Machine learning identifies characteristics molecules of cancer associated fibroblasts significantly correlated with the prognosis, immunotherapy response and immune microenvironment in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a highly lethal disease with a dramatic pro-fibrocytic response. Cancer-associated fibroblasts (CAFs) have been reported to play a key role in lung adenocarcinoma. Methods: Marker genes of CAFs were obtained from the Cell Marker website. Single sample gene set enrichment analysis (ssGSEA) was used for CAFs quantification. R and GraphPad Prism software were utilized for all analysis. Quantitative real-time PCR (qRT-PCR) was utilized to detect the RNA level of specific molecules. Results: Based on the ssGSEA algorithm and obtained CAFs markers, the LUAD patients with low- and high-CAFs infiltration were successfully identified, which had different response patterns to immunotherapy. Through the machine learning algorithm - LASSO logistic regression, we identified 44 characteristic molecules of CAFs. Furthermore, a prognosis signature consisting of seven characteristic genes was established, which showed great prognosis prediction ability. Additionally, we found that patients in the low-risk group might have better outcomes when receiving immunotherapy of PD-1, but not CTLA4. Also, the biological enrichment analysis revealed that immune response-related pathways were significantly associated with CAFs infiltration. Meanwhile, we investigated the underlying biological and microenvironment difference in patients with high- and low-risk groups. Finally, we identified that AMPD1 might be a novel target for LUAD immunotherapy. Patients with a high level of AMPD1 were correlated with worse responses to immunotherapy. Moreover, immunohistochemistry showed that the protein level of AMPD1 was higher in lung cancer. Results of qRT-PCR demonstrated that AMPD1 was upregulated in A549 cells compared with BEAS-2B. Meanwhile, we found that the knockdown of AMPD4 can significantly reduce the expression of CTLA4 and PDCD1, but not CD274 and PDCD1LG2. Conclusion: We comprehensively explored the role of CAFs and its characteristics molecules in LUAD immunotherapy and developed an effective signature to indicate patients prognosis and immunotherapy response. Moreover, AMPD1 was identified as a novel target for lung cancer immunotherapy.

Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies.

Background: Common vaccinations may have impacts on dementia risk, but current evidence is inconsistent. We therefore investigated the association between vaccinations and dementia risk by systematic review and meta-analysis approach. Methods: We conducted an extensive search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared the risk of dementia in vaccinated versus unvaccinated populations. The adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were pooled as measures. Results: Of the 9124 records initially retrieved, 17 studies with 1857134 participants were included in our analysis. The overall pooled results showed that vaccinations were associated with a 35% lower dementia risk (HR=0.65, 95% CI: 0.60-0.71, Poverall effect < 0.001; I2 = 91.8%, Pheterogeneity<0.001). All types of vaccination were associated with a trend toward reduced dementia risk, with rabies (HR=0.43), tetanus & diphtheria & pertussis (Tdap) (HR=0.69), herpes zoster (HR=0.69), influenza (HR=0.74), hepatitis A (HR=0.78), typhoid (HR=0.80), and hepatitis B (HR=0.82) vaccinations being significant. Individuals with more full vaccination types and more annual influenza vaccinations were less likely to develop dementia. Gender and age had no effect on this association. Conclusion: Routine adult vaccinations are associated with a significant reduction in dementia risk and may be an effective strategy for dementia prevention. Further research is needed to elucidate the causal effects of this association and the underlying mechanisms.

How Does Social Capital Affect Residents' Waste-Separation Behavior? Evidence from China.

The increasing amount of waste produced has been a challenge for human health and the environment, causing a call for effective waste management measures in which household waste separation is of great significance. Although an expanding body of literature has examined the impact of social capital on individual waste-separation behavior, few studies have explicitly discussed the endogeneity problem and the influence mechanisms. Accordingly, our study investigates the effect of social capital on waste-separation behavior and corresponding mechanisms using a national survey dataset of China. The study also reveals the heterogeneity of the influence of individual characteristics on waste-separation behavior. Our results demonstrate that social capital casts a significant positive impact on waste-separation behavior, providing opportunities for individuals' social learning and strengthening the reputation effect. The heterogeneous effects of social capital reveal that women, higher-educated individuals, and political party members present better waste-separation behavior. Besides, the impact of social capital varies between urban and rural areas and among different age groups. Our study provides empirical evidence for policy making of household waste-separation management in developing countries from the perspective of informal institutions.

The Unequal Effect of the COVID-19 Pandemic on the Labour Market and Income Inequality in China: A Multisectoral CGE Model Analysis Coupled with a Micro-Simulation Approach.

The COVID-19 pandemic had an unequal impact on the employment and earnings of different labourers, consequently affecting households' per capita income and income inequality. Combining a multisector computable general equilibrium model of China with a micro-simulation approach, this study aims to analyse the unequal effect of the COVID-19 pandemic on China's labour market and income inequality. The results confirm the unequal impact of the pandemic on the employment and earnings of different labourer types. Labourers who are female, live in urban areas, and have relatively low education levels would suffer greater losses in employment and earnings. The pandemic would reduce household per capita income by 8.75% for rural residents and 6.13% for urban residents. While the pandemic would have a larger negative impact on the employment and earnings of urban labourers, it would have a greater negative impact on the household per capita income of rural residents. Moreover, the per capita income of low-income households is more vulnerable to the pandemic, and the number of residents living below the poverty line would increase significantly. Thus, the pandemic would aggravate income inequality in China and threaten the livelihoods of poor families. This study could inform researchers exploring the distributional effect of the COVID-19 pandemic in developing countries.

Efficacy of electroacupuncture for the treatment of asthenozoospermia: A protocol for systematic review and meta-analysis.

INTRODUCTION: Infertility has affected millions of couples aged 15 to 44 years worldwide. Recently, some studies suggest that abnormal semen quality is the main cause of male infertility and asthenozoospermia accounts for 19% of the infertility of men. The situation has brought a huge burden to the patient with asthenozoospermia and society. Acupuncture is a part of traditional Chinese medicine. Electroacupuncture (EA) has gained in popularity. Although a positive effect of manual acupuncture and EA on sperm parameters has been documented in several studies, there still a lack of more solid evidence. We hope to provide a convincing study for EA. METHODS AND ANALYSIS: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of rESWT for patients with CP/CPPS will be included. We will evaluate the outcomes including NIH-CPSI, VAS, IPSS, IIEF-5, and conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on October 31st, 2021. CONCLUSIONS: EA for asthenospermia is a microtrauma surgery with less pain. EA can effectively improve sperm motility; however, its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the EA in patients with asthenospermia. ETHICS AND DISSEMINATION: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. PROTOCOL REGISTRATION NUMBER: INPLASY2020100071.

Molecular mechanisms underlying the function diversity of transcriptional factor IclR family.

The IclR family transcriptional factor is widespread and involves in diverse bacterial physio-pathological events, such as primary and secondary metabolism, virulence, quorum sensing, sporulation. Unlike other transcriptional factors which function as either activators or repressors, IclR can assume both role simutaneously. Its N-terminal domain possesses a helix-turn-helix DNA binding motif which can dimerize or tetramerize to bind target promoters, while the C-terminal domain is for the effector binding. The function of IclR varies with the effectors bound. Escherichia coli transcription factor IclR is the archetype of this family, which regulates the aceBAK operon responsible for the glyoxylate shunt. The sophisticated regulatory mechanisms underlying iclR was largely based on E. coli iclR. Information concerning the pathogen IclR, especially those of Mycobacterium tuberculosis is poor, and is pivotal to our understanding of its biology and development of new effective TB control measures.

Mycobacterium tuberculosis two-component systems and implications in novel vaccines and drugs.

Communication is vital for nearly all organisms to survive and thrive. For some particularly successful intracellular pathogens, a robust and precise signal transduction system is imperative for handling the complex, volatile, and harsh niche. The communication network of the etiology of tuberculosis, Mycobacterium tuberculosis (M.tb), namely two-component system (TCS), the eukaryotic-like Ser/Thr protein kinases(STPKs) system, the protein tyrosine kinase(PTK) system and the extracytoplasmic function σ(ECF-σ) system, determine how the pathogen responds to environmental fluctuations. At least 12 pair TCSs and four orphan proteins (three response regulators, Rv2884, Rv0260c, Rv0818, and one putative sensory transduction protein, Rv3143) can be found in the M.tb H37Rv genome. They regulate various aspects of M.tb, including virulence, dormancy, persistence, and drug resistance. This review focuses on the physiological roles of TCSs and the network of M.tb TCSs from a systems biology perspective. The implications of TCSs for better vaccine and new drug targets against tuberculosis are also examined.

The roles of pathogen small RNAs.

Regulatory small RNAs (sRNAs), also known as non-coding RNA, are not translated into proteins and widespread in prokaryotes and eukaryotes. sRNAs involve in multiple fundamental cellular events. They are emerging regulatory elements that are gaining momentum. Knowledge of sRNA largely originates from eukaryotes. Prokaryotic sRNAs, particularly those of pathogen are only recently explored. The main types, function, and methodology to predict pathogen sRNAs are summarized in this review. Special focus is sRNAs regulating pathogen gene expression, particularly that of Mycobacterium tuberculosis, which is hitherto the most successful pathogen afflicting mankind.