Detection of folate receptor-positive circulating tumor cells as a biomarker for diagnosis, prognostication, and therapeutic monitoring in breast cancer.

OBJECTIVES: This study is to explore the clinical significance of folate receptor-positive circulating tumor cells (FR+ CTC) in the early diagnosis and disease progress in patients with breast cancer. METHODS: Folate receptor-positive circulating tumor cells was enriched from peripheral blood of the patients with immunomagnetic separation method and quantitated by folate receptor on the CTC with the ligand-targeted PCR. RESULTS: The levels of FR+ CTC were significantly higher in breast cancer patients compared with healthy controls. Detective rate of FR+ CTC was decreased in 19 of 27 patients underwent the surgery in 2 weeks post-operation compared with pre-operation; statistical analysis showed the difference was significant. We also found that the combination of FR+ CTC, CEA, CA125, and CA153 can significantly improve the diagnostic efficiency for breast cancer. CONCLUSIONS: This study showed the detective rate of FR+ CTC is significantly increased in the patients with breast cancer, and the detective level is associated with disease progress.

Necessity for detection of SARS-CoV-2 RNA in multiple types of specimens for the discharge of the patients with COVID-19.

BACKGROUND: The SARS-CoV-2 RNA was detected positive again after discharged from hospital in some COVID-19 patients, with or without clinical symptoms such as fever or dry cough. METHODS: 1008 severe COVID-19 patients, with SARS-CoV-2 RNA positive detected with the mixed specimen of nasopharyngeal swab and oropharyngeal swab by real-time fluorescence quantitative PCR (RT-qPCR), were selected to monitor SARS-CoV-2 RNA with the 12 types of specimens by RT-qPCR during hospitalization. All of 20 discharged cases with COVID-19 were selected to detect SARS-CoV-2 RNA in isolation period with 7 types of specimens by RT-qPCR before releasing the isolation period. RESULTS: Of the enrolled 1008 severe patients, the nasopharyngeal swab specimens showed the highest positive rate of SARS-CoV-2 RNA (71.06%), followed by alveolar lavage fluid (66.67%), oropharyngeal swab (30.77%), sputum (28.53%), urine (16.30%), blood (12.5%), stool (12.21%), anal swab (11.22%) and corneal secretion (2.99%), and SARS-CoV-2 RNA couldn't be detected in other types of specimen in this study. Of the 20 discharged cases during the isolation period, the positive rate of SARS-CoV-2 RNA was 30% (6/20): 2 cases were positive in sputum at the eighth and ninth day after discharge, respectively, 1 case was positive in nasopharynx swab at the sixth day after discharge, 1 case was positive in anal swab at the eighth day after discharge, and 1 case was positive in 3 specimens (nasopharynx swab, oropharynx swab and sputum) simultaneously at the fourth day after discharge, and no positive SARS-CoV-2 RNA was detected in other specimens including stool, urine and blood at the discharged patients. CONCLUSIONS: SARS-CoV-2 RNA should be detected in multiple specimens, such as nasopharynx swab, oropharynx swab, sputum, and if necessary, stool and anal swab specimens should be performed simultaneously at discharge when the patients were considered for clinical cure and before releasing the isolation period.

A novel G6PD deleterious variant identified in three families with severe glucose-6-phosphate dehydrogenase deficiency.

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (D-G6PD) is an X-linked recessive disorder resulted from deleterious variants in the housekeeping gene Glucose-6-phosphate 1-dehydrogenase (G6PD), causing impaired response to oxidizing agents. Screening for new variations of the gene helps with early diagnosis of D-G6PD resulting in a reduction of disease related complications and ultimately increased life expectancy of the patients. METHODS: One thousand five hundred sixty-five infants with pathological jaundice were screened for G6PD variants by Sanger sequencing all of the 13 exons, and the junctions of exons and introns of the G6PD gene. RESULTS: We detected G6PD variants in 439 (28.1%) of the 1565 infants with pathological jaundice. In total, 9 types of G6PD variants were identified in our cohort; and a novel G6PD missense variant c.1118 T > C, p.Phe373Ser in exon 9 of the G6PD gene was detected in three families. Infants with this novel variant showed decreased activity of G6PD, severe anemia, and pathological jaundice, consistent with Class I G6PD deleterious variants. Analysis of the resulting protein's structure revealed this novel variant affects G6PD protein stability, which could be responsible for the pathogenesis of D-G6PD in these patients. CONCLUSIONS: High rates of G6PD variants were detected in infants with pathological jaundice, and a novel Class I G6PD deleterious variants was identified in our cohort. Our data reveal that variant analysis is helpful for the diagnosis of D-G6PD in patients, and also for the expansion of the spectrum of known G6PD variants used for carrier detection and prenatal diagnosis.

Overexpression of MALAT1 contributes to cervical cancer progression by acting as a sponge of miR-429.

Cervical cancer remains a malignant type of tumor and is the fourth leading cause of cancer-related death among females. MALAT1 has been identified as a tumor oncogene in various cancers. Our present study aimed to explore the biological role of MALAT1 in cervical cancer. We observed that MALAT1 was significantly upregulated in human cervical cancer cell lines compared with the ectocervical epithelial cells. MALAT1 was repressed by transfection with LV-shMALAT1, whereas increased by LV-MALAT1 in HeLa and Caski cells. Silencing of MALAT1 obviously reduced cervical cell viability, induced cell apoptosis, and repressed cell invasion capacity. Conversely, overexpression of MALAT1 exhibited an opposite phenomenon. Furthermore, miR-429 was predicted as a direct target of MALAT1, and it was dramatically decreased in cervical cancer cells. It has been shown that miR-429 plays a crucial role in cervical cancer progression. In our current study, the targeting correlation between MALAT1 and miR-429 was confirmed by luciferase reporter assays and RIP experiments. Finally, in vivo animal models were established, and we indicated that MALAT1 inhibited cervical cancer progression via targeting miR-429. These findings revealed that MALAT1 can sponge miR-429 and regulate cervical cancer pathogenesis in vivo and in vitro. In conclusion, we indicated that the MALAT1/miR-429 axis was involved in cervical cancer development.

Identification of CD28 and PTEN as novel prognostic markers for cervical cancer.

Cervical cancer (CC) is the most common malignant tumor with poor clinical outcome among women. Identification of novel biomarkers could be beneficial for the clinical diagnosis and treatment of CC. This study aimed to identify prognostic biomarkers for the prediction of prognostic status of CC patients, and explore the effect of the corresponding methylated genes in the occurrence and development of CC. The methylation microarray data of CC was extracted from The Cancer Genome Atlas (TCGA) dataset. The methylation genes associated with the prognostic status were identified based on the information of the relapse-free survival (RFS) of the CC patients. The prognostic gene pairs were further identified. Then, the prognostic signature was identified by the forward search algorithm based on the C-index method. The results were validated by independent dataset. Finally, the functional analysis was performed on the methylation genes. A total of 276 methylation genes and 2508 gene pairs associated with the prognostic status of the CC were identified. A signature composed of eight methylation gene pairs was obtained to predict the prognostic status of cervical patients. A series of genes that played an important role in the occurrence and development of CC were obtained by the functional enrichment analysis. To summary, a prognostic signature consisting of eight methylation gene pairs was obtained. Of note, the CD28 and PTEN gene pair were found to play important roles in the occurrence and development of CC.

LINC00657 expedites neuropathic pain development by modulating miR-136/ZEB1 axis in a rat model.

Long non-coding RNAs (lncRNAs) are involved in the progression of several diseases. The interactions among lncRNAs, microRNA (miRNAs) or their targeting genes are reported to play crucial roles in the development of diseases. LINC00657 is observed to be upregulated in several cancers. However, the biological role of LINC00657 in neuropathic pain progress is unclear. Hence, in our study, we aimed to investigate the function of LINC00657 in neuropathic pain development. A chronic constriction injury (CCI) rat model was established, and we found that LINC00657 was greatly increased in CCI rats associated with a decrease of miR-136. Inhibition of LINC00657 suppressed neuropathic pain via alleviating mechanical and thermal hyperalgesia. In addition, miR-136 overexpression can also inhibit the neuropathic pain development. MiR-136 was predicted to serve as a miRNA target of LINC00657, and dual-luciferase reporter assay confirmed the correlation between LINC00657 and miR-136. Moreover, we observed that the decrease of LINC00657 was able to inhibit the neuroinflammation of CCI rats by targeting expression of cyclooxygenase-2, tumor necrosis factor-α and interleukin-1ß while miR-136 inhibitors reversed this phenomenon. Next, by using bioinformatics analysis, ZEB1 was predicted as a direct target of miR-136, and miR-136 could negatively modulate ZEB1 expression. Besides these, ZEB1 was remarkably increased in the CCI rats. Knockdown of ZEB1 can inhibit neuropathic pain development, while miR-136 inhibitors can reverse it. In conclusion, it was implied that LINC00657 can induce the neuropathic pain development via regulating miR-136/ZEB1 axis.

Planctomonas deserti gen. nov., sp. nov., a new member of the family Microbacteriaceae isolated from soil of the Taklamakan desert.

A Gram-staining-positive, aerobic, irregular coccoid- to ovoid-shaped, non-spore-forming and motile bacterium, designated strain 13S1-3T, was isolated from a soil sample from the rhizosphere of Tamarix collected in the Taklamakan desert in Xinjiang Uygur Autonomous Region, PR China. The strain was examined by a polyphasic approach to clarify its taxonomic position. Strain 13S1-3T grew optimally at 28-30 °C, pH 7.0 and with 0-1 % (w/v) NaCl. The cell-wall peptidoglycan was of the B2γ type and contained d-alanine, d-glutamic acid, glycine, d-2,4-diaminobutyric acid and l-2,4-diaminobutyric acid. Ribose, xylose, glucose and galactose were detected as cell-wall sugars. The acyl type of the muramic acid was acetyl. The predominant menaquinones were MK-12, MK-11, MK-13 and MK-10. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and one unidentified phospholipid. The major whole-cell fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The DNA G+C content was 70.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that 13S1-3T represented a member of the family Microbacteriaceae and showed the highest level of 16S rRNA gene sequence similarity with Frondihabitans australicus E1HC-02T (97.11 %). Phylogenetic trees revealed that 13S1-3T formed a distinct lineage with respect to closely related genera within the family Microbacteriaceae. On the basis of the results of phylogenetic, phenotypic and chemotaxonomic analyses, 13S1-3T is distinguishable from phylogenetically related genera in the family Microbacteriaceae, and represents a novel species of a new genus, for which the name Planctomonas deserti gen. nov., sp. nov. is proposed. The type strain is 13S1-3T (=KCTC 49115T=CGMCC 1.16554T).

Detection of viruses and atypical bacteria associated with acute respiratory infection of children in Hubei, China.

BACKGROUND AND OBJECTIVE: Acute respiratory infection is the major cause of disease and death in children, particularly in developing countries. However, the spectrum of pathogenic viruses and atypical bacteria that exist in many of these countries remains incompletely characterized. The aim of this study was to examine the spectrum of pathogenic viruses and atypical bacteria associated with acute respiratory infection in children under the age of 16. METHODS: A total of 10 435 serum sera specimens were collected from hospitalized children presenting with acute respiratory infection symptoms. Indirect immunofluorescence assays were performed to detect immunoglobulin M antibodies against nine common pathogens: mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila, coxiella burnetii and chamydophila pneumonia. RESULTS: Of the 10 435 specimens examined, 7046 tested positive for at least one pathogen. Among all of the tested pathogens, mycoplasma pneumonia had the highest detection rate (56.9%). Influenza virus A and influenza virus B epidemics occurred during both winter and summer. The detection rate of respiratory syncytial virus and adenovirus was higher in spring. Cases of mixed infection were more complex: 4136 specimens (39.6%) tested positive for ≥2 pathogens. There were statistically significant difference in detection rates of mycoplasma pneumonia, influenza virus B, respiratory syncytial virus, parainfluenza virus, adenovirus, influenza virus A, legionella pneumophila and chamydophila pneumonia among different age groups (P < 0.05). CONCLUSIONS: The most common pathogens causing acute respiratory infection among children in Hubei of China were mycoplasma pneumonia, influenza virus B and respiratory syncytial virus. The detection rates for each pathogen displayed specific seasonal and age group variations.

A novel universal multiplex PCR improves detection of AZFc Y-chromosome microdeletions.

PURPOSE: To determine the frequencies and the characteristics of Y chromosome microdeletions (pl) in infertile men from central China to perform appropriate therapeutic choices by updated multiplex-PCR. METHODS: In this study, we established a novel universal primer-multiplex-PCR (U-M-PCR) method to overcome the disadvantages of traditional multiplex PCR (M-PCR). We chose 15 sequence-tagged sites (STS) for detection of Y chromosome microdeletions. 540 infertile male patients and 100 healthy male controls were selected in the study. RESULTS: Of the 540 male infertility patients, 48 Y-chromosome microdeletions were detected, with a total deletion rate of 8.9 %. Of these deletions, the rate of AZFa deletions (sY84) was 0.5 % (3/540), the rate of AZFb deletions (sY143) was 0.7 % (4/540) and the rate of AZFc deletions (sY242, sY254 and sY255) was 7.6 % (41/540). Compared with AZF deletion rates by M-PCR, we found U-M-PCR could detect AZFc deletion more specifically (1.0 % & 7.6 %). No Y-chromosome microdeletions were detected in the 100 males with normal semen (the control group). CONCLUSIONS: U-M-PCR method was more specific to detect AZFc microdeletions. It is necessary to use the U-M-PCR method to offer genetic screening and counseling to infertile men prior to intracytoplasmic sperm injection (ICSI) or in-vitro fertilization (IVF).

Labeled-free quantitative proteomic analysis of cervical squamous cell carcinoma identifies potential protein biomarkers.

Background: Cervical cancer remains a prevalent cancer among women, and reliance on surgical and radio-chemical therapies can irreversibly affect patients' life span and quality of life. Thus, early diagnosis and further exploration into the pathogenesis of cervical cancer are crucial. Mass spectrometry technology is widely applied in clinical practice and can be used to further investigate the protein alterations during the onset of cervical cancer. Methods: Employing labeled-free quantitative proteomics technology and bioinformatics tools, we analyzed and compared the differential protein expression profiles between normal cervical squamous cell tissues and cervical squamous cell cancer tissues. GEPIA is an online website for analyzing the RNA sequencing expression data of tumor and normal tissue data from the TCGA and the GTEx databases. This approach aided in identifying qualitative and quantitative changes in key proteins related to the progression of cervical cancer. Results: Compared to normal samples, a total of 562 differentially expressed proteins were identified in cervical cancer samples, including 340 up-regulated and 222 down-regulated proteins. Gene ontology functional annotation, and KEGG pathway, and enrichment analysis revealed that the differentially expressed proteins mainly participated in metabolic pathways, spliceosomes, regulation of the actin cytoskeleton, and focal adhesion signaling pathways. Specifically, desmoplakin (DSP), protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L) and ANXA8 may be involved in cervical tumorigenesis by inhibiting apoptotic signal transmission. Moreover, we used GEPIA database to validate the expression of DSP, PPP1R13L and ANXA8 in human cancers and normal cervix. Conclusion: In this study, we identified 562 differentially expressed proteins, and there were three proteins expressed higher in the cervical cancer tissues. The functions and signaling pathways of these differentially expressed proteins lay a theoretical foundation for elucidating the molecular mechanisms of cervical cancer.

IL-4-induced M2 macrophages inhibit fibrosis of endometrial stromal cells.

BACKGROUND: Intrauterine adhesions (IUA) refers to endometrial fibrosis caused by irreversible damage of the endometrial basal layer. As the key regulators in tissue repair, regeneration, and fibrosis, macrophages play an essential role in endometrial regeneration and repair during the normal menstrual cycle. However, the mechanism of macrophages involved in IUA remains unclear. METHODS: In the late stages of proliferation, the endometrium was collected to make paraffin sections. HE and Masson staining were used to observing endometrial morphology and endometrial fibrosis. Immunohistochemistry and Western blotting were used to detect the expression level of fibrosis indexes COL1A1 and α-SMA. The macrophage infiltration was evaluated by immunohistochemistry for the expression levels of CD 206 and CD163. Next, we cultured the primary human endometrial stromal cells (HESCs), and then an IUA cell model was established with 10 ng/ml TGF-ß1 for 72 h. THP 1 cells were differentiated by 100 ng/ml PMA into macrophages for 48 h, then macrophages were polarized to M2 macrophages by 20 ng/ml IL-4 for 24 h. The culture supernatants (M(IL-4) -S) of M2 macrophages were applied to the IUA cell model. The expression of fibrosis markers was then assessed using immunofluorescence and Western blotting. RESULTS: The results show that Patients with IUA have fewer endometrial glands and significantly increased fibrosis levels. Moreover, the infiltration of CD206-positive (M2) macrophages was significantly reduced in IUA patients, and negatively correlated with the expression of endometrial fibrosis indexes α-SMA and COL1A1. In addition, the primary HESCs treated with 10 ng/ml TGF-ß1 for 72 h were found to have significantly increased levels of fibrosis indexes. Furthermore, supernatants from IL4-induced M2 macrophages inhibit the TGF-ß1-induced fibrosis of HESCs. CONCLUSIONS: M2 macrophages may negatively regulate the expression of COL1A1 and α-SMA, inhibiting the TGF-ß1-induced fibrosis of HESCs. Our study suggests that targeting macrophage phenotypes and promoting the polarization of macrophages to M2 may become a novel strategy for the clinical treatment of IUA.

Meta-analysis of the association of the rs2234693 and rs9340799 polymorphisms of estrogen receptor alpha gene with coronary heart disease risk in Chinese Han population.

OBJECTIVE: The association between a common variant of the ESR1 gene rs2234693 and rs9340799 polymorphisms with coronary heart disease (CHD) have been reported, but the available data on this relationship are inconsistent. A meta-analysis was performed to quantitative analysis the association of ESR1 gene polymorphisms and CHD risk using previous case-control studies in Chinese Han population. METHODS: Several electronic databases were searched for relevant articles up to August 2012. After data collection, a meta-analysis was performed to assess heterogeneity, combine results and evaluate variations. Different effect models were used according to the difference in heterogeneity. Sensitivity analysis was assessed by omitting one study at a time. Publication bias was examined using Begg's funnel plot and Egger's linear regression test. RESULTS: Ten studies covering 3400 subjects on rs2234693 and rs9340799 polymorphisms in the ESR1 gene with CHD risk was included in this meta-analysis. For rs2234693 polymorphism, ten studies were combined to the meta-analysis. A significantly increased CHD risk was found in a dominant model (OR=1.35, 955 CI=1.01-1.81, P=0.05), recessive model (OR=1.40, 95% CI=1.15-1.69, P=0.0007), and additive model (OR=1.67, 95% CI=1.19-2.34, P=0.003). Subgroup for male but not for female showed that the CC genotype could increase the risk of CHD compared with TT and TC genotype in Chinese Han population. Concerning rs9340799 polymorphism, eight studies were combined to the meta-analysis. And no evidence of significant association with CHD risk was found in all genetic models. CONCLUSION: Our meta-analysis of 10 studies involving Chinese Han population suggests that the CC genotype of the ESR1 rs2234693 polymorphism is significantly associated with an increased risk of CHD in males only. There was no evidence however, of a significant association between the ESR1 rs9340799 polymorphism and CHD risk.

Tumor-suppressive effects of 1, 25-dihydroxyvitamin D3 in gastric cancer cells.

BACKGROUNDS/AIMS: It has been previously demonstrated that vitamin D acts as a prognostic indicator of gastric cancer and may be correlated with the incidence risk of gastric cancer. However, the effect of 1,25-dihydroxyvitamin D3 on the apoptosis of human gastric cancer cells is unclear. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 induced the cellular apoptosis of BGC-823 gastric cancer cells and to determine the potential mechanism of action. METHODOLOGY: We demonstrate that 1,25-dihydroxyvitamin D3 induced the apoptosis of gastric cancer cells via the processing of PARP and cleavage of caspase 3. Additionally, an increase in BAX expression and a decrease in ERK1/2 and AKT phosphorylation were associated with 1,25-dihydroxyvitamin D3-induced apoptosis. The mRNA expression levels of VDR, CYP24A1, and p21 were increased significantly following 1,25-dihydroxyvitamin D3 treatment. CONCLUSIONS: These findings suggest that 1,25-dihydroxyvitamin D3 exerts tumor-suppressive effects on BGC-823 human gastric cancer cells.

Relationship between Internet Use and Negative Affect.

While positive emotions like happiness and life satisfaction have received great attention, how to eliminate negative affect is largely neglected. This study contributes to the literature by examining the relationship between Internet use and people's negative affect. Unlike previous studies that consider only one indicator, we capture negative affect from different dimensions by considering loneliness, sadness, and life hardship. We employ an endogenous ordered probit model to address the selection bias of Internet use and analyze the 20,107 individual-level samples sourced from the 2020 China Family Panel Studies survey. The results show that Internet use significantly reduces people's loneliness, sadness, and life hardship. We also find that studying online and watching short videos would increase people's loneliness feeling and shopping online deepens people's life hardship. In contrast, using WeChat significantly reduces sadness and life hardship. Our findings confirm that guiding people to use the Internet appropriately is necessary to reduce negative affect and improve the quality of their life.

Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects.

Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor-specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure-targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle-targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug-related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle-targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle-targeting functional materials in precision oncology. The review will serve as an excellent cutting-edge guide for researchers in the field of subcellular organelle-targeted cancer therapy.

An Innovative Teaching Approach for Diabetes Mellitus in Laboratory Medicine Uses the Clinical Laboratory Diagnostic Pathway.

Objectives: The routine teaching mode of diabetes mellitus (DM) is divided into various sub-majors of medical laboratory, which is not conducive to clinical laboratory physicians quickly mastering relevant knowledge. A novel DM laboratory testing pathway is established to improve teaching efficiency and enhance the effects of talent cultivation in laboratory medicine. Methods: The guidelines and expert consensuses of DM were gathered from professional websites and databases. The clinical laboratory diagnostic pathway was formulated, and the questionnaire and mutual evaluation were used to evaluate the teaching effectiveness of 8-year undergraduate students enrolled in 2018 and enrolled in 2019, respectively. Results: Clinical laboratory physicians developed and approved the DM clinical laboratory diagnostic pathway, which included the entire process of DM diagnosis and differential diagnosis, drug selection, treatment impact monitoring, prognosis evaluation, etc. The results of the questionnaires showed that, in comparison to the teaching mode used with the students enrolled in 2018 and enrolled in 2019, the percentages of more improvement and significant improvement were significantly increased (P < 0.01) and the percentages of no improvement and slight improvement were significantly decreased (P < 0.01). Following the instruction of the DM clinical laboratory diagnostic route, the results were greatly improved, including points emphasized and the accuracy of responding to questions, among other things, according to the teachers' and students' mutual evaluation (P < 0.05). Conclusions: To enhance the teaching quality in laboratory medicine, it is required to build the disease clinical laboratory diagnostic pathway for a novel teaching method. This may boost teachers' and students' confidence and broaden their knowledge.

Upregulation of astrocytes protein phosphatase-2A stimulates astrocytes migration via inhibiting p38 MAPK in tg2576 mice.

One of the earliest neuropathological changes in Alzheimer disease (AD) is the accumulation of astrocytes at sites of ß-amyloid (Aß) deposits, but the cause of this cellular response is unclear. As the activity of protein phosphatase 2A (PP2A) is significantly decreased in the AD brains, we studied the role of PP2A in astrocytes migration. We observed unexpectedly that PP2A activity associated with glial fibrillary acidic protein, an astrocyte marker, was significantly upregulated in tg2576 mice, demonstrated by an increased enzyme activity, a decreased demethylation at leucine-309 (DM-PP2Ac), and a decreased phosphorylation at tyrosine-307 of PP2A (pY307-PP2Ac). Further studies by using in vitro wound-healing model and transwell assay demonstrated that upregulation of PP2A pharmacologically and genetically could stimulate astrocytes migration. Activation of PP2A promotes actin organization and inhibits p38 mitogen-activated protein kinases (p38 MAPK), while simultaneous activation of p38 MAPK partially abolishes the PP2A-induced astrocytes migration. Our data suggest that activation of astrocytes PP2A in tg2567 mice may stimulate the migration of astrocytes to the amyloid plaques by p38 MAPK inhibition, implying that PP2A deficits observed in AD may cause Aß accumulation via hindering the astrocytes migration.

Estradiol/Testosterone imbalance: impact on coronary heart disease risk factors in postmenopausal women.

OBJECTIVE: Several groups have reported the important role of the estradiol/testosterone (E2/T) ratio in benign prostatic hyperplasia and cerebral vessels. However, there has been no study on the role of the E2/T ratio in women with coronary heart disease (CHD). This study aimed to evaluate the association among the ratio of sex hormones and known risk factors of atherosclerosis in postmenopausal women with CHD. METHODS: 114 controls and 124 postmenopausal women with CHD were selected for this study. Serum levels of estradiol, testosterone, aromatase, sex hormone-binding globulin (SHBG), lipid-lipoprotein profile and high-sensitivity C-reactive protein were determined. RESULTS: Compared with the control, the E2/T ratio decreased from 5.35 ± 2.78 to 3.88 ± 2.51 (p < 0.0001). Multiple linear regression analysis showed that the E2/T ratio was negatively associated with total cholesterol, low-density lipoprotein cholesterol (LDL-c) and the atherogenic index of plasma, but positively associated with high-density lipoprotein cholesterol (HDL-c) and HDL-c/LDL-c (for all, p < 0.0001). We found that there was a negative correlation between the E2/T ratio and aromatase (r = -0.192, p = 0.032) and a positive correlation between aromatase and SHBG (r = 0.938). CONCLUSION: The balance of the serum E2/T ratio was broken in the women with CHD, and an imbalanced E2/T ratio showed a strong association with cardiovascular risk factors in postmenopausal women with CHD.

Does online food shopping boost dietary diversity? Application of an endogenous switching model with a count outcome variable.

Increasingly, rural households in developing countries are shopping for food online, and the COVID-19 pandemic has accelerated this trend. In parallel, dietary guidelines worldwide recommend eating a balanced and healthy diet. With this in mind, this study explores whether online food shopping boosts dietary diversity-defined as the number of distinct food groups consumed-among rural households in China. Because people choose to shop for food online, it is important to account for the self-selection bias inherent in online food shopping. Accordingly, we estimate the treatment effects of online food shopping on dietary diversity using the endogenous switching model with a count outcome variable. The results indicate that online food shopping increases dietary diversity by 7.34%. We also find that education, asset ownership, and knowing the government's dietary guidelines are the main factors driving rural households' decisions to shop for food online.

Associations of dietary Provitamin A carotenoid intake with depressive symptoms in midlife women: Results from the study of Women's Health Across the Nation.

BACKGROUND: To study the association of Provitamin A (pro-A) carotenoid intake from diet with depressive symptoms in midlife women. METHODS: Data for this cross-sectional study were retrieved from baseline assessment of the Study of Women's Health Across the Nation (SWAN). Logistic regression and restricted cubic spline models were performed to examine the association pro-A carotenoid intake with depressive symptoms. RESULTS: A total of 3054 midlife women aged 42-52 years were included in the present study. In overall midlife women, pro-A carotenoid intake was inversely associated with depressive symptoms (CES-D score ≥16). In premenopausal women, pro-A carotenoid intake was inversely associated with depressive symptoms after adjustment for age, race/ethnicity, total family income, education, physical activity, BMI, use of antidepressant, dietary total caloric, protein, carbohydrate, fat, vitamin C, vitamin E and pro-A carotenes in model 1. In fully adjusted model, after additional adjustment for day of cycle, FSH and SHBG, this association remained statistically significant. The fully adjusted odds ratios (ORs) with 95 % CI of depressive symptoms were 0.685 (0.450-1.043) in quartile 4 compared with quartile 1 for pro-A carotenoid intake. However, in early perimenopausal women, no statistically significant difference was observed between pro-A carotenoid intake and depressive symptoms after adjustment for confounders. LIMITATIONS: This was a cross-sectional study, limiting causal inferences. Assessment of CES-D was based on a self-report scale. CONCLUSION: Pro-A carotenoid intake may be inversely associated with depression symptoms in premenopausal women, but not in early perimenopausal women.