Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage of HPV infection, progresses ...to intraepithelial neoplasia, and then develops into invasion and metastasis. Determining the complexity of tumor microenvironment (TME) can deepen our understanding of lesion progression and provide novel therapeutic strategies for CC. We performed the single-cell RNA sequencing on the normal cervix, intraepithelial neoplasia, primary tumor and metastatic lymph node tissues to describe the composition, lineage, and functional status of immune cells and mesenchymal cells at different stages of CC progression. A total of 59913 single cells were obtained and divided into 9 cellular clusters, including immune cells (T/NK cells, macrophages, B cells, plasma cells, mast cells and neutrophils) and mesenchymal cells (endothelial cells, smooth muscle cells and fibroblasts). Our results showed that there were distinct cell subpopulations in different stages of CC. High-stage intraepithelial neoplasia (HSIL) tissue exhibited a low, recently activated TME, and it was characterized by high infiltration of tissue-resident CD8 T cell, effector NK cells, Treg, DC1, pDC, and M1-like macrophages. Tumor tissue displayed high enrichment of exhausted CD8 T cells, resident NK cells and M2-like macrophages, suggesting immunosuppressive TME. Metastatic lymph node consisted of naive T cell, central memory T cell, circling NK cells, cytotoxic CD8+ T cells and effector memory CD8 T cells, suggesting an early activated phase of immune response. This study is the first to delineate the transcriptome profile of immune cells during CC progression using single-cell RNA sequencing. Our results indicated that HSIL exhibited a low, recently activated TME, tumor displayed immunosuppressive statue, and metastatic lymph node showed early activated phase of immune response. Our study enhanced the understanding of dynamic change of TME during CC progression and has implications for the development of novel treatments to inhibit the initiation and progression of CC.
Summary Background Because of the debate about whether second-generation antipsychotic drugs are better than first-generation antipsychotic drugs, we did a meta-analysis of randomised controlled ...trials to compare the effects of these two types of drugs in patients with schizophrenia. Methods We compared nine second-generation antipsychotic drugs with first-generation drugs for overall efficacy (main outcome), positive, negative and depressive symptoms, relapse, quality of life, extrapyramidal side-effects, weight gain, and sedation. Findings We included 150 double-blind, mostly short-term, studies, with 21 533 participants. We excluded open studies because they systematically favoured second-generation drugs. Four of these drugs were better than first-generation antipsychotic drugs for overall efficacy, with small to medium effect sizes (amisulpride −0·31 95% CI −0·44 to −0·19, p<0·0001, clozapine −0·52 −0·75 to −0·29, p<0·0001, olanzapine −0·28 −0·38 to −0·18, p<0·0001, and risperidone −0·13 −0·22 to −0·05, p=0·002). The other second-generation drugs were not more efficacious than the first-generation drugs, even for negative symptoms. Therefore efficacy on negative symptoms cannot be a core component of atypicality. Second-generation antipsychotic drugs induced fewer extrapyramidal side-effects than did haloperidol (even at low doses). Only a few have been shown to induce fewer extrapyramidal side-effects than low-potency first-generation antipsychotic drugs. With the exception of aripiprazole and ziprasidone, second-generation antipsychotic drugs induced more weight gain, in various degrees, than did haloperidol but not than low-potency first-generation drugs. The second-generation drugs also differed in their sedating properties. We did not note any consistent effects of moderator variables, such as industry sponsorship, comparator dose, or prophylactic antiparkinsonian medication. Interpretation Second-generation antipsychotic drugs differ in many properties and are not a homogeneous class. This meta-analysis provides data for individualised treatment based on efficacy, side-effects, and cost. Funding National Institute of Mental Health.
Ferroelectrics coupled with solar energy conversion are receiving intensive research interest. However, most ferroelectrics with a large remnant polarization can only harvest ultraviolet light in the ...solar spectrum. Herein, high‐quality silver niobate (AgNbO3) ceramics prepared by spark plasma sintering is reported with a bandgap of ≈2.75 eV and a long tail absorption until 800 nm, leading to outstanding photoelectric properties featured by the visible‐light response over 550 nm. Instantaneous photoresponse measurement using a 355 nm nanosecond pulse laser shows a fast response speed in nanoseconds. Moreover, the ceramic exhibits an intriguing photovoltaic effect under either electric poling or mechanical polishing. Both approaches have switchable characteristics and produce a stable photovoltage as well as photocurrent, while temperature dependence behavior reveals distinctions between ferroelectric polarization and ferroelastic strains in determining the photovoltaic properties. Piezoelectric force microscopy characterization further confirms distinctions between the underlying mechanisms. The electric poling induced photovoltaic effect stems from the aligned polarization involving the ferroelectric component, whereas the mechanical polishing induced photovoltaic effect is associated with the flexoelectricity induced by strain gradients. These results not only show AgNbO3 to be a promising material for photoelectric application but also deepen the understanding of the mechanism underlying ferroelectric photovoltaics.
The photoelectric and photovoltaic performances of AgNbO3 ceramics are comprehensively studied in this article. The spark plasma sintered AgNbO3 ceramic exhibits a bandgap ≈2.75 eV with a long tail absorption until 800 nm, leading to a significant photoelectric response in the visible‐light range. In addition, an intriguing photovoltaic effect is introduced to AgNbO3 ceramics by either electric poling or mechanical polishing.
Cervical cancer (CC) is the fourth leading cause of deaths in gynecological malignancies. Although the etiology of CC has been extensively investigated, the exact pathogenesis of CC remains ...incomplete. Recently, single-cell technologies demonstrated advantages in exploring intra-tumoral diversification among various tumor cells. However, single-cell transcriptome analysis (single-cell RNA sequencing scRNA-seq) of CC cells and microenvironment has not been conducted. In this study, a total of 20,938 cells from CC and adjacent normal tissues were examined by scRNA-seq. We identified four tumor cell subpopulations in tumor cells, which had specific signature genes with different biological functions and presented different prognoses. Among them, we identified a subset of cancer stem cells (CSCs) that was related to the developmental hierarchy of tumor progression. Then, we compared the expressive differences between tumor-derived endothelial cells (TECs) and normal ECs (NECs) and revealed higher expression of several metabolism-related genes in TECs. Then, we explored the potential biological function of ECs in vascularization and found several marker genes, which played a prior role in connections between cancer cells and ECs. Our findings provide valuable resources for deciphering the intra-tumoral heterogeneity of CC and uncover the developmental procedure of ECs, which paves the way for CC therapy.
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This study characterizes intra-tumor heterogeneity and developmental procedures of cervical cancer (CC) at single-cell resolution and provides valuable resources for therapeutic strategies of CC.
Introduction and hypothesis
Our objective was to assess the effectiveness of pelvic floor muscle training (PFMT) as a treatment for women with pelvic organ prolapse (POP) or as an adjunct to prolapse ...surgery.
Methods
Relevant literature sources were searched using databases including PubMed, Ovid, Web of Science, Scopus, ClinicalTrials.gov, EBSCO, CINAHL, the Cochrane Central Register of Controlled Trials, CNKI, VIP, Wanfang, and CBM until 5 July 2015. Eligible studies were restricted to randomized controlled trials (RCT). The available data were pooled using Review Manager version 5.2. For data deemed not appropriate for synthesis, a narrative overview was conducted.
Results
In total, 13 studies with 2,340 patients were included. Our results indicated women receiving PFMT gained a greater improvement than controls in prolapse symptom score mean difference (MD) −3.07, 95 % confidence interval (CI) −3.91 to −2.23 and POP stages risk ratio (RR) 1.70, 95 % CI 1.19–2.44. The number of women who said their prolapse was getting better was higher (RR 5.48, 95 % CI 2.19–13.72) and other discomfort syndromes, such as vaginal, bladder, and rectum, were lower in the PFMT groups than in controls. Meanwhile, women after PFMT had greater improvement in muscle strength and endurance but did not show a significant difference for further treatment needs. In addition, the results evaluating PFMT as an adjunct to prolapse surgery were inconclusive because of the variability in methods of measuring outcome.
Conclusions
Our meta-analysis demonstrated women who received PFMT showed a greater subjective improvement in prolapse symptoms and an objective improvement in POP severity.
Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and overt dementia, with amnesic MCI (aMCI) being the dominant subtype. This study aims to synthesise the ...prevalence results of MCI and aMCI in community-dwelling populations in China through a meta-analysis and systematic review.
The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol. English and Chinese studies published before 1 March 2020 were searched from ten electronic bibliographic databases. Two reviewers screened for relevance of the studies against the pre-defined inclusion and exclusion criteria and assessed the quality of the included studies using the Risk of Bias Tool independently. A random-effect model was adopted to estimate the prevalence of MCI and aMCI, followed by sub-group analyses and meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analyses.
A total of 41 studies with 112,632 participants were included in the meta-analyses. The Chinese community-dwelling populations over 55 years old had a pooled prevalence of 12.2% 95% confidence interval (CI): 10.6, 14.2% for MCI and 10.9% 95% CI, 7.7, 15.4% for aMCI, respectively. The prevalence of MCI increased with age. The American Psychiatric Association's Diagnostic tool (DSM-IV) generated the highest MCI prevalence (13.5%), followed by the Petersen criteria (12.9%), and the National Institute on Aging Alzheimer's Association (NIA-AA) criteria (10.3%). Women, rural residents, and those who lived alone and had low levels of education had higher MCI prevalence than others.
Higher MCI prevalence was identified in community-dwelling older adult populations in China compared with some other countries, possibly due to more broadened criteria being adopted for confirming the diagnosis. The study shows that aMCI accounts for 66.5% of MCI, which is consistent with findings of studies undertaken elsewhere.
PROSPERO CRD42019134686.
Simultaneously enhancing the thermal conductivity, insulation, and mechanical properties of high-density polyethylene (HDPE) composites is highly desired for electronic and electrical applications. ...In this research, HDPE/boron nitride (BN)/coconut shell charcoal (CSC) composites were prepared. Benefit from the synergistic effect between the multi-dimensional hybrid fillers, the prepared HDPE/BN/CSC composites exhibited enhanced comprehensive properties compared to the HDPE/BN composites and pure HDPE. In particular, as for HDPE/25BN/3CSC (25 wt% BN, 3 wt% CSC) nanocomposites compared to the pure HDPE, enhancements in in-plane thermal conductivity of 980.89%, normal thermal conductivity of 138%, and tensile strength of 18.91% were obtained, while higher volume resistivity and decomposition temperature were achieved. This work provides a simple but effective way for improving the thermal conductivity and comprehensive physical properties of HDPE composites.
•HDPE/BN/CSC composites were prepared.•High thermal conductivity of the HDPE/BN/CSC composites were achieved.•Thermal stability, mechanical properties, and insulation properties were all enhanced at appropriate CSC contents.
Healthy diets and physical exercise, two modifiable lifestyle factors, are protective against depression in older adults. This study aimed to investigate whether physical exercise may influence the ...associations of dietary habits with depression in Chinese community-dwelling older adults.
In the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey, 12,708 community-dwelling older adults aged ≥65 years were included for analyses. Older adults' dietary habits (including daily intake of food components such as fruits, vegetables, animal oil, and so on) and physical exercise were assessed. Depression was evaluated via the 10 item Center for Epidemiologic Studies Depression (CES-D-10) scale. The influences of physical exercise on the associations of dietary habits with depression were estimated using logistic regression models adjusted for confounders.
Older adults who took physical exercise had a significantly decreased probability of depression (adjusted OR = 0.73,
< 0.001). As for dietary habits, the intake of fruits, vegetables, eggs, nut products, mushrooms or algae, and vitamins were inversely associated with the prevalence of depression (adjusted ORs = 0.61-0.81;
-values: from <0.001 to 0.025), while animal oil was positively associated with it (adjusted OR = 1.52,
< 0.001). When stratified by physical exercise, older adults who ate fruits or vegetables had consistent decreased risk of depression, no matter whether they took physical exercise or not (adjusted ORs = 0.52-0.70), while the intake of eggs, nut products, and vitamins were inversely associated, and animal oil was consistently positively associated with depression only in older adults who did not take physical exercise (adjusted ORs = 0.79, 0.68, 0.63, and 1.67, respectively).
Physical exercise may conceal the potential protective effects of some healthy dietary habits in terms of depression and counteract the detrimental effects of the unhealthy habits. Some dietary habits may be considered as alternative protective measures for depression in community-dwelling older adults when physical exercise cannot be performed.
Successfully inhibiting a prepotent response tendency requires the attentional detection of signals which cue response cancellation. Although neuroimaging studies have identified important roles of ...stimulus-driven processing in the attentional detection, the effects of top-down control were scarcely investigated. In this study, scalp EEG was recorded from thirty-two participants during a modified Go/NoGo task, in which a spatial-cueing approach was implemented to manipulate top-down selective attention. We observed classical event-related potential components, including N2 and P3, in the attended condition of response inhibition. While in the ignored condition of response inhibition, a smaller P3 was observed and N2 was absent. The correlation between P3 and CNV during the foreperiod suggested an inhibitory role of P3 in both conditions. Furthermore, source analysis suggested that P3 generation was mainly localized to the midcingulate cortex, and the attended condition showed increased activation relative to the ignored condition in several regions, including inferior frontal gyrus, middle frontal gyrus, precentral gyrus, insula and uncus, suggesting that these regions were involved in top-down attentional control rather than inhibitory processing. Taken together, by segregating electrophysiological correlates of top-down selective attention from those of response inhibition, our findings provide new insights in understanding the neural mechanisms of response inhibition.
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