Dynamics of a stochastic hepatitis B virus transmission model with media coverage and a case study of China.

Hepatitis B virus (HBV) infection is a global public health problem and there are 257 million people living with chronic HBV infection throughout the world. In this paper, we investigate the dynamics of a stochastic HBV transmission model with media coverage and saturated incidence rate. Firstly, we prove the existence and uniqueness of positive solution for the stochastic model. Then the condition on the extinction of HBV infection is obtained, which implies that media coverage helps to control the disease spread and the noise intensities on the acute and chronic HBV infection play a key role in disease eradication. Furthermore, we verify that the system has a unique stationary distribution under certain conditions, and the disease will prevail from the biological perspective. Numerical simulations are conducted to illustrate our theoretical results intuitively. As a case study, we fit our model to the available hepatitis B data of mainland China from 2005 to 2021.

CKAP4-mediated activation of FOXM1 via phosphorylation pathways regulates malignant behavior of glioblastoma cells.

OBJECTIVE: CKAP4 (Cytoskeleton Associated Protein 4) has been reported as an important regulator of carcinogenesis. A great deal of uncertainty still surrounds the possible molecular mechanism of CKAP4 involvement in GBM. We aimed to specifically elucidate the putative role of CKAP4 in the development of GBM. METHODS: We identified divergent proteomics landscapes of GBM and adjacent normal tissues using mass spectrometry-based label-free quantification. Bioinformatics analysis of differentially expressed proteins (DEPs) led to the identification of CKAP4 as a hub gene. Based on the Chinese Glioma Genome Atlas data, we characterized the elevated expression of CKAP4 in GBM and developed a prognostic model. The influence of CKAP4 on malignant behavior of GBM was detected in vitro and vivo, as well as its downstream target and signaling pathways. RESULTS: The prognosis model displayed accuracy and reliability for the probability of survival of patients with gliomas. CKAP4 knockdown remarkably reduced the malignant potential of GBM cells, whereas its overexpression reversed these effects in GBM cells and xenograft mice. Moreover, we demonstrated that overexpression of CKAP4 leads to increased FOXM1 (Forkhead Box M1) expression in conjunction with an increased level of AKT and ERK phosphorylation. Inhibition of both pathways had synergistic effects, resulting in greater effectiveness of inhibition. CKAP4 could reverse the deregulation of FOXM1 triggered by inhibition of AKT and ERK signaling. CONCLUSIONS: This is the first study to reveal a CKAP4-FOXM1 signaling cascade that contributes to the malignant phenotype of GBMs. The CKAP4-based prognostic model would facilitate individualized treatment decisions for glioma patients.

Integrated Proteomic and N-Glycoproteomic Profiling of Placental Tissues of Patients with Preeclampsia.

Background: Preeclampsia (PE) is a multi-system disorder of pregnancy that poses a serious threat to maternal and perinatal health worldwide. This study aims to evaluate the global alterations of protein expression and N-glycosylations that are crucial for PE pathogenesis. Here, tandem mass tag labeling combined with LC-MS/MS was employed to determine the global expression of all proteins and intact glycopeptide in placentas from three healthy pregnant women, three patients with early-onset severe PE, and three patients with late-onset severe PE. Results: A total of 2260 proteins were quantified across 9 placental tissues, of which 37 and 23 were differentially expressed in the early-onset and late-onset PE groups, compared to the controls. A total of 789 glycopeptides were accurately quantified, which were derived from 204 glycosylated sites in 159 glycoproteins and were modified by 59 N-Linked glycans. A total of 123 differently expressed glycopeptides, which were from 47 glycoproteins were identified among three groups. Through a combined analysis of proteomic and glycoproteomic data, it was found that the changes in 10 glycoproteins were caused by the difference in glycosylation level but not in the protein abundance level. Conclusion: This is the first study to conduct an integrated proteomic and glycoproteomic characterization of placental tissues of PE patients. Our findings suggest that glycosylation modification may affect the molecular function of proteins through changes in the glycosylation structure or the occupancy of glycosylation, which will provide new insights to help elucidating the pathogenic mechanism of PE.

Advances of multiplex ligation-dependent probe amplification technology in molecular diagnostics.

Multiplex ligation-dependent probe amplification (MLPA) is a multiplex copy number analysis tool which is routinely used to detect large mutations in genetic diseases. With continuous modifications, MLPA has been extended for the detection of DNA methylation variation, single nucleotide polymorphisms, chromosome abnormalities and other forms of genomic variation. The combination with other techniques has even enlarged the application of MLPA in molecular diagnostics of various human diseases. In this review, the principle of MLPA-based techniques as well as their main and latest applications in clinical detection are described. It is believed that with improved automation, increased multiplexing, lower cost and the combination with other technologies, MLPA will play an increasingly important role in molecular diagnosis of human disease.

Dynamics of a stochastic COVID-19 epidemic model considering asymptomatic and isolated infected individuals.

Coronavirus disease (COVID-19) has a strong influence on the global public health and economics since the outbreak in 2020. In this paper, we study a stochastic high-dimensional COVID-19 epidemic model which considers asymptomatic and isolated infected individuals. Firstly we prove the existence and uniqueness for positive solution to the stochastic model. Then we obtain the conditions on the extinction of the disease as well as the existence of stationary distribution. It shows that the noise intensity conducted on the asymptomatic infections and infected with symptoms plays an important role in the disease control. Finally numerical simulation is carried out to illustrate the theoretical results, and it is compared with the real data of India.

A novel single-tube multiplex real-time PCR assay for genotyping of thiopurine intolerance-causing variant NUDT15 c.415C>T.

Thiopurines are commonly used in the treatment of acute lymphoblastic leukaemia and autoimmune conditions, can be limited by myelosuppression. The NUDT15 c.415C>T variant is strongly associated with thiopurine-induced myelosuppression, especially in Asians. The purpose of this study was to develop a fast and reliable genotyping method for NUDT15 c.415C>T and investigate the polymorphic distribution among different races in China. A single-tube multiplex real-time PCR assay for NUDT15 c.415C>T genotyping was established using allele-specific TaqMan probes. In 229 samples, the genotyping results obtained through the established method were completely concordant with those obtained by Sanger sequencing. The distributions of NUDT15 c.415C>T among 173 Han Chinese, 48 Miaos, 40 Kazakhs, and 40 Kirghiz were different, with allelic frequencies of 0.06, 0.02, 0.07, and 0, respectively. This method will provide a powerful tool for the implementation of the genotyping-based personalized prescription of thiopurines in clinical settings.

SCN1A IVS5N+5 G>A Polymorphism and Risk of Febrile Seizure and Epilepsy: A Systematic Review and Meta-Analysis.

Background: Previous studies had investigated the association between polymorphism of IVS5N+5 G>A in SCN1A and the risk of febrile seizure and epilepsy. However, the results were inconsistent. We aimed to conduct a systematic review and meta-analysis to evaluate the association between SCN1A IVS5N+5 G>A polymorphism and risk of febrile seizures and epilepsy. Methods: We searched Embase, Medline, Scopus, and CNKI for studies on the association between SCN1A IVS5N+5 G>A polymorphism and risk of febrile seizures and epilepsy up to 19 February 2020. We pooled odds ratios (ORs) and 95% confidence intervals (CIs) by different genetic models. To explore the source of heterogeneity, we performed the subgroup analysis by ethnicity and source of control. Results: We included a total of 12 studies in the meta-analysis. We found a significant negative association between G allele SCN1A IVS5N+5 G>A polymorphism, febrile seizures [G vs. A: OR (95% CI): 0.690 (0.530-0.897); GG vs. AA: 0.503 (0.279-0.908); AG vs. AA: 0.581 (0.460-0.733); GG + AG vs. AA: 0.543 (0.436-0.677); AA + GG vs. AG: 1.309 (1.061-1.615)], and epilepsy [G vs. A: 0.822 (0.750-0.902); GG vs. AA: 0.655 (0.515-0.832); AG vs. AA: 0.780 (0.705-0.862); GG vs. AG + AA: 0.769 (0.625-0.947); GG + AG vs. AA: 0.743 (0.663-0.833); AA + GG vs. AG: 1.093 (1.001-1.193)]. The subgroup analysis shows the association varied by type of disease, ethnicity, and source of control. Conclusion: The present meta-analysis suggests that G allele in SCN1A IVS5N+5 G>A polymorphism is a protective factor of febrile seizures and epilepsy. It is possible to determine the vulnerability of each individual to develop febrile seizures or epilepsy genotype by these genetic variants. Future studies with better study designs are needed to confirm the results. Study Registration: This study was registered in the International Prospective register of systematic reviews (PROSPERO, CRD42020163318).

Global dynamics and bifurcation analysis of a host-parasitoid model with strong Allee effect.

In this paper, we study the global dynamics and bifurcations of a two-dimensional discrete time host-parasitoid model with strong Allee effect. The existence of fixed points and their stability are analysed in all allowed parametric region. The bifurcation analysis shows that the model can undergo fold bifurcation and Neimark-Sacker bifurcation. As the parameters vary in a small neighbourhood of the Neimark-Sacker bifurcation condition, the unique positive fixed point changes its stability and an invariant closed circle bifurcates from the positive fixed point. From the viewpoint of biology, the invariant closed curve corresponds to the periodic or quasi-periodic oscillations between host and parasitoid populations. Furthermore, it is proved that all solutions of this model are bounded, and there exist some values of the parameters such that the model has a global attractor. These theoretical results reveal the complex dynamics of the present model.

Nitric oxide mediated effects on reproductive toxicity caused by carbon disulfide in male rats.

This study investigated nitric oxide (NO) mediation of carbon disulfide (CS(2)) toxicity that compromised male rat spermatogenesis and endocrine function. Rats were exposed to multiple levels of CS(2) concentration (0, 50, 250, 1250 mg/m(3)). A 1250 mg/m(3) CS(2)+sodium nitroprusside (SNP) group and a 1250 mg/m(3) CS(2)+NG-monomethyl-L-arginine (L-NMMA) group were established to explore the role of NO in mediating CS(2) toxicity. NO concentrations, NO synthase (NOS) activity, and sex hormone levels were measured, and sperm characteristics were observed and analyzed. Our data show that CS(2) exposure decreased: NOS activity; tissue NO concentrations; serum levels of gonadotropin-releasing hormones, luteinizing hormones, and testosterone; and sperm count and activity. In contrast, increased serum follicle-stimulating hormone concentrations and teratospermia were observed with CS(2) exposure. SNP reduced some of the toxic effects of CS(2), while L-NMMA treatment showed no effect. The results suggests that NO mediates compromised reproductive system function caused by CS(2) exposure.

The effects of carbon disulfide on male sexual function and semen quality.

A cross-sectional study was initiated to clarify whether the current level of exposure to carbon disulphide (CS(2)) is low enough to prevent occurrence of subclinical health impairments. This paper describes the effects of exposure to CS(2) on male sexual function and semen quality in a baseline observation. The effects of CS(2) on male sexual function were evaluated, including number of sexual encounters and length of sexual encounters related to solvents in 80 male workers exposed to CS(2) and 49 reference workers from the filature and cotton pulp departments of a fabric factory in China. And the semen samples were obtained from 43 of the exposed and 35 of the control. Adjustment was made for potential confounding factors such as age or alcohol drinking. Exposure to CS(2) was dichotomized by job type. The rate of sexual dysfunction was higher, number of sexual encounters was lower, and length of sexual encounters was shorter compared with the control (p < 0.001). It was indicated that exposed workers had fewer semen quantity, longer liquefaction time, lower acrosomal membrane integrity rate, vitality and density, and more deformity of semen than the control (p < 0.01). The age and type of work played the most important roles in sexual dysfunction by the multinomial logistic regression analysis (p < 0.01).The duration of exposure had the effect on sexual function and semen quality but no statistical significance (p > 0.05). Clinical effects on the male sexual function and semen quality were found in the workers exposed to CS(2).