements in integrated Si photonics. We demonstrate such a Si photodetector based on a black Si (b-Si)/Ag nanoparticles (Ag-NPs) Schottky junction. This photodetector synergistically employs the mechanisms of inner photoemission, light-trapping, and surface-plasmon-enhanced absorption to efficiently absorb the sub-bandgap light and generate a photocurrent. The b-Si/Ag-NPs sample was prepared by means of wet chemical etching. Compared to those of a planar-Si/Ag thin-film Schottky photodetector, the responsivities of the b-Si/Ag-NPs photodetector were greatly enhanced, being 0.277 and 0.226 mA/W at a reversely biased voltage of 3 V for 1319- and 1550-nm light, respectively.

Advanced Parental Age Impaired Fear Conditioning and Hippocampal LTD in Adult Female Rat Offspring.

Advanced maternal or paternal age is associated with increased risks of cognitive and emotional disorders. Chronic stress is also a common experience in human life that causes psychiatric diseases. However, the synergistic effects of these two factors on offspring are rarely studied. In the present study, the offspring of both young (3-4 months) and old (12-14 months) rat parents were given CUMS for 21 days at the age of 4 weeks. The effects of advanced parental age and chronic unpredictable mild stress (CUMS) on emotional and cognitive behaviors and the related cellular mechanisms were investigated by using behavioral and electrophysiological techniques. We found that CUMS decreased sucrose consumption, increased anxiety, and impaired learning and memory in offspring from both old and young breeders. However, advanced parental age impaired fear memory and spatial memory mainly in female offspring. The serum corticosterone of female offspring was lower than males, but advanced parental age significantly elevated serum corticosterone in female offspring in response to electrical foot shocks. In addition, hippocampal LTD was severely impaired in female offspring from older parents. Our results indicated that female offspring from older breeders might be more sensitive to stress, and the hippocampal function was more vulnerable. These results might provide experimental basis for the prevention and treatment of advanced parental age related psychiatric disorders in future.

[Progress in the molecular genetic mechanism of gonadoblastoma].

Gonadoblastoma (GB), a rare in situ germ cell tumor derived from sex cord and germ cells, is closely associated with gonadal dysgenesis. About 80% of GB individuals exhibit 46, XY female phenotype while the others are 45, XY and 46, XX with disorders of sex development. Moreover, 35% of GB can eventually develop into malignant tumors, such as seminoma and dysgerminoma tumors. The molecular genetic mechanism of GB remains to be fully uncovered due to phenotypic and genetic heterogeneity. Increasing studies show that the formation of GB is closely related to genes regulating sexual differentiation and determination (e.g., SRY, WT1, SOX9, Foxl2, TSPY, etc), and is affected by the interaction of genetic and epigenetic regulation. Here we describe the clinical and pathological features, diagnosis and treatment of GB, and also summarize the molecular genetic and epigenetic mechanisms underlying the gonadal abnormalities that lead to GB. We analyze and construct the common gene regulatory networks related to the development of GB, and describe some obstacles and deficiencies in current studies to provide innovative perspectives on further studying the pathological and molecular mechanisms of GB.

A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.

The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior.

Overexpression of NOP58 Facilitates Proliferation, Migration, Invasion, and Stemness of Non-small Cell Lung Cancer by Stabilizing hsa_circ_0001550.

BACKGROUND: NOP58 ribonucleoprotein (NOP58) is associated with the recurrence of lung adenocarcinoma. AIMS: Few investigations concentrate on the role of NOP58 in non-small cell lung cancer (NSCLC), which is the focus of our current study. METHODS: Following transfection, the proliferation, migration, and invasion of NSCLC cells were assessed by 5- ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays. The percentage of CD9+ cells was evaluated by flow cytometry assay. Based on target genes and binding sites predicted through bioinformatics analysis, a dual-luciferase reporter assay was performed to verify the targeting relationship between hsa_circ_0001550 and NOP58. The effect of NOP58 overexpression on hsa_circ_0001550 stability was gauged using Actinomycin D. The hsa_circ_0001550 and NOP58 expression levels, as well as protein expressions of CD44, CD133, OCT4, and SOX2 in NSCLC cells were determined by quantitative real-time PCR and Western blot, respectively. RESULTS: Hsa_circ_0001550 was remarkably up-regulated in NSCLC cell lines A549 and PC9, silencing of which weakened cell abilities to proliferate, migrate and invade, decreased CD9+ cell ratio, and diminished protein expressions of CD44, CD133, OCT4, and SOX2. NOP58 could bind to hsa_circ_0001550 and stabilize its expression, and NOP58 overexpression partially abrogated hsa_circ_0001550 knockdown-inhibited NSCLC cell proliferation, migration, invasion and stemness. CONCLUSION: Overexpression of NOP58 facilitates proliferation, migration, invasion, and stemness of NSCLC cells by stabilizing hsa_circ_0001550, hinting that NOP58 is a novel molecular target for NSCLC therapy.

The association between serum albumin and alkaline phosphatase in cancer patients.

The role of serum albumin (ALB) has been extensively studied in patients with cancer; however, research on its effect on bone metastasis in these patients remains limited. This study aimed to investigate the relationship between serum ALB and alkaline phosphatase (ALP) levels in patients with tumors. Using data from the National Health and Nutrition Examination Survey 2011 to 2018, we assessed the correlation between serum ALB and ALP levels using a weighted multivariate linear regression model, whereas a weighted generalized additive model and smooth curve fitting were used to address potential nonlinearities. A total of 1876 patients with cancer were included in our study. In the subgroup analysis stratified by sex, race/ethnicity, and liver disease, the negative correlation of ALB with ALP remained for most groups, except in blacks (ß = -1.755, 95%CI: [-3.848, 0.338], P = .103) and patients with gout (ß = -0.676, 95%CI: [-2.061, 0.709], P = .340). In black people and patients with gout, the relationship between ALB and ALP showed an inverted U-shaped curve, with an inflection point at approximately 42 g/dL. Our study showed an inverse correlation between ALB and ALP levels in most patients with tumors, but not in black patients and those with gout. The measurement of ALB levels can serve as a screening tool for bone metastases while guiding therapeutic intervention strategies.

A rare malignant mesothelioma of the tunica vaginalis testis: A case report.

Malignant mesothelioma of the tunica vaginalis testis is a rare, highly invasive urogenital malignant tumor with no specific clinical manifestations. Reported cases of this disease are limited. Therefore, an early preoperative diagnosis is difficult. The current study presents a case of malignant mesothelioma of the tunica vaginalis testis and a literature review. A 52-year-old man was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) in December 2022 and underwent radical resection of the right testicle and epididymis but did not undergo radiotherapy or chemotherapy. The patient was followed up for 5 months, and no recurrence or metastasis was found. The rarity of testicular mesothelioma poses a challenge to its etiology and diagnosis, which is rarely achieved preoperatively. Malignant mesothelioma of the testicular tunica vaginalis has a poor prognosis and is not sensitive to radiotherapy or chemotherapy, requiring close postoperative follow-up. This condition is rare in clinical practice; therefore, it needs to be reported to aid clinicians' decision-making regarding diagnosis and treatment.

Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility.

Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30% of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r (2) = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42%) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking.

Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease.

RATIONALE: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. OBJECTIVES: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. METHODS: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-α) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P < 1 × 10(-8)), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. MEASUREMENTS AND MAIN RESULTS: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P = 0.009-0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P = 0.001-0.049), although these COPD associations were not replicated in two additional cohorts. CONCLUSIONS: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).

Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35) and <10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.

Accumulated Lattice Strain as an Intrinsic Trigger for the First-Cycle Voltage Decay in Li-Rich 3d Layered Oxides.

Li- and Mn-rich layered oxides (LMLOs) are promising cathode materials for Li-ion batteries (LIBs) owing to their high discharge capacity of above 250 mA h g-1. A high voltage plateau related to the oxidation of lattice oxygen appears upon the first charge, but it cannot be recovered during discharge, resulting in the so-called voltage decay. Disappearance of the honeycomb superstructure of the layered structure at a slow C-rate (e.g., 0.1 C) has been proposed to cause the first-cycle voltage decay. By comparing the structural evolution of Li[Li0.2Ni0.2Mn0.6]O2 (LLNMO) at various current densities, the operando synchrotron-based X-ray diffraction results show that the lattice strain in bulk LLNMO is continuously increased over cycling, resulting in the first-cycle voltage loss upon Li-ion insertion. Unlike the LLNMO, the accumulated average lattice strain of LiNi0.8Co0.1Mn0.1O2 (NCM811) and LiNi0.6Co0.2Mn0.2O2 (NCM622) from the open-circuit voltage to 4.8 V could be released on discharge. These findings help to gain a deep understanding of the voltage decay in LMLOs.

Current status and prospect of ZIF-based materials for breast cancer treatment.

Breast cancer, one of the three most life-threatening cancers in modern times, must be explored for treatments with low side effects and practical efficacy. Metal organic framework materials (MOFs) is made by metal ions as the center for point and organic ligands as a bridge connecting a new type of porous nano-materials, among them, the zinc base zeolite imidazole skeleton material series (ZIFs) because of its excellent biocompatibility and pH slow controlled release ability, is widely used in the tumor microenvironment in basic research and achieved remarkable curative effect. Inspired by this, in this review, we focus on the recent research progress on the application of ZIFs in the treatment of breast cancer, mainly studying the structure of ZIFs such as ZIF-8, ZIF-90 and ZIF-67 and their application in novel therapies for breast cancer treatment, such as targeted drug delivery, photothermal therapy, immunotherapy and gene therapy.We will more fully demonstrate the potential of zif in breast cancer treatment, hoping to provide an avenue for exploring breast cancer treatment.

On the follow-up of genome-wide association studies: an overall test for the most promising SNPs.

Even in large-scale genome-wide association studies (GWASs), only a fraction of the true associations are detected at the genome-wide significance level. When few or no associations reach the significance threshold, one strategy is to follow up on the most promising candidates, i.e. the single nucleotide polymorphisms (SNPs) with the smallest association-test P-values, by genotyping them in additional studies. In this communication, we propose an overall test for GWASs that analyzes the SNPs with the most promising P-values simultaneously and therefore allows an early assessment of whether the follow-up of the selected SNPs is likely promising. We theoretically derive the properties of the proposed overall test under the null hypothesis and assess its power based on simulation studies. An application to a GWAS for chronic obstructive pulmonary disease suggests that there are true association signals among the top SNPs and that an additional follow-up study is promising.

Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema.

RATIONALE: chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by specific genetic factors. OBJECTIVES: to identify genetic determinants of emphysema assessed through high-resolution chest computed tomography in individuals with COPD. METHODS: we performed a genome-wide association study (GWAS) of emphysema determined from chest computed tomography scans with a total of 2,380 individuals with COPD in three independent cohorts of white individuals from (1) a cohort from Bergen, Norway, (2) the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and (3) the National Emphysema Treatment Trial (NETT). We tested single-nucleotide polymorphism associations with the presence or absence of emphysema determined by radiologist assessment in two of the three cohorts and a quantitative emphysema trait (percentage of lung voxels less than -950 Hounsfield units) in all three cohorts. MEASUREMENTS AND MAIN RESULTS: we identified association of a single-nucleotide polymorphism in BICD1 with the presence or absence of emphysema (P = 5.2 × 10(-7) with at least mild emphysema vs. control subjects; P = 4.8 × 10(-8) with moderate and more severe emphysema vs. control subjects). CONCLUSIONS: our study suggests that genetic variants in BICD1 are associated with qualitative emphysema in COPD. Variants in BICD1 are associated with length of telomeres, which suggests that a mechanism linked to accelerated aging may be involved in the pathogenesis of emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT00292552).

A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci.

There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of alpha(1)-antitrypsin, which is present in 1-2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the alpha-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48 x 10(-10), (rs8034191) and 5.74 x 10(-10) (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429). The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer.

Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.

Bipolar disorder (BP) is a disabling and often life-threatening disorder that affects approximately 1% of the population worldwide. To identify genetic variants that increase the risk of BP, we genotyped on the Illumina HumanHap550 Beadchip 2,076 bipolar cases and 1,676 controls of European ancestry from the National Institute of Mental Health Human Genetics Initiative Repository, and the Prechter Repository and samples collected in London, Toronto, and Dundee. We imputed SNP genotypes and tested for SNP-BP association in each sample and then performed meta-analysis across samples. The strongest association P value for this 2-study meta-analysis was 2.4 x 10(-6). We next imputed SNP genotypes and tested for SNP-BP association based on the publicly available Affymetrix 500K genotype data from the Wellcome Trust Case Control Consortium for 1,868 BP cases and a reference set of 12,831 individuals. A 3-study meta-analysis of 3,683 nonoverlapping cases and 14,507 extended controls on >2.3 M genotyped and imputed SNPs resulted in 3 chromosomal regions with association P approximately 10(-7): 1p31.1 (no known genes), 3p21 (>25 known genes), and 5q15 (MCTP1). The most strongly associated nonsynonymous SNP rs1042779 (OR = 1.19, P = 1.8 x 10(-7)) is in the ITIH1 gene on chromosome 3, with other strongly associated nonsynonymous SNPs in GNL3, NEK4, and ITIH3. Thus, these chromosomal regions harbor genes implicated in cell cycle, neurogenesis, neuroplasticity, and neurosignaling. In addition, we replicated the reported ANK3 association results for SNP rs10994336 in the nonoverlapping GSK sample (OR = 1.37, P = 0.042). Although these results are promising, analysis of additional samples will be required to confirm that variant(s) in these regions influence BP risk.

Effects of Multimedia Assisted Song Integrated Teaching on College Students' English Learning Interests and Learning Outcomes.

In the process of globalization, the English language not only represents British and American culture, but it has also gradually become a language used all over the world, and it has become essential for many people to learn it as a second language. Education is the century business of a nation. At the same time, to meet the needs of E generation, I generation, and touch-screen generation students, teachers are increasingly undertaking multimedia-integrated curriculum design and instruction. Teachers are no longer knowledge providers, but they are expected to provide students with a personalized learning model and guide and support them in a timely manner. This study included a sample of business students from Guilin University of technology. A total of 216 students participated in a 16-week (3 h per week, a total of 48 h) course of experimental teaching. The research results showed that 1. multimedia assisted, song integrated English teaching affected learning interest, 2. That multimedia assisted, song integrated English teaching affected learning outcomes, and 3. That learning interest had significantly positive effects on learning outcome. Based on these results, this study contributes to improving college students' English listening, speaking, reading, and writing skills via multimedia teaching, which also facilitated their interest and ability to achieve the learning outcomes.

Gene Polymorphisms Associated with Central Precocious Puberty and Hormone Levels in Chinese Girls.

Central precocious puberty (CPP) is associated with adverse health outcomes in females; however, CPP pathogenesis remains unclear. In this study, we investigated the association of 20 single nucleotide polymorphisms (SNPs) in eight genes with CPP risk and hormone levels. A case-control study on 247 and 243 girls with and without CPP, respectively, was conducted at Kunming Children's Hospital, China, from September 2019 to August 2020. The genotype of the SNPs and their haplotypes were identified. Additionally, the effects of the polymorphisms on hormone levels were investigated. Three variants (rs10159082, rs7538038, and rs5780218) in KISS1 and two variants (rs7895833 and rs3758391) in SIRT1 were related to an increased CPP risk (odds ratio (OR) = 1.524, 1.507, 1.409, 1.348, and 1.737; 95% confidence interval (CI) = 1.176-1.974, 1.152-1.970, 1.089-1.824, 1.023-1.777, and 1.242-2.430, respectively). Rs3740051in SIRT1 and rs1544410 in VDR reduced CPP risk (OR = 0.689, 0.464; 95% CI, 0.511-0.928, 0.232-0.925, respectively). Rs1544410, rs7975232, and rs731236 in VDR were negatively correlated with peak follicle-stimulating hormone (FSH; ß = -2.181; P=0.045), basal FSH (ß = -0.391; P=0.010), and insulin-like growth factor (ß = -50.360; P=0.041) levels, respectively. KISS1, SIRT1, and VDR variants were associated with CPP susceptibility, and VDR SNPs influenced hormonal levels in Chinese females with CPP. In particular, VDR polymorphism rs1544410 was associated with both CPP risk and GnRH-stimulated peak FSH levels. Further functional research and large-scale genetic studies of these loci and genes are required to confirm our findings.