Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

Investigating the spontaneous brain activities of patients with subjective cognitive decline and mild cognitive impairment: an amplitude of low-frequency fluctuation functional magnetic resonance imaging study.

Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are neurodegenerative processing stages of Alzheimer's disease (AD). Cognitive decline is thought to manifest in intrinsic brain activity changes, but research results yielded conflicting and few studies have explored the roles of brain regions in cognitive decline, and sensitivity of the cognitive field to changes in the altered intrinsic brain activity. Methods: In this cross-sectional study, 158 elderly participants were recruited from the memory clinic of the First Affiliated Hospital of Nanjing Medical University from July 2019 to May 2021, and grouped into SCD (n=73), MCI (n=46), and normal controls (NC) (n=39). The amplitude of low-frequency fluctuation (ALFF) was calculated and evaluated among the groups. Then canonical correlation analysis (CCA) was conducted to investigate the associations between imaging outcomes and cognitive behaviors. Results: Neuropsychological tests in different cognitive dimensions and ALFF values of the prefrontal, parietal, and temporal gyrus, were significantly different (P<0.05) among the three groups, with no appreciable decline in daily activity. The changes in intrinsic activities were closely related to the decline in cognitive function (R=0.73, P=0.002). ALFF values in the left middle occipital gyrus, right middle frontal gyrus, left superior frontal gyrus, left angular gyrus, and superior temporal gyrus played significant roles in the analysis, while the Montreal Cognitive Assessment (MoCA) and Auditory-Verbal Learning Test scores were found to be more sensitive to changes in ALFF values. Conclusions: Spontaneous brain activity is a stable imaging biomarker of cognitive impairment. ALFF changes of the prefrontal, occipital, left angular, and temporal gyrus were sensitive to identifying cognitive decline, and the scores of the Auditory-Verbal Learning Test and MoCA could predict the abnormal intrinsic activities.

Urinary nicotine metabolites are associated with cognitive impairment among the elderly in southern China.

INTRODUCTION: This study comprehensively assessed the association between eight metabolites of urinary nicotine and cognitive impairment. METHODS: This cross-sectional study was based on the data of Shenzhen Aging Related Disorder Cohort (SADC), including 51 elderly community data variables such as demographic characteristics, neuropsychological assessment and environmental factors, from July 2017 to November 2018. Participant's cognitive function was assessed by Mini-Mental State Examination (MMSE) scale and urinary nicotine metabolite [including cotinine N-ß-D-glucuronide (CotGluc), rac 4-hydroxy-4-(3-pyridyl) butanoic acid dicyclohexylamine salt (HyPyBut), trans-3'-hydroxy cotinine O-ß-D-glucuronide (OHCotGluc), and cotinine (Cot), etc.] concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Generalized linear models and restricted cubic spline models were used to explore the relationships between the urinary levels of nicotine metabolite and cognitive function. RESULTS: A total of 296 individuals aged >60 years were included. Individuals in the third quartile of CotGluc had a 0.786 point (95% CI: -1.244 - -0.329) decrease or in the highest quartile of OHCotGluc had a 0.804 point (95% CI: -1.330 - -0.278) decreased in attention and calculation compared to those in the lowest quartile (all p for trend <0.05). Compared with those in the lowest quartile, individuals in the highest quartile of CotGluc, HyPyBut, OHCotGluc and Cot, respectively, corresponded to a 1.043 point (95% CI: -2.269-0.182), 1.101 points (95% CI: -2.391-0.188), 2.318 points (95% CI: -3.615 - -1.020), and 1.460 points (95% CI: -2.726 - -0.194) decreased in MMSE total score (all p for trend <0.05). A non-linear dose-response relationship between urinary levels of CotGluc, HyPyBut, OHCotGluc or Cot and cognitive function (all overall p<0.05, non-linear p<0.05). Subgroup analysis showed that urinary levels of CotGluc, OHCotGluc or Cot were significantly negatively associated with cognitive function (all p for trend <0.05) among females and non-smokers. CONCLUSIONS: The findings highlight the public health implications of environmental tobacco smoke exposure, and effective interventions need to be performed for vulnerable populations.

Managing Cancer and Living Meaningfully (CALM) alleviates chemotherapy related cognitive impairment (CRCI) in breast cancer survivors: A pilot study based on resting-state fMRI.

BACKGROUND: Chemotherapy related cognitive impairment (CRCI) is a type of memory and cognitive impairment induced by chemotherapy and has become a growing clinical problem. Breast cancer survivors (BCs) refer to patients from the moment of breast cancer diagnosis to the end of their lives. Managing Cancer and Living Meaningfully (CALM) is a convenient and easy-to-apply psychological intervention that has been proven to improve quality of life and alleviate CRCI in BCs. However, the underlying neurobiological mechanisms remain unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) has become an effective method for understanding the neurobiological mechanisms of brain networks in CRCI. The fractional amplitude of low-frequency fluctuations (fALFF) and ALFF have often been used in analyzing the power and intensity of spontaneous regional resting state neural activity. METHODS: The recruited BCs were randomly divided into the CALM group and the care as usual (CAU) group. All BCs were evaluated by the Functional Assessment of Cancer Therapy Cognitive Function (FACT-Cog) before and after CALM or CAU. The rs-fMRI imaging was acquired before and after CALM intervention in CALM group BCs. The BCs were defined as before CALM intervention (BCI) group and after CALM intervention (ACI) group. RESULTS: There were 32 BCs in CALM group and 35 BCs in CAU group completed the overall study. There were significant differences between the BCI group and the ACI group in the FACT-Cog-PCI scores. Compared with the BCI group, the ACI group showed lower fALFF signal in the left medial frontal gyrus and right sub-gyral and higher fALFF in the left occipital_sup and middle occipital gyrus. There was a significant positive correlation between hippocampal ALFF value and FACT-Cog-PCI scores. CONCLUSIONS: CALM intervention may have an effective function in alleviating CRCI of BCs. The altered local synchronization and regional brain activity may be correlated with the improved cognitive function of BCs who received the CALM intervention. The ALFF value of hippocampus seems to be an important factor in reflect cognitive function in BCs with CRCI and the neural network mechanism of CALM intervention deserves further exploration to promote its application.

Integrating Network Pharmacology and Experimental Validation Deciphers the Mechanism of Guizhi Fuling Wan against Adenomyosis.

AIM: This study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification. METHODS: The related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis. RESULTS: A total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells' estrogen resistance via GPER/EGFR signaling pathway. CONCLUSION: The endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.

NANOGP8 expression regulates gastric cancer cell progression by transactivating DBC1 in gastric cancer MKN-45 cells.

NANOGP8 is one of the NANOG pseudogenes and is expressed together with NANOG in multiple tumor tissues and cell lines. The biological functions of NANOGP8 in progression of gastric cancer are unclear. In the present study, the role of NANOGP8 was investigated in gastric cancer cells. The gathered data demonstrated that NANOG expression in both mRNA and protein was elevated in gastric cancer cell lines relative to a normal gastric epithelial cell line. Downregulation of NANOGP8 inhibited cell proliferation and increased apoptosis in human gastric carcinoma cell lines. Furthermore, silencing of NANOGP8 suppressed tumor growth in vivo. Interestingly, it was identified that deleted in breast cancer 1 (DBC1) expression was also markedly downregulated following NANOGP8 knockdown. DNA microarray and dual-luciferase assays further indicated that NANOGP8 may bind to the DBC1 promoter region and regulate DBC1 expression. Therefore, the gathered data provided evidence that NANOGP8 contributes to progression of gastric cancer via DBC1 and may have potential translational significance.

Efficacy and safety of combined high-dose interferon and red light therapy for the treatment of human papillomavirus and associated vaginitis and cervicitis: A prospective and randomized clinical study.

BACKGROUND: We evaluated the efficacy and safety of combined high-dose interferon (IFN) and red light therapy for the treatment of subclinical and latent human papillomavirus (HPV) infections. METHODS: Ninety women diagnosed with subclinical or latent HPV infection were randomized to receive topical application of low-dose recombinant IFNα-2b (1 million IU), high-dose IFNα-2b (9 million IU), or a combination of high-dose IFNα-2b and red light therapy on the cervix and vagina. All patients received treatment once daily for 4 weeks. HPV titer was measured immediately and 4, 8, and 12 weeks after treatment to determine the rates of viral clearance and infection cure. Treatment of HPV-associated vaginitis and cervicitis was also evaluated. RESULTS: Results showed that immediately and 4, 8, and 12 weeks after treatment, the HPV clearance rates and infection cure rates were higher in the high-dose IFN and combination groups compared to the low-dose IFN group. High-dose IFN and combination therapies were significantly effective against both low-risk and high-risk HPV infections. Although the cure rates for vaginitis and cervicitis were significantly higher in the high- compared to the low-dose IFN group, rates were even higher in the combination group compared to the high-dose IFN group. Mild adverse effects were reported by a very small subset of patients (3/30) in the combination group. CONCLUSIONS: This study suggests that combination of high-dose IFN and red light therapy is safe and effective against subclinical and latent HPV infections.

The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1.

BACKGROUND/AIMS: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in gastric cancer remain unclear. METHODS: Immunohistochemistry and qRT-PCR analyses were used to detect the expression levels of UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, cell proliferation, apoptosis, migration and invasion. Additionally, sodium bisulfate sequencing was used to test the promoter hypermethylation on UPF1 in gastric tumor tissues. Finally, RNA immunoprecipitation and luciferase reporter analyses demonstrated that UPF1 directly bound with MALAT1. RESULTS: The expression of UPF1 was significantly downregulated in gastric cancer and negatively correlated with MALAT1 expression. Patients with lower expression of UPF1 had poorer prognosis than those with higher expression. Overexpression of UPF1 inhibited cell proliferation, cell cycle progression, cell migration and invasion, and promoted cell apoptosis in gastric cancer cells. Moreover, the UPF1-mediated inhibition of gastric cancer progression was reversed by overexpression of MALAT1. A profound downregulation of UPF1 in gastric tumor tissues was due to promoter hypermethylation. Overexpression of UPF1 increased nonsense-mediated mRNA decay (NMD) efficiency and thus led to downregulation of MALAT1. CONCLUSION: Our results demonstrate that UPF1 is a potential modulator of MALAT1 and that UPF1/MALAT1 pathway could be a therapeutic target for gastric cancer.

Effects of home and education environments on children's motor performance in China.

AIM: The aim of this study was to examine the effects of home and educational environments on children's motor performance in China. METHOD: We conducted a cross-sectional study of 4001 preschool children selected from 160 classes. The children's motor performance was assessed using the Movement Assessment Battery for Children, 2nd edition (MABC-2). Home and educational environments were evaluated using validated checklists. The effects of home and educational environments on motor performance were analysed using mixed and multilevel logistic regression models. RESULTS: The results showed that one score increase in the outside space of the family home was positively associated with the increase in total test score (0.104) subtest score of aiming and catching (0.037), and balance (0.034) of the MABC-2, after adjusting for potential confounders (each p<0.05). Possession of motor toys at home and parental rearing behaviours were also related to total test score, manual dexterity, and balance (ß=0.022-0.104, each p<0.05). Space and furnishings, activity, and interaction in the classroom had a significant positive association with total test score (ß=0.069-0.201), and with subtest scores of manual dexterity, aiming and catching, and balance respectively (ß=0.115-0.206). Space and furnishings of classrooms and possession of toys in the household were protective factors for 'at risk' or significant poor performance (odds ratio 0.942-0.973, each p<0.05). INTERPRETATION: A permissive and accepting family and educational environment made a positive contribution to children's motor performance. Access to sufficient space and furnishings within the classroom, as well as toys in the family, were protective factors for poor motor performance. Future assistance is needed to support an advantageous environment in early childhood programmes in China.

Production of quercetin, kaempferol and their glycosidic derivatives from the aqueous-organic extracted residue of litchi pericarp with Aspergillus awamori.

Our previous work exhibited Aspergillus awamori fermentation of the litchi pericarp increased significantly antioxidant activity and DNA protection effect. In this present study, the litchi pericarp and its aqueous-organic extracted residues were fermented by A. awamori in order to elucidate the enhanced beneficial effects. The study identified that rutin which present in litchi pericarp could be deglycosylated to form quercetin and quercetin-3-glucoside after the fermentation. Application the standard compounds (rutin, quercetin 3-glucoside, quercetin, kaempferol-3-glucoside and kaempferol) further revealed the effective biotransformation by A. awamori fermentation. It was hypothesised that rutin was initially dehydroxylated to form kaempferol-3-rutinoside and then deglycosylated to form kaempferol-3-glucoside and kaempferol. To our best knowledge, it is the first report on dehydroxylated effect of polyphenols caused by A. awamori fermentation. Thus, A. awamori fermentation can provide an effective way to produce health benefiting value-added products from litchi pericarp in food industry.

Genetic structure of rice black-streaked dwarf virus populations in China.

Rice black-streaked dwarf virus (RBSDV) is a double-stranded RNA (dsRNA) virus belonging to the genus Fijivirus in the family Reoviridae. The genome of RBSDV consists of ten dsRNA segments. Although RBSDV has caused significant economic losses to rice and maize production in the past few years in China, its molecular diversity and evolution remain largely unknown. To elucidate the factor(s) underlying the evolution of RBSDV, we determined segment 8 (S8; carrying ORF8 encoding the minor core capsid protein) sequences of 101 samples and segment 10 (S10; carrying ORF10 encoding the major capsid protein) sequences of 103 samples. The results show that both ORF8 and ORF10 are under negative selection. The S8 of three isolates and S10 of two isolates are recombinants. The RBSDV population in China can be classified into three groups according to S8 sequences or into two groups according to S10 sequences, irrespective of host or geographical origin. Of the RBSDV isolates with both S8 and S10 sequences available, 17 are between-group reassortants and 30 are between-subgroup reassortants. The RBSDV subpopulations from different geographical regions and hosts show frequent gene flow within or between subpopulations. The RBSDV population from maize is in a state of expansion. In this study, no new emergent population was detected. Taken together, the results indicate that, in addition to recombination and negative selection, reassortment and gene flow are important factors that drive evolution of RBSDV in China.

Structural identification of (1→6)-α-d-glucan, a key responsible for the health benefits of longan, and evaluation of anticancer activity.

Longan is a delicious subtropical fruit with great health-beneficial effects. It has been utilized for disease prevention and health care since ancient age. To explore the chemicals responsible for the health benefits, water-soluble polysaccharides were extracted from longan flesh in this work. A pure polysaccharide (LPS1) was obtained through column purification. Analysis by gas chromatography showed LPS1 was a homopolysaccharide of glucose with glycosidic linkage of →6)-d-Glc-(1→. Nuclear magnetic resonance (NMR) spectra indicated that the configuration of anomeric carbon in glucose residual was α-form. The polysaccharide structure was further confirmed to be (1→6)-α-d-glucan by chemcial shift of C6. The molecular weight of LPS1 was calculated to be 108 kDa, which had 661 glucose residuals. Anticancer assay showed that LPS1 had anticancer activity against the growth of HepG2 cells to a certain extent. However, it did not show any cytotoxicity against MCF-7 breast cancer cells.