CRISPR-Cas13a system: A novel tool for molecular diagnostics

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a natural adaptive immune system of prokaryotes. The CRISPR-Cas system is currently divided into two classes and six types: types I, III, and IV in class 1 systems and types II, V, and VI in class 2 systems. Among the CRISPR-Cas type VI systems, the CRISPR/Cas13a system has been the most widely characterized for its application in molecular diagnostics, gene therapy, gene editing, and RNA imaging. Moreover, because of the trans-cleavage activity of Cas13a and the high specificity of its CRISPR RNA, the CRISPR/Cas13a system has enormous potential in the field of molecular diagnostics. Herein, we summarize the applications of the CRISPR/Cas13a system in the detection of pathogens, including viruses, bacteria, parasites, chlamydia, and fungus; biomarkers, such as microRNAs, lncRNAs, and circRNAs; and some non-nucleic acid targets, including proteins, ions, and methyl groups. Meanwhile, we highlight the working principles of some novel Cas13a-based detection methods, including the Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) and its improved versions, Cas13a-based nucleic acid amplification-free biosensors, and Cas13a-based biosensors for non-nucleic acid target detection. Finally, we focus on some issues that need to be solved and the development prospects of the CRISPR/Cas13a system

Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy

Additional file 2: Table S2. Stratified univariate analysis of DFS and OS between LG* and HG* in Chinese ESCC patients

Time scales of epidemic spread and risk perception on adaptive networks

Incorporating dynamic contact networks and delayed awareness into a contagion model with memory, we study the spreading patterns of infectious diseases in connected populations. It is found that the spread of an infectious disease is not only related to the past exposures of an individual to the infected but also to the time scales of risk perception reflected in the social network adaptation. The epidemic threshold $p_{c}$ is found to decrease with the rise of the time scale parameter s and the memory length T, they satisfy the equation $p_{c} =\frac{1}{T}+ \frac{\omega T}{a^s(1-e^{-\omega T^2/a^s})}$. Both the lifetime of the epidemic and the topological property of the evolved network are considered. The standard deviation $\sigma_{d}$ of the degree distribution increases with the rise of the absorbing time $t_{c}$, a power-law relation $\sigma_{d}=mt_{c}^\gamma$ is found

Outflow activities in the young high-mass stellar object G23.44-0.18

We present an observational study towards the young high-mass star forming region G23.44-0.18 using the Submillimeter Array. Two massive, radio-quiet dusty cores MM1 and MM2 are observed in 1.3 mm continuum emission and dense molecular gas tracers including thermal CH$_3$OH, CH$_3$CN, HNCO, SO, and OCS lines. The $^{12}$CO (2--1) line reveals a strong bipolar outflow originated from MM2. The outflow consists of a low-velocity component with wide-angle quasi-parabolic shape and a more compact and collimated high-velocity component. The overall geometry resembles the outflow system observed in the low-mass protostar which has a jet-driven fast flow and entrained gas shell. The outflow has a dynamical age of $6\times10^3$ years and a mass ejection rate $\sim10^{-3} M_{\odot}$ year$^{-1}$. A prominent shock emission in the outflow is observed in SO and OCS, and also detected in CH$_3$OH and HNCO. We investigated the chemistry of MM1, MM2 and the shocked region. The dense core MM2 have molecular abundances of 3 to 4 times higher than those in MM1. The abundance excess, we suggest, can be a net effect of the stellar evolution and embedded shocks in MM2 that calls for further inspection.Comment: 8 figures, 3 tables, accepted to MNRA

Использование индексного подхода для оценки надежности показателей паритета покупательной способности валют в Китае

The introduction of representative products in International Comparison Program makes the purchasing power parities (PPPs) a computable concept. The representative extent of the product list for the participating countries has important impacts on the reliability of PPPs and the global results. However, the measurement of representativeness and its induced biases in the estimated PPPs has not been carried out to our knowledge. Therefore, the paper designs a new index approach - Intra-National Assessment (INA), to assess the reliability of PPPs via representativeness. The approach considers the regional disparity and urban-rural differences from the lowest level of the product specifications to the GDP level. This bottom-up approach is applied to empirically assess the reliability of China’s PPPs in 2011 ICP. From the reliability degree perspective, the China’s PPP at GDP level is reliable, but the variation at main category is relatively larger. The PPP reliability of the lower levels function differently. The reliability of food and its subcategories are more reliable than any other categories because of detailed survey data sources. The reliability results of durable consumer goods, transport and communications, housing, machinery and equipment, and construction vary considerably. Further problems about the INA approach are discussed. Reliability implications in this study would be helpful for measuring the real size of China and the world economy.По мнению авторов, реализация требований репрезентативности при отборе товаров (услуг) - представителей в Программе международных сопоставлений (ПМС) является условием расчетов паритета покупательной способности валют (ППС). Репрезентативность включаемых в список товаров (услуг) - представителей (в участвующих в сопоставлениях странах) оказывает большое влияние на надежность оценок ППС и на глобальные результаты. Однако насколько нам известно, оценка репрезентативности товаров и ее влияние на искажения при исчислении ППС не проводилась. В данной работе предложен новый индексный подход - внутринациональная оценка надежности ППС на основе определения репрезентативности отбираемых товаров (услуг) - представителей. При таком подходе рассматриваются различия между регионами, а также между городской и сельской местностями, начиная с самого низкого уровня агрегирования до уровня ВВП. Подход «снизу-вверх» применяется для эмпирической оценки надежности ППС для Китая в ПМС 2011. Можно утверждать, что оценки ППС для Китая надежны на уровне ВВП, однако по мнению авторов, имеет место дифференциация в степени надежности применительно к отдельным составляющим конечного продукта. Оценки надежности ППС на более низких уровнях агрегирования различаются. Надежность оценок для категории «продукты питания» и ее подкатегорий обеспечивается наличием подробных данных. Оценки надежности показателей для категорий «товары длительного пользования», «транспорт и связь», «жилищные услуги», «машины и оборудование», «строительство» существенно различаются. Обсуждаются вопросы дальнейшего развития подхода на основе применения внутринациональной оценки. Результаты, полученные в данной работе, будут полезными для измерения реального размера как экономики Китая в частности, так и мировой экономики в целом

Knowledge level and influencing factors of sugar-sweetened beverages among Chinese adults aged 18-64 years in 2021

BackgroundExcessive intake of sugar-sweetened beverages (SSBs) is harmful to health. In recent decades, the consumption of SSBs by Chinese residents has increased rapidly, increasing the risk of death and burden of disease. ObjectiveTo analyze the knowledge level and influencing factors of SSBs for Chinese residents aged 18-64 years in 2021. MethodsA multi-stage cluster random sampling approach was used to conduct a questionnaire survey among residents aged 18-64 years in 302 survey sites across the country in 2021, and 98567 valid questionnaires were obtained. Four questions are about SSBs among the questionnaire's 5 dimensions. Respondents who answered 3 or more questions correctly were considered to have a basic understanding of SSBs. Frequency and weighted proportion were used for description. With individual as level 1 and resident council (village council) as level 2, a two-level logistic regression model was applied to examine the influencing factors. A null model was used to determine whether the two-level logistic regression model was appropriate. ResultsThe knowledge awareness rate of SSBs was 57.0% among the Chinese residents aged 18-64 years in 2021. The knowledge point with the lowest correct rate was "It is best to consume no more than 25 grams of added sugar per day" (22.6%), while the one with the highest correct rate was "Excessive intake of SSBs can increase the risk of obesity and diabetes" (81.1%). The results of the null model showed that SSBs knowledge level had a clustering effect at resident council (village council) level (t=25.00, P<0.0001), so a two-level model fit better than a one-level model. The results of the two-level logistic model revealed that residents who were female (OR=1.14, 95%CI: 1.11, 1.18) or working in medical and health (OR=1.36, 95%CI: 1.27, 1.45) and education institutions (OR=1.16, 95%CI: 1.07, 1.24) had a higher knowledge level compared to males or residents of other occupations. The knowledge level was lower among residents in central (OR=0.87, 95%CI: 0.77, 0.97) and western (OR=0.85, 95%CI: 0.75, 0.94) areas than in eastern areas. Those with chronic diseases (OR=0.81, 95%CI: 0.78, 0.84) and who did not know if they had a chronic disease (OR=0.75, 95%CI: 0.72, 0.78) had a lower knowledge level than those without chronic diseases. Compared with 18-24 years, the knowledge level was higher in ages 35-44 years (OR=1.07, 95%CI: 1.02, 1.12) and lower in ages 55-64 years (OR=0.92, 95%CI: 0.86, 0.97), and not different from the ages 25-34 years and 45-54 years. The knowledge level increased with the level of education, the trend was statistically significant (P＜0.001). ConclusionOnly about half of Chinese adults aged 18-64 years had a basic understanding of SSBs in 2021. The awareness rate of added sugar intake was low in particular. The knowledge levels of male, central and western, or less educated populations were even lower. Awareness of the negative health outcomes of SSBs was high among the population

Potentially Functional Variants of PLCE1 Identified by GWASs Contribute to Gastric Adenocarcinoma Susceptibility in an Eastern Chinese Population

BACKGROUND: Recent genome-wide association studies (GWAS) have found a single nucleotide polymorphism (SNP, rs2274223 A>G) in PLCE1 to be associated with risk of gastric adenocarcinoma. In the present study, we validated this finding and also explored the risk associated with another unreported potentially functional SNP (rs11187870 G>C) of PLCE1 in a hospital-based case-control study of 1059 patients with pathologically confirmed gastric adenocarcinoma and 1240 frequency-matched healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: We determined genotypes of these two SNPs by the Taqman assay and used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). We found that a significant higher gastric adenocarcinoma risk was associated with rs2274223 variant G allele (adjusted OR = 1.35, 95% CI = 1.14-1.60 for AG+GG vs. AA) and rs11187870 variant C allele (adjusted OR = 1.26, 95% CI = 1.05-1.50 for CG+CC vs. GG). We also found that the number of combined risk alleles (i.e., rs2274223G and rs11187870C) was associated with risk of gastric adenocarcinoma in an allele-dose effect manner (P(trend) = 0.0002). Stratification analysis indicated that the combined effect of rs2274223G and rs11187870C variant alleles was more evident in subgroups of males, non-smokers, non-drinkers and patients with gastric cardia adenocarcinoma. Further real-time PCR results showed that expression levels of PLCE1 mRNA were significantly lower in tumors than in adjacent noncancerous tissues (0.019±0.002 vs. 0.008±0.001, P<0.05). CONCLUSIONS/SIGNIFICANCES: Our results further confirmed that genetic variations in PLCE1 may contribute to gastric adenocarcinoma risk in an eastern Chinese population

Efficacy and safety of olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized controlled trials

BackgroundOlaparib has been proven for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This meta-analysis aims to comprehensively evaluate the efficacy and safety of the combination of olaparib and abiraterone in patients with mCRPC.MethodsThe literature in PubMed, Embase, and Cochrane Library up until April 27, 2023, was systematically searched. In the studies included in this meta-analysis, olaparib combined with abiraterone was compared with abiraterone combined with placebo.ResultsTwo randomized controlled trials involving a total of 938 patients were included. Analysis indicated that olaparib combined with abiraterone significantly prolonged radiographic progression-free survival (rPFS: relative risk [RR] 0.66, 95% confidence interval [CI] 0.55–0.79), time to secondary progression or death (PFS2: hazard ratio [HR] 0.72, 95% CI 0.56–0.93), time to first subsequent therapy or death (TFST: HR 0.75, 95% CI 0.63–0.89), time to second subsequent therapy or death (TSST: HR 0.73, 95% CI 0.58–0.93), and confirmed prostate-specific antigen (PSA) response (RR 1.14, 95% CI 1.05–1.24). However, no statistically significant differences were found in the overall survival (OS: HR 0.87 95% CI 0.70–1.09), objective response rate (ORR: RR 0.97, 95% CI 0.70–1.33), and incidence of total adverse events (RR 1.07, 95% CI 0.94–1.22). A notable detail that the combination of olaparib and abiraterone was associated with an increased incidence of high-grade anemia (RR 7.47, 95% CI 1.36–40.88).ConclusionOlaparib combined with abiraterone is effective for patients with mCRPC. However, combination therapy has treatment-related adverse events compared with monotherapy, and this could be improved in future treatment management.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432287

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy