Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI). Eleven polymorphisms in 9 genes, including ERCC1 rs11615 (OS), rs3212986 (ORR), XPA rs1800975 (ORR), XPD rs1052555 (OS, PFS), rs13181 (OS, PFS), XPG rs2296147 (OS), XRCC1 rs1799782 (ORR), XRCC3 rs861539 (ORR), GSTP1 rs1695 (ORR), MTHFR rs1801133 (ORR) and MDR1 rs1045642 (ORR), were found significantly associated with PBC treatment outcomes. These variants were mainly involved in DNA repair (EXCC1, XPA, XPD, XPG, XRCC1 and XRCC3), drug influx and efflux (MDR1), metabolism and detoxification (GSTP1) and DNA synthesis (MTHFR), and might be considered as potential prognostic biomarkers for assessing objective response and progression risk in NSCLC patients receiving platinum-based regimens.

The C-reactive protein/albumin ratio (CAR) has been shown to play a significant prognostic role in several cancers. We aimed to comprehensively explore the potential role of the CAR as a prognostic indicator in solid cancers. In this meta-analysis, we collected data from 10 studies that examined the association between serum CAR and overall survival in patients with cancer. This meta-analysis included 4592 tumor patients. The eligible studies were found through the PubMed and Web of Science databases updated on 6 Oct 2016. The pooled hazard ratio (2.01, 95% CI: 1.58-2.56, p < 0.001) indicated that high CAR yielded worse survival in different cancers. Subgroup analyses showed a significant association between CAR and prognosis, regardless of the cutoff value, cutoff value selection, treatment method, country, sample size, stage and cancer type. This meta-analysis suggests that CAR may be a potential prognostic marker in solid cancers. However, further large prospective studies should be conducted to explore the critical role of CAR in survival of cancer patients.

Controversial results of the association between maternal body mass index (BMI) and risk of autism spectrum disorder (ASD) in offspring were reported among several studies. This meta-analysis was conducted to estimate the overall association between maternal BMI and risk of ASD in offspring. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched until January 2016. Cohort and case-control studies addressing the association between maternal BMI and risk of ASD in offspring were included. We used random-effect models to estimate the summary relative risks (RRs), we also performed a dose-response meta-analysis to estimate the trend from the correlated log RR estimates across levels of BMI quantitatively. Totally, 6 cohort studies and 1 case-control study involving 8,403 cases and 509,167 participants were included for analysis. The summary RR (95% confidence interval) for ASD in offspring in relation to maternal underweight, overweight, and obesity vs. normal weight during pre-pregnancy or pregnancy, was 1.07 (0.93, 1.23), 1.28 (1.19, 1.36) and 1.36 (1.03, 1.78), respectively. A linear dose-response relationship was found, with a pooled RR of 1.16 (1.01, 1.33) for each 5 kg/m2. increment in maternal BMI. The present study suggests that excessive maternal BMI is associated with increased ASD risk in offspring.

Controversial results of the association between household physical activity and cancer risk were reported among previous epidemiological studies. We conducted a meta-analysis to investigate the relationship of household physical activity and cancer risk quantitatively, especially in dose-response manner. PubMed, Embase, Web of science and the Cochrane Library were searched for cohort or case-control studies that examined the association between household physical activity and cancer risks. Random-effect models were conducted to estimate the summary relative risks (RRs), nonlinear or linear dose-response meta-analyses were performed to estimate the trend from the correlated log RR estimates across levels of household physical activity quantitatively. Totally, 30 studies including 41 comparisons met the inclusion criteria. Total cancer risks were reduced 16% among the people with highest household physical activity compared to those with lowest household physical activity (RR = 0.84, 95% CI = 0.76-0.93). The dose-response analyses indicated an inverse linear association between household physical activity and cancer risk. The relative risk was 0.98 (95% CI = 0.97-1.00) for per additional 10 MET-hours/week and it was 0.99 (95% CI = 0.98-0.99) for per 1 hour/week increase. These findings provide quantitative data supporting household physical activity is associated with decreased cancer risk in dose-response effect.

Genome-wide association studies (GWAS) have identified two CHRNA3 polymorphisms (rs578776 and rs938682) associated with lung cancer risk. Furthermore, these polymorphisms were investigated and genotyped by PCR analysis. All eligible case-control studies published up to Mar 1st 2015 were identified by searching Pubmed and Embase database. Negative association between rs578776-T allele and risk of lung cancer was obtained without obvious heterogeneity (OR: 0.83, 95% CI: 0.79-0.86; p = 0.898 for Q test). Rs938682-C allele carriers had a 12% to 28% decreased risk. Genotype model analysis showed results of dominant model for rs578776 (OR with 95% CI: 0.839(0.718-0.981)), dominant model for rs938682 (OR with 95% CI: 0.778(0.663-0.912)) and homozygous model for rs938682 (OR with 95% CI: 0.767(0.708-0.831)) were statistically significant. Subgroup analysis indicated rs578776-T variant had protective effect in Smokers, Caucasians, two histology subgroups, and two match subgroups. Meanwhile, rs938682-C allele was associated with decreased risk in Smokers, Caucasians, Lung cancer, and two match subgroups. Meta-regression suggested ethnicity might be the major source of heterogeneity in allele model and homozygous model for rs938682. Moreover, smoking status might contribute to part of heterogeneity under allele model. In summary, this meta-analysis suggested both rs578776 and rs938682 were significantly associated with the susceptibility of lung cancer.

Association between allergic conditions and prostate cancer risk has been investigated for many years. However, the results from available evidence for the association are inconsistent. We conducted a meta-analysis to evaluate the relationship between allergic conditions (asthma, atopy, hay fever and "any allergy") and risk of prostate cancer. The PubMed and Embase databases were searched to screen observational studies meeting our meta-analysis criteria. Study selection and data extraction from included studies were independently performed by two authors. Twenty studies were considered eligible involving 5 case-control studies and 15 cohort studies. The summary relative risk (RR) for developing prostate cancer risk was 1.04 (95%CI: 0.92-1.17) for asthma, and 1.25 (95%CI: 0.74-2.10) for atopy, 1.04 (95%CI: 0.99-1.09) for hay fever, 0.96 (95%CI: 0.86-1.06) for any allergy. In the Subgroup and sensitivity analysis, similar results were produced. Little evidence of publication bias was observed. The present meta-analysis of observational studies indicates that no indication of an association between allergic conditions and risk of prostate cancer was found, and the meta-analysis does not support neither the original hypothesis of an overall cancer protective effect of allergic conditions, nor that of an opposite effect in the development of prostate cancer.

Previous studies have investigated the association of the rs1805087 A/G variant of Methionine synthase gene with the susceptibility to prostate cancer (PCa). Nevertheless, the conclusions remain divergent. We performed a systemic analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs) to assess Methionine synthase rs1805087 A/G variant and PCa risk. Furthermore, we utilized in silico analysis to investigate the relationship between Methionine synthase expression and the overall survival (OS) time. Totally, 10,666 PCa patients and 40,750 controls were included. We observed that Methionine synthase rs1805087 A/G variant is associated with an elevated risk of PCa (G-allele vs. A-allele: OR = 1.06, 95% CI = 1.01-1.11, P = 0.013; heterozygous model: OR = 1.08, 95% CI = 1.02-1.14, P = 0.009; dominant model: OR = 1.08, 95% CI = 1.02-1.14, P = 0.007). During stratified analysis, similar results were obtained in Asian populations, hospital-based, high quality studies and that with large sample size. Moreover, in silico analysis indicated the Methionine synthase expression is down-regulated in both young and old PCa subjects (P < 0.05). Compared with the normal subjects, the down-regulated expression of Methionine synthase was found in PCa cases with Gleason score 6 to 9. Our study showed that Methionine synthase rs1805087 A/G variant may be associated with susceptibility of PCa, especially in Asian populations, hospital-based studies and that with high quality and large sample size. Furthermore, Methionine synthase rs1805087 A/G variant may be related to the prognosis of PCa.

Sutures are an increasing focus of research in knee arthroplasty (KA). Whether knotless barbed sutures (KBS) are safe and efficient in KA remains controversial. The objective of our study is to compare the clinical outcomes of KA according to wound closure method: KBS versus knotted traditional sutures (KTS). To clarify this, we conducted a systematic review and meta-analysis. Nine articles involving 10 studies were included in this study. The dataset consisted of 1729 patients with 1754 KA. Among these, 814 patients' wounds were closed with KBS and 915 with KTS. Our analysis indicates that KBS is preferable for KA wound closure given its shorter wound closure time and lower total cost; postoperative Knee Society scores and complication rates were similar to those of surgeries using KTS. The subgroup analysis revealed that closure of arthrotomy with KBS appears to be associated with a lower risk of complications. This meta-analysis indicates that use of KBS in KA reduces operative time and cost. KBS is the preferred option for wound closures, including arthrotomy and reattachment of subcutaneous and subcuticular tissues. Given the possible biases, adequately powered and better-designed studies with longer follow-up are required to reach a firmer conclusion.

An important attribute of microRNAs is their potential use as disease biomarkers. However, such applications may be restricted because of unsatisfactory performance of the microRNA of interest. Owing to moderate correlation with spine T-score, miR-194-5p was identified as a potential biomarker for postmenopausal osteoporosis. Here, we determined whether medical examination could improve its characteristic as a biomarker for postmenopausal osteoporosis. We recruited 230 postmenopausal Chinese women to measure circulating levels of miR-194-5p, determine the spine bone status, and perform a 42-item medical examination. No obvious information redundancy was observed between miR-194-5p and any one item. However, on examining miR-194-5p alone, the sensitivity at fixed specificity of 0.9 (SESP=0.9) was 0.27, implying poor identification of at-risk individuals. Model integration of the microRNA and multiple medical items strengthened this property; in addition, model complexity greatly contributed to performance improvement. Using a model composed of two artificial neural networks, the ability of miR-194-5p to identify at-risk individuals significantly improved (SESP=0.9 = 0.54) when correlated with five medical items: weight, age, left ventricular end systolic diameter, alanine aminotransferase, and urine epithelial cell count. We present a feasible way to achieve a more accurate microRNA-based biomarker for a disease of interest.

The correlation between G388R or V10I polymorphisms of fibroblast growth factor receptor (FGFR) 4 gene and the risk of carcinoma has been investigated previously, but the results are contradictory. Odds ratios (ORs) with 95% confidence intervals (95%CIs), in silico tools, and immunohistochemical staining (IHS) were adopted to assess the association. In total, 13,793 cancer patients and 16,179 controls were evaluated in our pooled analysis. Summarization of all the studies showed that G388R polymorphism is associated with elevated susceptibility to cancer under homozygous comparison (OR = 1.21, 95%CI = 1.03-1.43, P = 0.020) and a recessive genetic model (OR = 1.21, 95%CI = 1.04-1.41, P = 0.012). In the stratification analysis by cancer type and ethnicity, similar findings were indicated for prostate cancer, breast cancer, and individuals of Asian descendant. Polyphen2 bioinformatics analysis showed that the G388R mutation is predicted to damage the protein function of FGFR4. IHS analysis indicated that FGFR4 expression is increased in advanced prostate cancer. These findings may guide personalized treatment of certain types of cancers. Up-regulation of FGFR4 may be related to a poor prognosis in prostate cancer.

Bacteriocins have antimicrobial activities against food-spoiling bacteria and food-borne pathogens. Paracin 1.7, a bacteriocin synthesized by Lactobacillus paracasei HD1-7 isolated from Chinese sauerkraut juice, was studied. Following partial purification with ammonium sulfate precipitation, CM Sepharose Fast Flow, and Sephadex G-10 chromatography, the molecular weight of Paracin 1.7 was about 10 kDa based on Tricine-SDS-PAGE results. A 2.87 fold purified bacteriocin was produced, reaching a final yield of 39.93% and the specific activity of 1.56 × 10(3) AU/mg. The N-terminal amino acid sequence of Paracin 1.7 was VSNTFFA, and the LC/LTQ results revealed that the N-terminal amino acid sequence was similar to that of ABC-type oligopeptide transport system protein and N-acetylmuramoyl-L-alanine amidase. Paracin 1.7 was sensitive to protease K, had antimicrobial activities at a broad pH range (3.0-8.0), and was heat resistant (121 °C for 20 min). Paracin 1.7 from Lactobacillus paracasei HD1-7 is a novel bacteriocin that has potential applications in food preservation.

Enterovirus 71 (EV71) infection causes hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children. There is thus an urgent need to find new treatments to control EV71 infection. In this study, we report potent inhibition of EV71 by a polyene antibiotic Amphotericin B. Amphotericin B profoundly diminished the expression of EV71 RNA and viral proteins in the RD cells and the HEK293 cells. As a result, EV71 production was inhibited by Amphotericin B with an EC50 (50% effective concentration) of 1.75 μM in RD cells and 0.32 μM in 293 cells. In addition to EV71, EV68 was also strongly inhibited by Amphotericin B. Results of mechanistic studies revealed that Amphotericin B targeted the early stage of EV71 infection through impairing the attachment and internalization of EV71 by host cells. As an effective anti-fungi drug, Amphotericin B thus holds the promise of formulating a novel therapeutic to treat EV71 infection.

The present study aims to investigate the genotype distribution of Human papillomavirus (HPV) and variations of HPV18 and HPV58 infection among 6538 females in Luoyang city during 2019-2021. The overall positive rate of females with HPV infection was 12.34%, with 9.74% were infected with single HPV and 2.60% with multiple HPVs. The prevalent rate of high-risk HPV (HR-HPV) was 9.85% and the top five HR-HPV genotypes were HPV52 (1.94%), HPV16 (1.93%), HPV58 (1.48%), HPV51 (1.02%) and HPVV39 (0.99%). Two peaks of HPV infections rates were observed in females aged ≤ 20 and 61-65 years old. To characterize mutations, 39 HPV18 and 56 HPV58 L1, E6 and E7 genes were sequenced and submitted to GenBank. In the HPV18 E6-E7-L1 sequences, 38 nucleotides changes were observed with 10/38 were non-synonymous mutations (5 in E6 gene, 1 in E7 gene and 4 in L1 gene). In the HPV58 E6-E7-L1 sequences, 53 nucleotides changes were observed with 23/53 were non-synonymous mutations (3 in E6 gene, 5 in E7 gene and 15 in L1 gene). Phylogenetic analysis based on L1 gene showed that 92.3% (36/39) of HPV18 isolates fell into sublineage A1 and 7.7% (3/39) belonged to A5. For HPV58, 75.0% (42/56) isolates belonged to sublineage A1 and 25.0% (14/56) were sublineage A2. There was no association between amino mutation and cervical lesions. The present study provides basic information about the distribution, genotypes and variations of HPV among females population in Luoyang city, which would assist in the formulation of HPV screening and vaccination programs and preventive strategies for HPV-attributable cancer in this region.

Farnesyl pyrophosphate synthase (FPS) is a key enzyme that catalyzes the formation of farnesyl pyrophosphate, the main initiator for rubber chain initiation in Hevea brasiliensis Muell. Arg. The transcriptional regulatory mechanisms of the FPS gene still not well understood. Here, a WRKY transcription factor designated HbWRKY27 was obtained by screening the latex cDNA library applied the HbFPS1 promoter as bait. HbWRKY27 interacted with the HbFPS1 promoter was further identified by individual Y1H and EMSA assays. HbWRKY27 belongs to group IIe WRKY subfamily which contains a typical WRKY domain and C-X5-CX23-HXH motif. HbWRKY27 was localized to the nucleus. HbWRKY27 predominantly accumulated in latex. HbWRKY27 was up-regulated in latex by ethrel, salicylic acid, abscisic acid, and methyl jasmonate treatment. Transient expression of HbWRKY27 led to increasing the activity of the HbFPS1 promoter in tobacco plant, suggesting that HbWRKY27 positively regulates the HbFPS1 expression. Taken together, an upstream transcription factor of the key natural rubber biosynthesis gene HbFPS1 was identified and this study will provide novel transcriptional regulatory mechanisms of the FPS gene in Hevea brasiliensis.

Obligate intracellular bacteria (obligates) belonging to Rickettsiales and Chlamydiales cause diseases in hundreds of millions of people worldwide and in many animal species. Lack of an efficient system for targeted mutagenesis in obligates remains a major impediment in understanding microbial pathogenesis. Challenges in creating targeted mutations may be attributed to essential nature of majority of the genes and intracellular replication dependence. Despite success in generating random mutations, a method that works well in creating mutations in specific genes of interest followed by complementation remains problematic for obligates and is a highly sought-after goal. We describe protocols to generate stable targeted mutations by allelic exchange in Ehrlichia chaffeensis, an obligate intracellular tick-borne bacterium responsible for human monocytic ehrlichiosis. Targeted mutations in E. chaffeensis were created to disrupt two genes, and also to restore one gene by another allelic exchange mutation leading to the restoration of transcription and protein expression from the inactivated gene and the recovered organisms also express mCherry, which distinguishes from the wild type. We expect that the methods developed are broadly applicable to other obligates, particularly to rickettsial pathogens, to routinely perform targeted mutations to enable studies focused on protein structure-function analyses, host-pathogen interactions and in developing vaccines.

The World Health Organization has declared ZIKA virus (ZIKV) a global public health emergency, prompted by the association of ZIKV infections with severe brain abnormalities in the human fetus. ZIKV preferentially targets human neuronal precursor cells (NPCs) in both monolayer and cortical brain organoid culture systems and stunts their growth. Although ZIKV is well recognized to cause microcephaly, there is no systematic analysis to demonstrate the effect of ZIKV on central nervous system (CNS) development, including brain malformations and spinal cord dysfunction. Here, we conducted a longitudinal analysis to show that a novel mouse model (infected in utero and monitored after birth until adulthood) recapitulates the effects of ZIKV infection affecting neural stem cells fate and leads to a thinner cortex and a smaller brain. Furthermore, we demonstrate the effect of ZIKV on spinal cord function. Specifically, we found significant reductions in neuron numbers in the anterior horn of grey matter of the spinal cord and muscle dystrophy with a significant decrease in forepaw grip strength in the ZIKV group. Thus, the established mouse model of ZIKV infection leading to abnormal CNS development will help to further advance our understanding of the disease pathogenesis.

It remains elusive if direct interspecies electron transfer (DIET) occurs in canonical syntrophy involving short-chain fatty acids oxidation. In the present study, we determined the effects of carbon nanomaterials on syntrophic oxidation of butyrate in two lake sediment enrichments and a defined coculture comprising Syntrophomonas wolfei and Methanococcus Maripaludis. After four continuous transfers of enrichment cultivation, Syntrophomonas dominated the bacterial populations in enrichments, and the dominated methanogens comprised Methanosarcina and Methanospirillum in one enrichment (from Weiming Lake) and Methanoregula and Methanospirillum in another (from Erhai Lake). Butyrate oxidation and CH4 production was significantly accelerated by carbon nanotubes (CNTs) in both enrichments. Replacement of CNTs by magnetite caused similar stimulating effect. For the defined coculture, two carbon nanomaterials, CNTs and reduced graphene oxide (rGO), were tested, both showed consistently stimulating effects on butyrate oxidation. Addition of kaolinite, an electric nonconductive clay mineral, however, revealed no effect. The test on M. maripaludis in pure culture showed no effect by rGO and a negative effect by CNTs (especially at a high concentration). Fluorescence in situ hybridization (FISH) and scanning electron microscopy (SEM) revealed that microbial cells were interwoven by CNTs forming cell-CNT mixture aggregates, and in case of rGO, cells were attached to surface or wrapped-up by rGO thin sheets. Collectively, our data suggest that the presence of conductive nanomaterials likely induces DIET in syntrophic butyrate oxidation.

Insecticidal proteins encoded by the truncated genes from Bacillus thuringiensis (Bt) in transgenic crops are released into soil mainly through root exudate and crop residues. In the present study, Bt Cry1Ac protein was hydrolyzed by pronase that was secreted by the soil bacterium Streptomyces griseus. Six peptides were identified as the products of enzymatic hydrolysis by nano liquid chromatography tandem mass spectrometry (LC-MS/MS). One of the six peptides was labeled with radioactive isotope iodine-125 and then purified. The 125I-peptide solution was irrigated to the rhizosphere soil of watermelon seedlings (Citrullus lanatus L.) and wheat seedlings (Triticum aestivum L.), which the two crops usually intercrop with cotton in China. Detection of radioactivity in both plant tissues within one hour proved adsorption, uptake and translocation of the peptide into watermelon and wheat seedlings. Three of the identified peptides were sprayed onto the seedling leaves of watermelon, wheat and maize (Zea mays L.) in the field or the growth chamber. No significant effects on plant growth were observed. These peptides also did not affect growth of organic phosphate-dissolving, nitrogen-fixing, and potassium-dissolving bacteria in the culture. This study provides a new view of GMO risk assessment methodology.

Sponge-bacteria interactions are very important due to their ecological and biological significance. To understand the impact of interactions between sponges and bacteria (both associated with and external to sponges) on sponge-associated microbial diversity, sponge metabolite profiles and bioactivity, we used a controlled aquarium system and designed an experimental approach that allows the study of sponge-bacteria interactions in a well-defined manner. To test the feasibility of this approach, this system was used to study the interaction between a sponge Aplysilla rosea and a marine bacterium commonly found in seawater, Vibrio natriegens. Sponge explants were exposed to V. natriegens, at 5 × 106 cfu/ml, and changes were monitored for 48 hours. Pyro-sequencing revealed significant shifts in microbial communities associated with the sponges after 24 to 48 hours. Both the control (sponge only without added bacteria) and Vibrio-exposed sponges showed a distinct shift in bacterial diversity and abundance with time. Vibrio exposure significantly increased bacterial diversity, the abundance of a number of taxa compared to control sponges. The result experimentally supports the notion of dynamic and concerted responses by the sponge when interacting with a bacterium, and demonstrates the feasibility of using this controlled aquarium system for the study of sponge-bacteria interactions.

Before implementing therapeutic genomic interventions for optimizing health in early life, comprehensive understanding of their effect on several traits across the life course is warranted. Abnorml  birthweight is associated with cardiometabolic disease risk in adulthood; however, the extent of genetic pleiotropy in the association has not been comprehensively investigated. We tested for pleiotropy and enrichment of functional loci between birthweight and 15 cardiometabolic disease traits (CMD). We found significantly abundant genetic pleiotropy (P < 3.3 × 10-3) and enrichment of functional annotations (P < 3.3 × 10-3) in loci influencing both birthweight and CMD. We did not observe consistent effect directions of pleiotropic loci on the traits. A total of 67 genetic loci, of which 65 loci have been reported in previous genome-wide association studies, were associated with both birthweight and CMD at a false discovery rate of 5%. Two novel loci were associated with birthweight and adult coronary artery disease (rs2870463 in CTRB1) and with birthweight and adult waist circumference (rs12704673 in CALCR). Both loci are known to have regulatory effects on expression of nearby genes. In all, our findings revealed pervasive genetic pleiotropy in early growth and adulthood cardiometabolic diseases, implying the need for caution when considering genetic loci as therapeutic targets.