Genetic factors related to the regulation of apoptosis in schizophrenia patients may be involved in a reduced vulnerability to cancer. XRCC4 is one of the potential candidate genes associated with schizophrenia which might induce colorectal cancer resistance.

The 14-3-3 family, which is composed of seven distinct members in humans, plays important roles in the cell cycle, apoptosis, synaptic plasticity and neuronal differentiation and migration. Previous genetic and post-mortem gene expression studies have linked this family to schizophrenia. However, the direction of gene expression changes in these studies has been inconsistent, and reports of 14-3-3 gene expression in living schizophrenic patients are still lacking. Here, we assessed 14-3-3 gene and protein expression levels in peripheral blood leukocytes from drug-naïve first-episode schizophrenic patients and matched controls. mRNA and protein expression levels were quantified by qRT-PCR and UPLC-MRM/MS, respectively. Expression analysis revealed four downregulated and one upregulated mRNA transcripts as well as five downregulated protein levels of 14-3-3 isoforms in schizophrenia. Moreover, significant positive correlations between 14-3-3 mRNA and protein expression levels were found in schizophrenia, and we also identified negative correlations between ε, θ and ζ isoform expression levels and positive symptoms of schizophrenia. Our results suggest that gene and protein expression levels for the 14-3-3 family are dysregulated in schizophrenia, perhaps owing to specific regulatory mechanisms, and we also suggest that expression of the 14-3-3ε, θ and ζ isoform genes could be useful indicators of disease severity.

Agitation is very common in patients with acute stage schizophrenia, and injection of antipsychotics and clonazepam is widely used. Network meta-analysis of these comparisons among three injection treatments has been seldom reported.

Pioglitazone was used to treat patients of PCOS in many researches, but the treatment has not been recognized by public or recommended by all the guidelines.

Myocardial infarction (MI), characterized by interruption of blood and oxygen to myocardium, is a common yet fatal cardiovascular event that causes progressive damage to myocardial tissue and eventually leads to heart failure. Previous studies have shown increased expression of microRNA-223 (miR-223) in infarcted myocardial tissues of humans and in rat models of MI. However, the role of miR-223 in cell survival during MI has not been elucidated. Thus, we aimed to investigate whether miR-223 participates in the regulation of cardiac ischemia-induced injury and to elucidate the underlying mechanisms of this process. qRT-PCR revealed that miR-223 expression levels are significantly upregulated in the myocardial tissues of rats with post-MI heart failure and in hypoxia-treated neonatal rat cardiomyocytes (NRCMs) and H9c2 cells, which indicates that miR-223 may be associated with chronic ischemia. We also transfected NRCMs and H9c2 cells with miR-223 mimics or inhibitors in vitro, and the results revealed that increasing miR-223 expression protected cells from hypoxia-induced apoptosis and excessive autophagy, whereas decreasing miR-223 expression had contrasting effects. Further exploration of the mechanism showed that poly(ADP-ribose) polymerase 1 (PARP-1) is a target gene of miR-223 and that silencing PARP-1 prevented hypoxia-induced cell injury; additionally, silencing PARP-1 blocked the aggravated impact of miR-223 inhibitors. Thus, PARP-1 mediates the protective effects of miR-223 in hypoxia-treated cardiomyocytes. We also investigated the involvement of the Akt/mTOR pathway in the above phenomena. We found that miR-223 overexpression and PARP-1 silencing positively regulated the Akt/mTOR pathway and that treating cells with NVP-BEZ235 (BEZ235), a novel dual Akt/mTOR inhibitor, could reverse the inhibitory effects of both the miR-223 mimics and PARP-1 siRNA on hypoxia-induced apoptosis and autophagy. Taken together, our findings showed that miR-223 protects NRCMs and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1; thus, miR-223 may be a potential target in the treatment of MI in the future.

Despite there is a wide range of antidepressants available, with various mechanisms of actions, the efficacy of current therapeutic options is yet satisfactory. Previous shreds of evidence have indicated that genetics, cognitive, neuroendocrine, as well as personality factors, are all intrinsically linked and contribute to the diversity of treatment outcomes. We, therefore, sought to investigate this hypothesis in this study.

In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provide a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain of the viral Spike (S) glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic viral infection in a standard 96-h co-incubation assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.

This study was intended to ascertain whether SNPs in dopaminergic and serotoninergic pathway genes SLC6A2, SLC6A3 and DRD2 are associated with schizophrenia in Han Chinese people. We conducted a case-control study by genotyping 7 SNPs of the three genes in 1034 schizophrenia patients and 1034 controls. No significant difference in the allelic or genotypic frequency was detected between cases and controls despite one positive haplotype (rs1362621-rs2242446-rs5564). Stratified analysis of gender and gene-gene interaction analysis showed no positive results. In summary, our study denies the major role of these SNPs within the three genes for schizophrenia in Han Chinese.

Peroxiredoxin (Prx, EC 1.11.1.15) is a family of the thiol-dependent antioxidant enzyme. In this study, a cold-adapted Prx gene from Antarctic psychrophilic bacterium Psychrobacter sp. ANT206 (PsPrx) consisted of an open reading frame (ORF) of 567 bp was cloned. Amino acid sequence analysis revealed that PsPrx contained one catalytic site (Thr45, Cys48 and Arg121) and could be categorized as a typical 2-Cys Prx. Compared with the mesophilic StPrx, PsPrx with a reduced amount of hydrogen bonds and salt bridges and other characteristics, may be responsible for its enzymatic stability and flexibility at low temperature. The recombinant PsPrx (rPsPrx) was purified to homogeneity by Ni-NTA and its enzymatic characterization was described. Interestingly, rPsPrx exhibited the maximum activity at 30 °C and remained 42.6% of its maximum activity at 0 °C. rPsPrx was a salt-tolerance enzyme that showed 42.2% of its maximum activity under 2.5 M NaCl. The kinetic parameters of different substrates revealed that it could efficiently catalyze the peroxides, especially H2O2 and t-BOOH (tert‑butyl hydroperoxide). Moreover, rPsPrx exhibited the ability to protect super-coiled DNA from oxidative damage. These results indicated that rPsPrx has special catalytic properties and may be a promising candidate for food and industrial applications.

Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism.

The COVID-19 is creating panic among people around the world and is causing a huge public mental health crisis. Large numbers of observational studies focused on the prevalence of psychological problems during the COVID-19 pandemic were published. It is essential to conduct a meta-analysis of the prevalence of different psychological statuses to insight the psychological reactions of general population during the COVID-19 epidemic in China. Sixty six observational studies about the psychological statuses of people during the COVID-19 were included, searching up to 1 December 2020. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) was used to evaluate the quality of the included studies. OpenMeta[Analyst] was used for the data analysis. High prevalence of acute stress and fear symptoms were observed in the early period of the epidemic. Additionally, anxiety and depression symptoms continued at a high prevalence rate during the epidemic. It should alert the lasting mental health problems and the risk of post-traumatic stress disorder and other mental disorders. Systematic Review Registration: PROSPERO CRD 42020171485.

Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN).

DiGeorge Syndrome Critical Region Gene 8 (DGCR8) is a key component of the microprocessor complex governing the maturation of most microRNAs, some of which participate in schizophrenia and neural development. Previous studies have found that the 22q11.2 locus, containing DGCR8, confers a risk of schizophrenia. However, the role of DGCR8 in schizophrenia and the early stage of neural development has remained unknown. In the present study, we try to identify the role of DGCR8 in schizophrenia from human samples and animal models. We found that the G allele and GG genotype of rs3757 in DGCR8 conferred a higher risk of schizophrenia, which likely resulted from higher expression of DGCR8 according to our test of dual-luciferase reporter system. Employed overexpression model in utero and adult mice, we also revealed that the aberrant increase of Dgcr8 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice. Together, these results demonstrate that DGCR8 may play a role in the etiology of schizophrenia through regulating neural development.

Phage peptide display is a powerful technique for discovery of various target-specific ligands. However, target-unrelated peptides can often be obtained and cause ambiguous results. Peptide PB-TUP has been isolated repeatedly in our laboratory on different targets and we conducted a research on PB-TUP phage to investigate their binding properties and rate of propagation. ELISA and phage recovery assay demonstrated that PB-TUP phage had a significant superior affinity to polystyrene solid surface compared with control phage clones. In this study, some incidental bindings are excluded like blocking agents and non-specific binding of secondary antibodies. Propagation rate assays of the selected phage clones showed that the growth rate of PB-TUP phage was not superior to the control phages. Furthermore, the binding of PB-TUB to polystyrene was concentration dependent and varied with solution pH. Molecular modeling revealed that stable structures of α-helix and β-turn may contribute to the binding of PB-TUP to polystyrene plate. The PB-TUP sequence was fused to the N-terminus of peptide P2 and the fusion peptide significantly increased the binding affinity to polystyrene. The fusion peptide also enhanced the cell adhesion ability of peptide P2 with human umbilical vein endothelial cell (HUVEC). The addition of the polystyrene binding peptide provided a convenient method for peptide immobilization.

The expression level of folate receptor alpha (FRα) is located highly rate in ovarian cancer though it is remained absent in normal tissues. This highly tumor restricted expression profile makes FRα a promising target for tumor therapy and diagnosis. In this research we report a FRα binding peptide C7(Met-His-Thr-Ala-Pro-Gly-Trp-Gly-Tyr-Arg-Leu-Ser) discovered by phage display and this peptide showed specific binding to FRα expressing cells by cell ELISA and flow cytometry. Tumor targeting ability of C7 was proved in vivo by both phage homing experiment and fluorescence imaging. C7 can be internalized by SKOV3 cells and its affinity to FRα was determined by MST. The molecular recognition was revealed by structure modeling, suggesting its binding mode with FRα.

Electroconvulsive therapy (ECT) is an effective therapy for major depressive disorder (MDD) patients. However, few clinical predictors are available to predict the treatment outcome. This study aimed to characterize the response trajectories of MDD patients undergoing ECT treatment and to identify potential clinical and demographic predictors for clinical improvement.

Recently, increasing attention has been paid to the periodontal health of orthodontic patients in the maintenance stage in clinical practice. The focus of this meta-analysis was to compare the effects of vacuum-formed retainers (VFR) and Hawley retainers (HR) on periodontal health, in order to provide a reference for clinical selection.

The discovery of checkpoint inhibitors towards cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has been revolutionary for the treatment of cancers. These therapies have only offered an average of 20%-30% response rates across the tumor spectrum and the combination of agonists towards the tumor-necrosis superfamily members, such as 4-1BB and CD40, has shown potent efficacy in preclinical studies; however, these agonists have exhibited high degrees of toxicity with limited efficacy in human trials. In this study, we have generated a single-domain antibody towards a unique epitope of 4-1BB that limits its potential on-target toxicity while maintaining sufficient potency. This 4-1BB binder is ideal for use in the engineering of multispecific antibodies to localize 4-1BB activation within the tumor microenvironment, as shown here by a anti-PD-L1/4-1BB bispecific candidate (PM1003).

The association between dietary patterns and depression has gained significant attention, but the relationship between fruit intake and depression remains unclear. This study aimed to investigate the role of fruit intake in the risk of depression using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR) analysis, and further explore the causal relationship between them.

Production of haploid gametes from diploid progenitor cells is mediated by a specialized cell division, meiosis, where two divisions, meiosis I and II, follow a single S phase. Errors in progression from meiosis I to meiosis II lead to aneuploid and polyploid gametes, but the regulatory mechanisms controlling this transition are poorly understood. Here, we demonstrate that the conserved kinase Ime2 regulates the timing and order of the meiotic divisions by controlling translation. Ime2 coordinates translational activation of a cluster of genes at the meiosis I-meiosis II transition, including the critical determinant of the meiotic chromosome segregation pattern CLB3. We further show that Ime2 mediates translational control through the meiosis-specific RNA-binding protein Rim4. Rim4 inhibits translation of CLB3 during meiosis I by interacting with the 5' untranslated region (UTR) of CLB3. At the onset of meiosis II, Ime2 kinase activity rises and triggers a decrease in Rim4 protein levels, thereby alleviating translational repression. Our results elucidate a novel developmentally regulated translational control pathway that establishes the meiotic chromosome segregation pattern.