GLP-1 plays a protective role in hippocampal neuronal cells by activating cAMP-CREB-BDNF signaling pathway against CORT+HG-induced toxicity.

Major depressive disorder (MDD) with diabetes mellitus (DM) significantly reduces the quality of the patient's life, and currently, there is no effective treatment. This study explored the feasibility of Glucagon-like peptide-1 (GLP-1) in treating MDD combined with DM. The protective effects of GLP-1 on mouse hippocampal neuronal cell line HT22 cultured with corticosterone (CORT) and high glucose (HG) were assessed. HT22 cells were cultured with CORT + HG to construct a cell model of MDD combined with DM. Cell viability and cell apoptosis/necrocytosis were detected by CCK-8 assay and flow cytometry/confocal laser scanning microscopy, respectively, after treatment with GLP-1. In addition, BDNF and neurotransmitter levels, lactic dehydrogenase (LDH) and glucose levels, and proteins of cAMP-CREB-BDNF signal pathway in the culture supernatants were measured through an enzyme-linked immunosorbent assay and colorimetric assays and Western blot, respectively. The ideal intervention combination to construct a cell model of MDD combined with DM was CORT 200 µM and HG 50 mM for 48 h. After treatment of 50 nM GLP-1 for 48 h, the model+50 nM GLP-1 group's apoptosis and necrocytosis rates and LDH and glucose concentrations in the culture supernatants decreased significantly compared with the model group. However, the BDNF, 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), PKA, p-CREB, and p-Trkb concentrations in the culture supernatants increased significantly. GLP-1 functioned against CORT + HG-induced toxicity by activating the cAMP-CREB-BDNF signaling pathway in hippocampal neuronal cells.

Correlation between intestinal glucagon-like peptides-1 and major depressive disorder / 中华行为医学与脑科学杂志

Objective:To explore the pathogenesis of major depressive disorder(MDD) by comparing the serum glucose and lipid metabolism indicators, levels of glucagon-like peptide-1(GLP-1) in plasma and feces, and the content of specific intestinal flora ( Lactobacillus, Bifidobacterium) between patients with MDD who were diagnosed for the first time and healthy controls. Methods:Totally 80 MDD patients hospitalized from January 1, 2020 to March 30, 2021 and 80 healthy volunteers with normal physical examination in the same period were selected. Blood and fecal samples of patients with MDD and healthy controls were collected respectively. The indicators of serum glucose and lipid metabolism were detected by automatic biochemical analyzer, the concentrations of GLP-1 in plasma and feces were detected by ELISA, and the relative contents of Lactobacillus and Bifidobacterium in feces were detected by real-time PCR. The differences between two groups of glucose and lipid metabolism indicators, GLP-1 levels and the relative contents of Lactobacillus and Bifidobacterium in feces were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and analysis of variance were used for inter group comparison, and Pearson correlation analysis was used for correlation analysis. Results:Compared with the control group, the levels of serum TC, HDL, and LDL in the MDD group decreased ((3.99±0.85)mmol/L , (4.78±0.86)mmol/L; (1.18±0.29)mmol/L, (1.30±0.28)mmol/L; (2.64±0.70)mmol/L, (3.19±0.69)mmol/L; t=5.559, 2.371, 4.695, all P<0.05). The plasma and fecal GLP-1 levels of the MDD group were lower than those of the control group (plasma: (0.81±0.22)pmol/mL, (1.05±0.26)pmol/mL , t=4.509, P<0.01; feces: (2.23±0.46)pmol/mL , (2.47±0.37)pmol/mL, t=2.533, P<0.05). Compared with the control group, the relative contents of Lactobacillus(2.56±1.59, 3.51±2.21) and Bifidobacterium(2.24±1.89 , 3.17±2.08) in the MDD group decreased ( t=2.218, 2.082, both P<0.05). The level of plasma GLP-1 in the MDD group was negatively correlated with FPG, TG, and disease severity ( r=-0.281, -0.221, -0.437, P<0.05). The level of plasma GLP-1 in the control group was negatively correlated with FPG ( r=-0.580, P<0.01). The fecal GLP-1 level of the MDD group was negatively correlated with the severity of the disease ( r=-0.298, P<0.01), and the fecal GLP-1 level of the control group was positively correlated with fecal Lactobacillus and Bifidobacterium ( r=0.685, 0.428, P<0.01). Conclusion:MDD patients have abnormal glucose and lipid metabolism, decreased GLP-1 level and decreased relative content of intestinal Lactobacillus and Bifidobacterium. Changes in intestinal flora affect GLP-1 levels. GLP-1 can affect glucose and lipid metabolism and depressive symptoms in patients with MDD by binding to specific receptors in intestinal tract and central nervous system.

Insight into skywave theory and breakthrough applications in resource exploration.

Skywave refers to the electromagnetic wave reflected or refracted from the ionosphere and propagated in the form of a guided wave between the ionosphere and the Earth's surface. Since the skywave can propagate over large distances, it has been widely used in long-distance communication. This paper explores and demonstrates the feasibility of skywave for deep resource and energy exploration at depths of up to 10 km. Theoretical and technical advancements were accomplished in furthering skywave applications. A new solution method based on Green's function has been developed to study skywave propagation in a fully coupled lithosphere-air-ionosphere full space model. For the first time, the model allows one to study skywave distribution characteristics in the lithosphere containing inhomogeneity such as ore deposits or oil and gas reservoirs. This model also lays a foundation for skywave data processing and interpretation. On a parallel line, we have developed a multi-channel, broadband, low-noise, portable data acquisition system suitable for receiving skywave signals. Using the skywave field excited by a high-power fixed source located in central China, actual field surveys have been carried out in some areas in China including the Biyang depression of Henan Province. The initial results appear encouraging-the interpreted resistivity models prove to be consistent with those of seismic exploration and known geological information, and the exploration cost is only ∼1/4 to 1/10 that of seismic surveys. These initial successful applications of the skywave theory lay a solid foundation for further verification of the new method.

Effects of Process Parameters on the Thickness Uniformity in Two-Point Incremental Forming (TPIF) with a Positive Die for an Irregular Stepped Part.

Incremental sheet forming (ISF) is a novel flexible forming technology with advantages, such as a low forming force, low-energy-consuming equipment, and good forming performance. The lack of available information about the formability of the two-point incremental forming (TPIF) process makes it limited for practical applications. Taking an irregular stepped part as the target part, the effects of process parameters on the thickness uniformity when using TPIF with a positive die for AA1060 aluminum alloy sheets were investigated. First, the set of optimal parameters regarding the diameter of the tool head, feed rate, and the step size were obtained through orthogonal experiments. Furthermore, the optimal parameter set of the number of forming passes, the direction of movement of the forming tool, and the forming angle was determined and the optimal forming result was numerically and experimentally verified. This demonstrated that the parameters affecting the thickness uniformity of the irregular stepped parts were, in descending order, the diameter of the forming tool, the feed rate, and the step size, with corresponding optimal values of 12 mm, 15,000 mm/min, and 0.4 mm, respectively. With an increase of the number of passes and a decrease of the forming angle between adjacent passes, and adopting an alternating clockwise and counterclockwise toolpath, the thickness uniformity of the formed parts was effectively improved.

The association between rs12807809 polymorphism in neurogranin gene and risk of schizophrenia: A meta-analysis.

BACKGROUND: The correlation between single nucleotide polymorphism (SNP) rs12807809 in Neurogranin (NRGN) gene and Schizophrenia (SCZ) was investigated by several studies, whereas the results were conflicting. Thus, we performed the present meta-analysis to combine and analyze the available studies in order to provide a more accurate result on the association of rs12807809 polymorphism in NRGN gene and SCZ vulnerability. METHODS: A comprehensive retrieval in PubMed, EMBASE, Web of Science, Cochrane Library and Wanfang was performed for relevant studies on the relationship of rs12807809 polymorphism and SCZ. Summary odds ratios (OR) with 95% confidence interval (95% CI) were calculated in allelic, homozygous, heterozygous, dominant and recessive model to appraise the association. RESULTS: The meta-analysis included 8 studies containing 12552 SCZ cases and 34783 controls. The results showed a statistically significant correlation between SCZ and rs12807809 polymorphism in overall population in allelic model (OR = 1.10, 95%CI 1.04-1.17). However, subgroup analysis indicated the association only existed in Caucasians but not Asian. CONCLUSION: The results of present meta-analysis suggested significant association between SNP rs12807809 in NRGN gene and SCZ susceptibility in Caucasians but not Asians.

Achieving High Strength and Good Ductility in As-Extruded Mg-Gd-Y-Zn Alloys by Ce Micro-Alloying.

In this study, the effect of Ce additions on microstructure evolution of Mg-7Gd-3.5Y-0.3Zn (wt %) alloys during the casting, homogenization, aging and extrusion processing are investigated, and novel mechanical properties are also obtained. The results show that Ce addition promotes the formation of long period stacking ordered (LPSO) phases in the as-cast Mg-Gd-Y-Zn-Ce alloys. A high content of Ce addition would reduce the maximum solubility of Gd and Y in the Mg matrix, which leads to the higher density of Mg12Ce phases in the as-homogenized alloys. The major second phases observed in the as-extruded alloys are micron-sized bulk LPSO phases, nano-sized stripe LPSO phases, and broken Mg12Ce and Mg5RE phases. Recrystallized grain size of the as-extruded 0.2Ce, 0.5Ce and 1.0Ce alloys can be refined to ~4.3 µm, ~1.0 µm and ~8.4 µm, respectively, which is caused by the synthesized effect of both micron phases and nano phases. The strength and ductility of as-extruded samples firstly increase and then decrease with increasing Ce content. As-extruded 0.5Ce alloy exhibits optimal mechanical properties, with ultimate strength of 365 MPa and ductility of ~15% simultaneously.

Association between CMYA5 gene polymorphisms and risk of schizophrenia in Uygur population and a meta-analysis.

AIM: Previous evidence has found that some single nucleotide polymorphisms (SNPs) in cardiomyopathy-associated 5 gene (CMYA5) were associated with schizophrenia in the Caucasian and Chinese Han populations. In this study, we aimed to investigate the relationship between CMYA5 gene polymorphisms and schizophrenia in Chinese Uygur population and perform a meta-analysis to synthetically analyse the association of CMYA5 gene polymorphisms with schizophrenia in Asian populations. METHOD: We retrospectively analysed 985 schizophrenia cases and 1123 healthy controls in Chinese Uygur population. Four SNPs (rs259127, rs3828611, rs4704591 and rs6883197) of CMYA5 were genotyped using TaqMan SNP genotyping assay. Meta-analysis was conducted across Asian studies by Review Manager 5.2. RESULTS: Results showed no significant difference in either allelic or genotypic frequency in four SNPs of the CMYA5 gene between cases and controls (P > 0.05). However, the age of onset and the PANSS positive-factor subscale score were significantly lower in schizophrenia patients with the A/A genotype of rs6883197 than those with A/G and G/G genotypes (P < 0.05). In addition, the meta-analysis showed the significant association of rs3828611 with risk of schizophrenia (P = 0.03, OR = 0.92, 95% CI: 0.91-0.99). CONCLUSIONS: Our results support the association between CMYA5 rs6883197 and schizophrenia in Chinese Uygur population. Meta-analysis demonstrated that rs3828611 was significantly associated with schizophrenia in Asian population. Genetic heterogeneity among populations may be the main reason of results conflict between studies. In conclusion, association between CMYA5 gene polymorphisms and schizophrenia was confirmed in Asian population.

Case control study of association between the ANK3 rs10761482 polymorphism and schizophrenia in persons of Uyghur nationality living in Xinjiang China.

BACKGROUND: The rs10761482 polymorphism of the ANK3 gene has been associated with the occurrence of schizophrenia. AIM: Assess the relationship between the ANK3 gene and schizophrenia in individuals of Uyghurian descent. METHODS: A total of 630 patients with schizophrenia and 535 healthy controls of Uyghur descent were genotyped for the ANK3 gene rs10761482 locus using Taqman probe technology. SHEsis and SPSS17.0 software were used for data analysis. RESULTS: There were no significant differences in the genotype or allele frequencies between the case group and control group. Within the case group there was no relationship between gender or age of onset of schizophrenia and the genotype or allele frequencies. Separate analyses among men and among women also failed to identify significant differences in the allele and genotype frequencies between cases and controls or between patients with adolescent-onset schizophrenia and those with adult-onset schizophrenia. CONCLUSION: Our findings do not support previous reports about the relationship of the ANK3 gene and schizophrenia. In the Uyghur nationality group recruited for this study there was no significant association between the ANK3 gene rs10761482 polymorphism and schizophrenia. If these results are replicated in further studies, then the focus should change to understanding why this widely acknowledged association does not exist in this particular ethnic group.

CACNA1C, schizophrenia and major depressive disorder in the Han Chinese population.

BACKGROUND: Common psychiatric disorders are highly heritable, indicating that genetic factors play an important role in their aetiology. The CACNA1C gene, which codes for subunit alpha-1C of the Cav1.2 voltage-dependent L-type calcium channel, has been consistently found to be the shared risk gene for several kinds of mental disorder. AIMS: To investigate whether CACNA1C is a susceptibility gene for schizophrenia and major depressive disorder in the Han Chinese population. METHOD: We carried out a case-control study of 1235 patients with schizophrenia, 1045 with major depressive disorder and 1235 healthy controls. A tag single nucleotide polymorphism (SNP) rs1006737 along with another 10 tag SNPs in the CACNA1C gene were genotyped in all samples. RESULTS: We found that rs1006737 was associated with both schizophrenia (P(allele) = 0.0014, P(genotype) = 0.006, odds ratio (OR) = 1.384, 95% CI 1.134-1.690) and major depressive disorder (P(allele) = 0.0007, P(genotype) = 0.003, OR = 1.425, 95% CI 1.160-1.752). CONCLUSIONS: Our findings support CACNA1C being a risk gene for both schizophrenia and major depressive disorder in the Han Chinese population.

Association analysis of the GRM8 gene with schizophrenia in the Uygur Chinese population.

GRM8 is a schizophrenia candidate gene that is also thought to be involved in the glutamate pathway, which is very important in the pathogenesis of schizophrenia. In this study, we aim to investigate the association between GRM8 and schizophrenia in the Uygur Chinese population. Rs2237748 and rs2299472, located in the GRM8 gene, were selected for genotyping in a set of Uygur Chinese case-control samples, which included 723 cases and 561 controls, using TaqMan assays and capillary sequencing. The statistical analysis was carried out using the online software program SHEsis, and a meta-analysis was carried out to identify other relevant studies using Review Manager 5. We found that the rs2299472 genotype was significantly associated with schizophrenia (P = 0.015, P = 0.030, after Bonferroni correction). The frequency of the CC genotype was higher in the schizophrenic patients (P = 0.008), and the frequency of the AC genotype was lower (P = 0.008). Furthermore, the meta-analysis incorporating the previous and current studies also showed that rs2299472 is associated with schizophrenia. This study indicates that the GRM8 gene may play an important role in the pathogenesis of schizophrenia.

CNTNAP2 is significantly associated with schizophrenia and major depression in the Han Chinese population.

CNTNAP2, located on 7q35-36.1, encodes a single-pass transmembrane protein mediating cell-cell interactions in the nervous system. CNTNAP2 has been suggested to play an important role in mental diseases such as autism and language disorder. However, we still do not know whether it also confers risk to major psychiatric disorders such as schizophrenia, major depression and bipolar disorder. We analysed single nucleotide polymorphisms (SNPs) previously reported to be associated with autism or language impairment in 1135 schizophrenia patients, 1135 unrelated major depression patients, 1135 unrelated bipolar disorder patients and 1135 unrelated normal controls recruited from the Han Chinese population. We found that the genotypes of rs17236239 were significantly associated with schizophrenia and the alleles of rs2710102 and rs2710117 were significantly associated with major depression. According to the location of significant signals, our study indicated that exon 13-15 of CNTNAP2 may play important roles in both schizophrenia and major depression in the Han Chinese population.

Reactive gingival lesions: a retrospective study of 2,439 cases.

OBJECTIVE: To identify the clinicopathologic features of epulides in West China and to compare these data with those of previous studies from other countries. METHOD AND MATERIALS: Demographics; clinical data including gender, age, and chief complaints of the patients; and the type, size and location, duration, diagnosis, and histologic features of the lesion were studied from among biopsy specimens and clinical records at West China College of Stomatology from January 1951 to July 2005. RESULTS: A total of 2,439 epulides were identified. Epulides found were peripheral fibroma (PF: 1,489, 61.05%), peripheral ossifying fibroma (POF: 431, 17.67%), pyogenic granuloma (PG: 482, 19.76%), and peripheral giant cell granuloma (PGCG: 37, 1.52%). The total ratio of males to females was 1:1.40. Specifically, the ratios were 1:1.31 for PF, 1:1.99 for PG, and 1:1.47 for PGCG (all P < .001). The peak incidence of epulides fell in the third to sixth decade of life overall, the fifth to sixth decade for PF and POF, and the third to fourth decade for PG. CONCLUSIONS: Among the 4 kinds of reactive lesions, PF had the highest incidence and PG had the lowest incidence in Chinese patients. There were also differences in type, sex, age, location, duration, and histologic features: PF was the most common type; all of the epulides except PGCG showed a predilection for females; PG was more prevalent among young patients; and POF lasted much longer than other lesions. Differences in the distribution of the 4 types of lesion were also found among various ethnic groups.