Downregulation of peripheral luteinizing hormone rescues ovariectomy-associated cognitive deficits in APP/PS1 mice.

Alzheimer's disease (AD) is more prevalent in women than men, supposing due to the decline of estrogens in menopause, accompanied by increased gonadotropins such as luteinizing hormone (LH). We and others found that the transcription factor early growth response-1 (EGR1) regulates cholinergic function including the expression of acetylcholinesterase (AChE) and plays a significant role in cognitive decline of AD. Here we investigated in APP/PS1 mice by ovariectomy (OVX) and estradiol (E2) supplementation or inhibition of LH the effect on hippocampus-related cognition and related molecular changes. We found that OVX-associated cognitive impairment was accompanied by increased dorsal hippocampal EGR1 expression, which was rescued by downregulating peripheral LH rather than by supplementing E2. We also found in postmortem AD brains a higher expression of pituitary LH-mRNA and higher EGR1 expression in the posterior hippocampus. Both, in human and mice, there was a significant positive correlation between respectively posterior/dorsal hippocampal EGR1 and peripheral LH expression. We conclude that peripheral increased LH and increased posterior hippocampal EGR1 plays a significant role in AD pathology.

Modifying the amino acids in conformational motion pathway of the α-amylase of Geobacillus stearothermophilus improved its activity and stability.

Amino acids along the conformational motion pathway of the enzyme molecule correlated to its flexibility and rigidity. To enhance the enzyme activity and thermal stability, the motion pathway of Geobacillus stearothermophilus α-amylase has been identified and molecularly modified by using the neural relational inference model and deep learning tool. The significant differences in substrate specificity, enzymatic kinetics, optimal temperature, and thermal stability were observed among the mutants with modified amino acids along the pathway. Mutants especially the P44E demonstrated enhanced hydrolytic activity and catalytic efficiency (kcat/KM) than the wild-type enzyme to 95.0% and 93.8% respectively, with the optimum temperature increased to 90°C. This mutation from proline to glutamic acid has increased the number and the radius of the bottleneck of the channels, which might facilitate transporting large starch substrates into the enzyme. The mutation could also optimize the hydrogen bonding network of the catalytic center, and diminish the spatial hindering to the substrate entry and exit from the catalytic center.

Brain-wide changes in excitation-inhibition balance of major depressive disorder: a systematic review of topographic patterns of GABA- and glutamatergic alterations.

The excitation-inhibition (E/I) imbalance is an important molecular pathological feature of major depressive disorder (MDD) as altered GABA and glutamate levels have been found in multiple brain regions in patients. Healthy subjects show topographic organization of the E/I balance (EIB) across various brain regions. We here raise the question of whether such EIB topography is altered in MDD. Therefore, we systematically review the gene and protein expressions of inhibitory GABAergic and excitatory glutamatergic signaling-related molecules in postmortem MDD brain studies as proxies for EIB topography. Searches were conducted through PubMed and 45 research articles were finally included. We found: i) brain-wide GABA- and glutamatergic alterations; ii) attenuated GABAergic with enhanced glutamatergic signaling in the cortical-subcortical limbic system; iii) that GABAergic signaling is decreased in regions comprising the default mode network (DMN) while it is increased in lateral prefrontal cortex (LPFC). These together demonstrate abnormal GABA- and glutamatergic signaling-based EIB topographies in MDD. This enhances our pathophysiological understanding of MDD and carries important therapeutic implications for stimulation treatment.

F-box and leucine-rich repeat 6 promotes gastric cancer progression via the promotion of epithelial-mesenchymal transition.

BACKGROUND: F-box and leucine-rich repeat 6 (FBXL6) have reportedly been associated with several cancer types. However, the role and mechanisms of FBXL6 in gastric cancer (GC) require further elucidation. AIM: To investigate the effect of FBXL6 in GC tissues and cells and the underlying mechanisms. METHODS: TCGA and GEO database analysis was performed to evaluate the expression of FBXL6 in GC tissues and adjacent normal tissues. Reverse transcription-quantitative polymerase chain reaction, immunofluorescence, and western blotting were used to detect the expression of FBXL6 in GC tissue and cell lines. Cell clone formation, 5-ethynyl-2'-deoxyuridine (EdU) assays, CCK-8, transwell migration assay, and wound healing assays were performed to evaluate the malignant biological behavior in GC cell lines after transfection with FBXL6-shRNA and the overexpression of FBXL6 plasmids. Furthermore, in vivo tumor assays were performed to prove whether FBXL6 promoted cell proliferation in vivo. RESULTS: FBXL6 expression was upregulated more in tumor tissues than in adjacent normal tissues and positively associated with clinicopathological characteristics. The outcomes of CCK-8, clone formation, and Edu assays demonstrated that FBXL6 knockdown inhibited cell proliferation, whereas upregulation of FBXL6 promoted proliferation in GC cells. Additionally, the transwell migration assay revealed that FBXL6 knockdown suppressed migration and invasion, whereas the overexpression of FBXL6 showed the opposite results. Through the subcutaneous tumor implantation assay, it was evident that the knockdown of FBXL6 inhibited GC graft tumor growth in vivo. Western blotting showed that the effects of FBXL6 on the expression of the proteins associated with the epithelial-mesenchymal transition-associated proteins in GC cells. CONCLUSION: Silencing of FBXL6 inactivated the EMT pathway to suppress GC malignancy in vitro. FBXL6 can potentially be used for the diagnosis and targeted therapy of patients with GC.

Sex differences in hippocampal ß-amyloid accumulation in the triple-transgenic mouse model of Alzheimer's disease and the potential role of local estrogens.

Introduction: Epidemiological studies show that women have a higher prevalence of Alzheimer's disease (AD) than men. Peripheral estrogen reduction during aging in women is proposed to play a key role in this sex-associated prevalence, however, the underlying mechanism remains elusive. We previously found that transcription factor early growth response-1 (EGR1) significantly regulates cholinergic function. EGR1 stimulates acetylcholinesterase (AChE) gene expression and is involved in AD pathogenesis. We aimed to investigate whether the triple-transgenic AD (3xTg-AD) mice harboring PS1 M146V , APP Swe , and Tau P301L show sex differences in ß-amyloid (Aß) and hyperphosphorylated tau (p-Tau), the two primary AD hallmarks, and how local 17ß-estradiol (E2) may regulate the expression of EGR1 and AChE. Methods: We first sacrificed male and female 3xTg-AD mice at 3-4, 7-8, and 11-12 months and measured the levels of Aß, p-Tau, EGR1, and AChE in the hippocampal complex. Second, we infected SH-SY5Y cells with lentivirus containing the amyloid precursor protein construct C99, cultured with or without E2 administration we measured the levels of extracellular Aß and intracellular EGR1 and AChE. Results: Female 3xTg-AD mice had higher levels of Aß compared to males, while no p-Tau was found in either group. In SH-SY5Y cells infected with lentivirus containing the amyloid precursor protein construct C99, we observed significantly increased extracellular Aß and decreased expression of intracellular EGR1 and AChE. By adding E2 to the culture medium, extracellular Aß(l-42) was significantly decreased while intracellular EGR1 and AChE expression were elevated. Discussion: This data shows that the 3xTg-AD mouse model can be useful for studying the human sex differences of AD, but only in regards to Ap. Furthermore, in vitro data shows local E2 may be protective for EGR1 and cholinergic functions in AD while suppressing soluble Aß(1-42) levels. Altogether, this study provides further in vivo and in vitro data supporting the human epidemiological data indicating a higher prevalence of AD in women is related to changes in brain estrogen levels.

Sexually dimorphic age-related molecular differences in the entorhinal cortex of cognitively intact elderly: Relation to early Alzheimer's changes.

INTRODUCTION: Women are more vulnerable to Alzheimer's disease (AD) than men. The entorhinal cortex (EC) is one of the earliest structures affected in AD. We identified in cognitively intact elderly different molecular changes in the EC in relation to age. METHODS: Changes in 12 characteristic molecules in relation to age were determined by quantitative immunohistochemistry or in situ hybridization in the EC. They were arbitrarily grouped into sex steroid-related molecules, markers of neuronal activity, neurotransmitter-related molecules, and cholinergic activity-related molecules. RESULTS: The changes in molecules indicated increasing local estrogenic and neuronal activity accompanied by a higher and faster hyperphosphorylated tau accumulation in women's EC in relation to age, versus a mainly stable local estrogenic/androgenic and neuronal activity in men's EC. DISCUSSION: EC employs a different neurobiological strategy in women and men to maintain cognitive function, which seems to be accompanied by an earlier start of AD in women. HIGHLIGHTS: Local estrogen system is activated with age only in women's entorhinal cortex (EC). EC neuronal activity increased with age only in elderly women with intact cognition. Men and women have different molecular strategies to retain cognition with aging. P-tau accumulation in the EC was higher and faster in cognitively intact elderly women.

Does Upward Social Comparison on SNS Inspire Adolescent Materialism? Focusing on the Role of Self-Esteem and Mindfulness.

The present study tested the mediating role of self-esteem and the moderating role of mindfulness in the association between upward social comparison on social network sites (SNSs) and adolescent materialism. A sample of 880 Chinese adolescents completed measures of upward social comparison on SNSs, materialism, self-esteem, mindfulness, and demographic information. Results showed that self-esteem mediated the link between upward social comparison on SNSs and adolescent materialism. That is, upward social comparison on SNSs was positively associated with adolescent materialism through the decreased self-esteem. Moreover, mindfulness acted as an important moderator in the mediation model. Both the direct association between upward social comparison on SNSs and materialism and the indirect association via self-esteem were moderated by mindfulness. These two associations were both weaker for adolescents with higher mindfulness than for those with lower mindfulness. These findings would advance our understanding of how and when upward social comparison on SNSs is associated with adolescent materialism. Limitations and implications of the present study are discussed.

Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke.

Although bone marrow mesenchymal stem cells (BMSCs) might have therapeutic potency in ischemic stroke, the benefits are limited. The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor (VEGF) on behavioral defects in a rat model of transient cerebral ischemia, which was induced by middle cerebral artery occlusion. VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke. We found that compared with the stroke-only group and the vehicle- and BMSCs-control groups, the VEGF-BMSCs treated animals displayed the largest benefits, as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke. Additionally, VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier, increased the regeneration of blood vessels in the region of ischemic penumbra, and reducedneuronal degeneration surrounding the infarct core. Further mechanistic studies showed that among all transplant groups, VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor. These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

Nonsyndromic supernumerary teeth in patients in National Taiwan University Children's hospital.

Background/purpose: A literature review reveals limited data for supernumerary teeth in Taiwan. This study aimed to analyze the characteristics of nonsyndromic supernumerary teeth in patients in the National Taiwan University Children's Hospital. Materials and methods: This retrospective study analyzed the nonsyndromic supernumerary teeth in 1280 patients (710 boys and 570 girls) based on examination of mainly panoramic radiographs and related radiographs. Chi-square test was used for trend analysis. Results: The incidence of nonsyndromic supernumerary teeth was 11.25% (179 supernumerary teeth in 144 of the 1280 patients). There was a male predominance (4.33: 1, P < 0.0001) for our 144 patients. Most supernumerary teeth were single (63.69%), conical-shaped (78.77%), and unerupted (77.09%). Supernumerary teeth also tended to be located in the premaxilla (93.85%), fully developed (51.40%), invertedly oriented (45.25%), sagittally located in a palatal/lingual position (67.60%), and adjacent to the root and root apex of permanent teeth (70.39%). The supernumerary teeth with a normal orientation (64.52%) had a high potential to erupt into the oral cavity, but the majority of the supernumerary teeth with a transverse orientation (97.22%) or an inverted orientation (100%) were unerupted. Conclusion: The nonsyndromic supernumerary teeth occur most commonly in male patients with a male to female ratio of 4.33: 1. The incidence of nonsyndromic supernumerary teeth in our 1280 patients is 11.25%, and the most frequent location of supernumerary teeth is the anterior maxillary region. More than three quarters of supernumerary teeth are conical-shaped or unerupted. Inverted supernumerary teeth are all embedded in the jawbones.

Self-Control, Parental Monitoring, and Adolescent Problematic Mobile Phone Use: Testing the Interactive Effect and Its Gender Differences.

Previous studies have revealed that self-control was one of the critical factors of adolescent problematic mobile phone use. Few studies, however, have explored the interaction of internal control force (i.e., self-control) and external control force such as parental monitoring. The present study tested the interactive effect of self-control and parental monitoring on adolescent problematic mobile phone use and its gender differences. A sample of 926 adolescents completed our anonymous self-report survey. Results showed that self-control and parental monitoring negatively predicted problematic mobile phone use, while gender positively predicted problematic mobile phone use. Self-control and parental monitoring had an interactive effect on problematic mobile phone use, with the effect of self-control on problematic mobile phone use being stronger for adolescents with low levels of parental monitoring than for those with high levels of parental monitoring. Self-control and gender had an interactive effect on problematic mobile phone use, with the effect of self-control on adolescent problematic mobile phone use being stronger in girls than in boys. Moreover, there were significant gender differences in the interaction of self-control and parental monitoring, in that the interactive effect of self-control and parental monitoring on problematic mobile phone use was more potent in girls than in boys. The findings reveal how the internal control force (i.e., self-control) and external control force (i.e., parental monitoring) work together in explaining adolescent problematic mobile phone use and uncover the potential gender differences in exploring adolescent problematic mobile phone use from the individual-environment perspective. Limitations and implications are discussed.

[Effects of moso bamboo (Phyllostachys edulis) expansion on soil microbial community in evergreen broad-leaved forest]. / æ¯›ç«¹æ‰©å¼ å¯¹å¸¸ç»¿é˜”å¶æž—åœŸå£¤å¾®ç”Ÿç‰©ç¾¤è½çš„å½±å“.

The special eco-physiological characteristics of moso bamboo (Phyllostachys edulis) facilitate their fast invasion in nature ecosystems. The widespread expansion of moso bamboo causes degradation of adjacent forest ecosystem and change of landscape, as well as soil properties and microbial community composition. However, how moso bamboo expansion affects soil microbial composition is far from fully understood. Herein, we selected four moso bamboo expansion transects with three forest types at the Anji Lingfeng temple forest farm, Zhejiang Province, including evergreen broadleaved forest (BLF), mixed P. edulis and broadleaved forest (MEF) and P. edulis forest (PEF). We examined the effects of moso bamboo expansion on soil properties and soil microbial phospholipid fatty acids (PLFAs). Our results showed that soil pH was higher in moso bamboo forest than in MEF and BLF by 0.37 and 0.32 unit. In contrast, soil organic carbon, ammonium, and nitrate contents significantly decreased. Biomass of soil microbial groups displayed a decreasing trend except arbuscular mycorrhizal fungi, and the microbial richness index (SR) and diversity index (H) decreased significantly. In summary, moso bamboo expansion affected soil nutrient and carbon inputs, which was an important factor affecting soil microbial community structure. Results of redundancy analysis showed that changes of soil organic carbon and ammonium content were the main factors driving soil microbial community.

Distinguishing Different Types of Mobile Phone Addiction: Development and Validation of the Mobile Phone Addiction Type Scale (MPATS) in Adolescents and Young Adults.

Researchers have developed various versions of scales to measure mobile phone addiction. Existing scales, however, focus primarily on the overall level of mobile phone addiction but do not distinguish the potential differences between different types of mobile phone addiction. There is a lack of established scales that can measure different types of mobile phone addiction. The present study aimed to uncover the specific types of mobile phone addiction and develop a Mobile Phone Addiction Type Scale (MPATS) for adolescents and young adults. Adolescents and young adults from two high schools and two universities in Central and South China participated in our study. A total of 108 mobile phone addicts (Mage = 17.60 years, SD = 3.568 years; 60.185% males) were interviewed to uncover the specific types of mobile phone addiction. Data from 876 adolescents and young adults (Mage = 16.750 years, SD = 3.159 years; 49.087% males) were tested for item discrimination and exploratory factor analysis. Data from 854 adolescents and young adults (Mage = 16.750 years, SD = 3.098 years; 50.820% males) were analyzed for construct validity, convergent validity, criterion-related validity, and internal consistency reliability. The 26-item Mobile Phone Addiction Type Scale (MPATS) was developed with four factors named mobile social networking addiction, mobile game addiction, mobile information acquisition addiction, and mobile short-form video addiction. The four-factor, 26-item MPATS revealed good construct validity, convergent validity, criterion-related validity, and internal consistency reliability. The new scale is suitable for measuring different types of mobile phone addiction in adolescents and young adults. Limitations and implications are discussed.

Development and validation of a GRGPI model for predicting the prognostic and treatment outcomes in head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is among the most lethal and most prevalent malignant tumors. Glycolysis affects tumor growth, invasion, chemotherapy resistance, and the tumor microenvironment. Therefore, we aimed at identifying a glycolysis-related prognostic model for HNSCC and to analyze its relationship with tumor immune cell infiltrations. Methods: The mRNA and clinical data were obtained from The Cancer Genome Atlas (TCGA), while glycolysis-related genes were obtained from the Molecular Signature Database (MSigDB). Bioinformatics analysis included Univariate cox and least absolute shrinkage and selection operator (LASSO) analyses to select optimal prognosis-related genes for constructing glycolysis-related gene prognostic index(GRGPI), as well as a nomogram for overall survival (OS) evaluation. GRGPI was validated using the Gene Expression Omnibus (GEO) database. A predictive nomogram was established based on the stepwise multivariate regression model. The immune status of GRGPI-defined subgroups was analyzed, and high and low immune groups were characterized. Prognostic effects of immune checkpoint inhibitor (ICI) treatment and chemotherapy were investigated by Tumor Immune Dysfunction and Exclusion (TIDE) scores and half inhibitory concentration (IC50) value. Reverse transcription-quantitative PCR (RT-qPCR) was utilized to validate the model by analyzing the mRNA expression levels of the prognostic glycolysis-related genes in HNSCC tissues and adjacent non-tumorous tissues. Results: Five glycolysis-related genes were used to construct GRGPI. The GRGPI and the nomogram model exhibited robust validity in prognostic prediction. Clinical correlation analysis revealed positive correlations between the risk score used to construct the GRGPI model and the clinical stage. Immune checkpoint analysis revealed that the risk model was associated with immune checkpoint-related biomarkers. Immune microenvironment and immune status analysis exhibited a strong correlation between risk score and infiltrating immune cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis showed typical immune pathways. Furthermore, the GRGPIdel showed excellent predictive performance in ICI treatment and drug sensitivity analysis. RT-qPCR showed that compared with adjacent non-tumorous tissues, the expressions of five genes were significantly up-regulated in HNSCC tissues. Conclusion: The model we constructed can not only be used as an important indicator for predicting the prognosis of patients but also had an important guiding role for clinical treatment.

Analysis of Glomerular IgG Subclasses Switch in Idiopathic Membranous Nephropathy Classified by Glomerular Phospholipase A2 Receptor Antigen and Serum Antibody.

BACKGROUND: The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively. METHODS: Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related (n = 132) and PLA2R-unrelated (n = 25) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN. RESULTS: We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass (P > 0.05). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup (P = 0.044, P = 0.013). PLA2R-related subgroup showed higher IgG4 intensity (2.1 ± 0.6 vs. 1.6 ± 0.7, P = 0.001) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, P = 0.015) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages (P > 0.05). CONCLUSIONS: Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.

Childhood trauma mediates repetitive transcranial magnetic stimulation efficacy in major depressive disorder.

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy.

Bidirectional planar-displacement waveguide tracker for high-concentration photovoltaics.

A bidirectional planar-displacement waveguide tracker was devised to replace the traditional two-axis tracking system for high-concentration photovoltaics, with improved module thickness, optical field uniformity, and current matching. The concentrating magnification reaches 725 times, and the sun tracking angle is more than 170°, which is equivalent to 11.3 tracking hours per day. The module thickness is only 6.16 cm. This design enabled us to place the module flat on the ground, in which swing was not required. This will greatly improve the mechanical strength and the lifetime of the module and solve the development dilemma faced by III-V multijunction solar cells.

Sex differences in the neuropathological hallmarks of Alzheimer's disease: focus on cognitively intact elderly individuals.

AIMS: Women are more vulnerable to Alzheimer's disease (AD) than men. We investigated (i) whether and at what age the AD hallmarks, that is, ß-amyloid (Aß) and hyperphosphorylated Tau (p-Tau) show sex differences; and (ii) whether such sex differences may occur in cognitively intact elderly individuals. METHODS: We first analysed the entire post-mortem brain collection of all non-demented 'controls' and AD donors from our Brain Bank (245 men and 403 women), for the presence of sex differences in AD hallmarks. Second, we quantitatively studied possible sex differences in Aß, Aß42 and p-Tau in the entorhinal cortex of well-matched female (n = 31) and male (n = 21) clinically cognitively intact elderly individuals. RESULTS: Women had significantly higher Braak stages for tangles and amyloid scores than men, after 80 years. In the cognitively intact elderly, women showed higher levels of p-Tau, but not Aß or Aß42, in the entorhinal cortex than men, and a significant interaction of sex with age was found only for p-Tau but not Aß or Aß42. CONCLUSIONS: Enhanced p-Tau in the entorhinal cortex may play a major role in the vulnerability to AD in women.