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.

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.

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.

Although molecular data have revealed huge amounts of plant diversity, interpreting genetic diversity into entities corresponding to species is still challenging. Taxonomic ranking based on genetic distance has been used extensively, but the results have been open to dispute, while the application of the strategy to plants has been restricted to a small number of cases. Here, levels of internal transcribed spacer 2 (ITS2) sequence variation were examined from 17,203 sequences, representing 5,439 species in 113 genera of seed plants, to ascertain the association between species status and their molecular divergence. Our results showed that, although the average genetic distances of sister species (AGDS) varied among angiosperms, the mean value was 3.98% and seemed not to be influenced by higher-level hierarchical classification or life history. AGDS was also stable within the major lineages of the gymnosperms but at approximately half the value of angiosperms, except for the Gnetidae, where the AGDS almost equaled that of angiosperms. We found that these AGDS discrepancies, associated with the rates of molecular evolution, cannot simply be attributed to generation-time differences, and highlight the complex life histories of plants. Our results provide general ITS2 thresholds in seed plants, and suggest their use in species identification.

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.

Insects interact with the surrounding environment via chemoreception, and in social insects such as ants, chemoreception functions to mediate diverse behaviors including food acquisition, self/non-self recognition, and intraspecific communication. The invasive red imported fire ant, Solenopsis invicta, has spread worldwide, displaying a remarkable environmental adaptability. Odorant binding proteins (OBPs) are chemical compound carriers, involved in diverse physiological processes including odor detection and chemical transport. S. invicta contains a highly divergent 17-member OBP gene family, that includes an ant-specific expansion and the social organization implicated Gp-9 (OBP3) gene. A systematic gene expression analysis of the SiOBP repertoire was performed across social caste (workers, male and female alates), tissues (antennae, head, thorax, and abdomen), and developmental stages (egg, larvae, and pupae), revealing that although SiOBPs were expressed in the antennae, the major regions of expression were in the head and thorax across all castes, and the abdomen in male and female alates. SiOBPs were very highly expressed in female alates and at somewhat lower levels in male alates and workers. SiOBPs were differentially expressed, with unique signatures in various castes and tissues, suggesting functionality of SiOBPs beyond olfaction Expression patterns of SiOBP subgroups also showed relationships with their evolutionary relatedness.

Influenza A (H1N1) continues to be a major public health threat due to possible emergence of a more virulent H1N1 strain resulting from dynamic changes in virus adaptability consequent to functional mutations and antigenic drift in the hemagglutinin (HA) and neuraminidase (NA) surface proteins. In this study, we describe the genetic and evolutionary characteristics of H1N1 strains that circulated in India over a period of nine years from 2009 to 2017 in relation to global strains. The finding is important from a global perspective since previous phylogenetic studies have suggested that the tropics contributed substantially to the global circulation of influenza viruses. Bayesian phylogenic analysis of HA sequences along with global strains indicated that there is a temporal pattern of H1N1 evolution and clustering of Indian isolates with globally circulating strains. Interestingly, we observed four new amino acid substitutions (S179N, I233T, S181T and I312V) in the HA sequence of H1N1 strains isolated during 2017 and two (S181T and I312V) were found to be unique in Indian isolates. Structurally these two unique mutations could lead to altered glycan specificity of the HA gene. Similarly, sequence and structural analysis of NA domain revealed that the presence of K432E mutation in H1N1 strains isolated after 2015 from India and in global strains found to induce a major loop shift in the vicinity of the catalytic site. The findings presented here offer an insight as to how these acquired mutations could be associated to an improved adaptability of the virus for efficient human transmissibility.

For sponges (phylum Porifera), there is no reliable molecular protocol available for species identification. To address this gap, we developed a multilocus-based Sponge Identification Protocol (SIP) validated by a sample of 37 sponge species belonging to 10 orders from South Australia. The universal barcode COI mtDNA, 28S rRNA gene (D3-D5), and the nuclear ITS1-5.8S-ITS2 region were evaluated for their suitability and capacity for sponge identification. The highest Bit Score was applied to infer the identity. The reliability of SIP was validated by phylogenetic analysis. The 28S rRNA gene and COI mtDNA performed better than the ITS region in classifying sponges at various taxonomic levels. A major limitation is that the databases are not well populated and possess low diversity, making it difficult to conduct the molecular identification protocol. The identification is also impacted by the accuracy of the morphological classification of the sponges whose sequences have been submitted to the database. Re-examination of the morphological identification further demonstrated and improved the reliability of sponge identification by SIP. Integrated with morphological identification, the multilocus-based SIP offers an improved protocol for more reliable and effective sponge identification, by coupling the accuracy of different DNA markers.

Downy mildew caused by Plasmopara viticola is one of the most devastating diseases of grapevines worldwide. So far, the genetic diversity and origin of the Chinese P. viticola population are unclear. In the present study, 103 P. viticola isolates were sequenced at four gene regions: internal transcribed spacer one (ITS), large subunit of ribosomal RNA (LSU), actin gene (ACT) and beta-tubulin (TUB). The sequences were analyzed to obtain polymorphism and diversity information of the Chinese population as well as to infer the relationships between Chinese and American isolates. High genetic diversity was observed for the Chinese population, with evidence of sub-structuring based on climate. Phylogenetic analysis and haplotype networks showed evidence of close relationships between some American and Chinese isolates, consistent with recent introduction from America to China via planting materials. However, there is also evidence for endemic Chinese P. viticola isolates. Our results suggest that the current Chinese Plasmopara viticola population is an admixture of endemic and introduced isolates.

Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.

Rice (Oryza sativa) is a staple crop that supports half the world's population and an important monocot model system. Monocot leaf matures in a basipetal manner, and has a well-defined developmental gradient along the longitudinal axis. However, little is known about its transcriptional dynamics after leaf maturation. In this study, we have reconstructed a high spatial resolution transcriptome for the matured rice leaf by sectioning the leaf into seven 3-cm fragments. We have performed strand-specific Illumina sequencing to generate gene expression profiles for each fragment. We found that the matured leaf contains a longitudinal gene expression gradient, with 6.97% (2,603) of the expressed genes showing differentially expression along the seven sections. The leaf transcriptome showed a gradual transition from accumulating transcripts related to primary cell wall and basic cellular metabolism at the base to those involved in photosynthesis and energy production in the middle, and catabolic metabolism process toward the tip.

Glioblastoma (GBM), the most common type of primary malignant brain tumors harboring a subpopulation of stem-like cells (GSCs), is a fast-growing and often fatal tumor. Signal Transducer and Activator of Transcription 3 (STAT3) is one of the major signaling pathways in GSCs maintenance but the molecular mechanisms underlying STAT3 deregulation in GSCs are poorly defined. Here, we demonstrate that Inositol Polyphosphate-5-Phosphatase F (INPP5F), one of the polyphosphoinositide phosphatases, is differentially expressed in GSCs from glioma patients, and is identified as an inhibitor of STAT3 signaling via interaction with STAT3 and inhibition of its phosphorylation. Constitutively expressed INPP5F showed to suppress self-renewal and proliferation potentials of glioblastoma cells and reduced tumorigenicity of glioblastoma. In addition, loss of INPP5F gene in gliomas is significantly correlated with lower overall patient survivals. These findings suggest that INPP5F is a potential tumor suppressor in gliomas via inhibition of STAT3 pathway, and that deregulation of INPP5F may lead to contribution to gliomagenesis.

Sinomenine is a principal ingredient of traditional Chinese medicine, Sinomenium Acutum, which has been reported to have various pharmacological effects including anti-rheumatism and immunomodulation. This study examined the effects of sinomenine in rats that received chronic constriction injury (CCI), a model of peripheral neuropathic pain. CCI injury on the right sciatic nerve led to long-lasting mechanical hyperalgesia. Acute sinomenine treatment (10-40 mg/kg, i.p.) significantly and dose-dependently reversed mechanical hyperalgesia. In addition, the antinociceptive effects of sinomenine remained stable during repeated daily treatment for up to 2 weeks. Although sinomenine did not alter the duration of immobility in the forced swimming test in healthy animals, it dose-dependently reversed the increased immobility time in rats receiving CCI, suggesting that sinomenine attenuated chronic pain-induced depressive-like behavior. The antinociceptive effects of sinomenine were blocked by the GABAa receptor antagonist bicuculine. The doses of sinomenine studied here did not significantly alter the spontaneous locomotor activity. Together, these results suggested that sinomenine exerts significant antinociceptive effects for neuropathic pain via GABAa-mediated mechanism, which suggests that sinomenine may be useful for the management of chronic painful conditions such as neuropathic pain.