A novel prognostic signature based on smoking-associated genes for predicting prognosis and immune microenvironment in NSCLC smokers.

BACKGROUND: As a highly heterogeneous tumor, non-small cell lung cancer (NSCLC) is famous for its high incidence and mortality worldwide. Smoking can cause genetic changes, which leading to the occurrence and progress of NSCLC. Nevertheless, the function of smoking-related genes in NSCLC needs more research. METHODS: We downloaded transcriptome data and clinicopathological parameters from Gene Expression Omnibus (GEO) databases, and screened smoking-related genes. Lasso regression were applied to establish the 7-gene signature. The associations between the 7-gene signature and immune microenvironment analysis, survival analysis, drug sensitivity analysis and enriched molecular pathways were studied. Ultimately, cell function experiments were conducted to research the function of FCGBP in NSCLC. RESULTS: Through 7-gene signature, NSCLC samples were classified into high-risk group (HRG) and low-risk group (LRG). Significant difference in overall survival (OS) between HRG and LRG was found. Nomograms and ROC curves indicated that the 7-gene signature has a stable ability in predicting prognosis. Through the analysis of immune microenvironment, we found that LRG patients had better tumor immune activation. FCGBP showed the highest mutation frequency among the seven prognostic smoking related genes (LRRC31, HPGD, FCGBP, SPINK5, CYP24A1, S100P and FGG), and was notable down-regulated in NSCLC smokers compared with non-smoking NSCLC patients. The cell experiments confirmed that FCGBP knockdown promoting proliferation, migration, and invasion in NSCLC cells. CONCLUSION: This smoking-related prognostic signature represents a promising tool for assessing prognosis and tumor microenvironment in smokers with NSCLC. The role of FCGBP in NSCLC was found by cell experiments, which can be served as diagnostic biomarker and immunotherapy target for NSCLC.

Palladium-Catalyzed Inward Isomerization Hydroaminocarbonylation of Alkenes.

In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, the disfavored inward isomerization-hydrocarbonylation of alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed inward isomerization-hydroaminocarbonylation of unactivated alkenes and aniline hydrochlorides for the formation of synthetically valuable α-aryl carboxylic amides in high yields and high site-selectivities. The high efficiency of the reaction is attributed to a relay catalysis strategy, in which the Markovnikov-favored [PdH]-PtBu3 catalyst is responsible for inward isomerization, while the [PdH]-Ruphos catalyst is responsible for hydroaminocarbonylation of the resulting conjugated aryl alkenes. The reaction exhibits highly functional group tolerance and provides a new method for formal carbonylation of remote C(sp3)-H bond.

Transcriptomic analysis of uterine receptivity in Guinea pigs.

The mouse is a widely used animal model for studying human reproduction. However, the mice are eccentric implantation, and ovarian progesterone and estrogen are essential for implantation, which is different from human beings. Guinea pigs are unique from mice since, like humans, they are the interstitial implantation, and ovarian progesterone alone seems to be sufficient to allow for implantation. In this study, we firstly analyzed the gene expression profiles in the receptive uterus on day 5 of pregnancy compared to the pre-receptive uterus on day 3 of pregnancy in guinea pigs using the RNA-seq method. In total, 304 up-regulated and 475 down-regulated genes were identified. Gene Ontology and pathway enrichment analyses highlighted the importance of the inflammatory response in the receptive uterus. Through gene network analysis, we identified 24 hub genes, most of which were involved in regulating endometrial receptivity. In addition, we performed a cross-species comparison of differentially expressed genes associated with uterine receptivity. A total of 14 genes were shared among guinea pigs, humans, and mice. Furthermore, Fisher's exact test revealed that gene expression patterns of uterine receptivity were more similar between guinea pigs and humans than between mice and humans. Our study may contribute to increasing the knowledge of uterine receptivity in guinea pigs.

miR-450-5p and miR-202-5p Synergistically Regulate Follicle Development in Black Goat.

Follicle maturation is a complex biological process governed by numerous factors, and researchers have observed follicle development by studying the proliferation and apoptosis of follicular granulosa cells (GCs). However, the regulatory mechanisms of GCs proliferation and death during follicle development are largely unknown. To investigate the regulatory mechanisms of lncRNAs, mRNAs, and microRNAs, RNA sequencing (RNA-seq) and small RNA-seq were performed on large (>10 mm) and small follicles (<3 mm) of Leizhou black goat during estrus. We discovered two microRNAs, miR-450-5p and miR-202-5p, which can target GCs in goats and may be involved in follicle maturation, and the effects of miR-450-5p and miR-202-5p on ovarian granulosa cell lines were investigated (KGN). Using cell counting kit-8 (CCK-8) assays, 5-Ethynyl-2'-deoxyuridine (EdU) assay and flow cytometry, miR-202-5p overexpression could suppress the proliferation and induce apoptosis of GCs, whereas miR-450-5p overexpression induced the opposite effects. The dual-luciferase reporter assay confirmed that miR-450-5p could directly target the BMF gene (a BCL2 modifying factor), and miR-202-5p targeted the BCL2 gene. A considerable rise in phosphorylated Akt (p-AKT) protein was observed following the downregulation of BMF by miR-450-5p mimics. After BMF gene RNAi therapy, a notable elevation in p-AKT was detected. Mimics of miR-202-5p inhibited BCL2 protein expression, significantly decreasing p-AMPK protein expression. These results imply that during the follicular development in black goats, the miR-450-5p-BMF axis favored GC proliferation on a wide scale, while the miR-202-5p-BCL2 axis triggered GC apoptosis.

Molecular Cloning and Identification of NADPH Cytochrome P450 Reductase from Panax ginseng.

Ginseng (Panax ginseng C.A. Mey.) is a precious Chinese traditional medicine, for which ginsenosides are the most important medicinal ingredients. Cytochrome P450 enzymes (CYP450) and their primary redox molecular companion NADPH cytochrome P450 reductase (CPR) play a key role in ginsenoside biosynthesis pathway. However, systematic studies of CPR genes in ginseng have not been reported. Numerous studies on ginsenoside synthesis biology still use Arabidopsis CPR (AtCPR1) as a reductase. In this study, we isolated two CPR genes (PgCPR1, PgCPR2) from ginseng adventitious roots. Phylogenetic tree analysis showed that both PgCPR1 and PgCPR2 are grouped in classⅡ of dicotyledonous CPR. Enzyme experiments showed that recombinant proteins PgCPR1, PgCPR2 and AtCPR1 can reduce cytochrome c and ferricyanide with NADPH as the electron donor, and PgCPR1 had the highest enzymatic activities. Quantitative real-time PCR analysis showed that PgCPR1 and PgCPR2 transcripts were detected in all examined tissues of Panax ginseng and both showed higher expression in stem and main root. Expression levels of the PgCPR1 and PgCPR2s were both induced after a methyl jasmonate (MeJA) treatment and its pattern matched with ginsenoside accumulation. The present investigation suggested PgCPR1 and PgCPR2 are associated with the biosynthesis of ginsenoside. This report will assist in future CPR family studies and ultimately improving ginsenoside production through transgenic engineering and synthetic biology.

Palladium-Catalyzed Asymmetric Markovnikov Hydroxycarbonylation and Hydroalkoxycarbonylation of Vinyl Arenes: Synthesis of 2-Arylpropanoic Acids.

Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium-catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom-economical approach to an array of 2-arylpropanoic acids including several commonly used non-steroidal anti-inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2-arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio- and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate-limiting step.

Comprehensive analysis of mRNAs and miRNAs in the ovarian follicles of uniparous and multiple goats at estrus phase.

BACKGROUND: Fertility is an important economic trait in the production of meat goat, and follicular development plays an important role in fertility. Although many mRNAs and microRNAs (miRNAs) have been found to play critical roles in ovarian biological processes, the interaction between mRNAs and miRNAs in follicular development is not yet completely understood. In addition, less attention has been given to the study of single follicle (dominant or atretic follicle) in goats. This study aimed to identify mRNAs, miRNAs, and signaling pathways as well as their interaction networks in the ovarian follicles (large follicles and small follicles) of uniparous and multiple Chuanzhong black goats at estrus phase using RNA-sequencing (RNA-seq) technique. RESULTS: The results showed that there was a significant difference in the number of large follicles between uniparous and multiple goats (P < 0.05), but no difference in the number of small follicles was observed (P > 0.05). For the small follicles of uniparous and multiple goats at estrus phase, 289 differentially expressed mRNAs (DEmRNAs) and 16 DEmiRNAs were identified; and for the large follicles, 195 DEmRNAs and 7 DEmiRNAs were identified. The functional enrichment analysis showed that DE genes in small follicles were significantly enriched in ovarian steroidogenesis and steroid hormone biosynthesis, while in large follicles were significantly enriched in ABC transporters and steroid hormone biosynthesis. The results of quantitative real-time polymerase chain reaction were consistent with those of RNA-seq. Analysis of the mRNA-miRNA interaction network suggested that CD36 (miR-122, miR-200a, miR-141), TNFAIP6 (miR-141, miR-200a, miR-182), CYP11A1 (miR-122), SERPINA5 (miR-1, miR-206, miR-133a-3p, miR-133b), and PTGFR (miR-182, miR-122) might be related to fertility, but requires further research on follicular somatic cells. CONCLUSIONS: This study was used for the first time to reveal the DEmRNAs and DEmiRNAs as well as their interaction in the follicles of uniparous and multiple goats at estrus phase using RNA-seq technology. Our findings provide new clues to uncover the molecular mechanisms and signaling networks of goat reproduction that could be potentially used to increase ovulation rate and kidding rate in goat.

Efficient deletion of LoxP-flanked selectable marker genes from the genome of transgenic pigs by an engineered Cre recombinase.

Genetically modified (GM) pigs hold great promises for pig genetic improvement, human health and life science. When GM pigs are produced, selectable marker genes (SMGs) are usually introduced into their genomes for host cell or animal recognition. However, the SMGs that remain in GM pigs might have multiple side effects. To avoid the possible side effects caused by the SMGs, they should be removed from the genome of GM pigs before their commercialization. The Cre recombinase is commonly used to delete the LoxP sites-flanked SMGs from the genome of GM animals. Although SMG-free GM pigs have been generated by Cre-mediated recombination, more efficient and cost-effective approaches are essential for the commercialization of SMG-free GM pigs. In this article we describe the production of a recombinant Cre protein containing a cell-penetrating and a nuclear localization signal peptide in one construct. This engineered Cre enzyme can efficiently excise the LoxP-flanked SMGs in cultured fibroblasts isolated from a transgenic pig, which then can be used as nuclear donor cells to generate live SMG-free GM pigs harboring a desired transgene by somatic cell nuclear transfer. This study describes an efficient and far-less costly method for production of SMG-free GM pigs.

Role of mRNAs and long non-coding RNAs in regulating the litter size trait in Chuanzhong black goats.

Fecundity improvement is one of the most important objectives for goat breeders as it can considerably greatly increase production efficiency. The molecular mechanisms underlying fecundity in goats remain largely unknown. To explore the molecular and genetic mechanisms related to the fecundities and prolificacies in Chuanzhong black goats, we performed high-throughput RNA sequencing to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs (DElncRNAs and DEmRNAs, respectively) the ovaries of high-fecundity and low-fecundity goats; furthermore, we conducted functional annotation analyses to identify pathways of interest. Overall, 1,353 DEmRNAs and 168 DElncRNAs were identified. Quantitative real-time PCR (qRT-PCR) was performed to validate some randomly selected DElncRNAs and DEmRNAs. We found that two DElncRNAs ENSCHIT00000005909 and ENSCHIT00000005910 might positively influence the expression of the corresponding gene IL1R2 (upregulated in high-fecundity group), exerting co-regulative effects on the ovarian function, through which litter size might show variations. KEGG pathway analysis indicated that the DEmRNAs SRD5A2, LOC102191297 and LOC102171967 were significantly enriched in steroid hormone biosynthesis-this pathway was related to animal reproduction. To summarize, our findings expand the understanding pertaining to the biological functions of lncRNAs and contribute to the annotation of the goat genome; moreover, they should be helpful for further studying the role of lncRNAs in ovulation and lambing.

Orbitides isolated from flaxseed induce apoptosis against SGC-7901 adenocarcinoma cells.

Unique plant-derived cyclic peptides family exhibiting various key biological activities has great possibility for anticancer therapy. In this study, we investigated the effects of orbitides isolated from flax (Linum usitatissimum L.) on the growth of SGC-7901 cancer cells and the potential mechanism. Results showed that flaxseed orbitides killed off cancer cells by inducing apoptosis in a dose-dependent manner, which was confirmed by the appearance of nuclear shrinkage and DNA fragmentation, and the inhibitory effect was stronger than that of pure orbitide [1-9-NαC]-linusorb B2 or [1-9-NαC]-linusorb B3. Besides, the mitochondrial apoptosis pathway-related protein cytochrome C (Cyt C) was released from mitochondria to cytosol, associated with the activation of caspases 9 and 3, and the cleavage of PARP. Taken together, these results indicated that flaxseed orbitides induced apoptosis via the mitochondrial pathway, releasing Cyt C, increasing Bax/Bcl-2 ratio and elevating the expression of cleaved caspase 9 and 3 in SGC-7901 cells.

Transcriptomic and biochemical analysis of upland cotton (Gossypium hirsutum) and a chromosome segment substitution line from G. hirsutum × G. barbadense in response to Verticillium dahliae infection.

BACKGROUND: Verticillium wilt (VW), also known as "cotton cancer," is one of the most destructive diseases in global cotton production that seriously impacts fiber yield and quality. Despite numerous attempts, little significant progress has been made in improving the VW resistance of upland cotton. The development of chromosome segment substitution lines (CSSLs) from Gossypium hirsutum × G. barbadense has emerged as a means of simultaneously developing new cotton varieties with high-yield, superior fiber, and resistance to VW. RESULTS: In this study, VW-resistant investigations were first conducted in an artificial greenhouse, a natural field, and diseased nursery conditions, resulting in the identification of one stably VW-resistant CSSL, MBI8255, and one VW-susceptible G. hirsutum, CCRI36, which were subsequently subjected to biochemical tests and transcriptome sequencing during V991 infection (0, 1, and 2 days after inoculation). Eighteen root samples with three replications were collected to perform multiple comparisons of enzyme activity and biochemical substance contents. The findings indicated that VW resistance was positively correlated with peroxidase and polyphenol oxidase activity, but negatively correlated with malondialdehyde content. Additionally, RNA sequencing was used for the same root samples, resulting in a total of 77,412 genes, of which 23,180 differentially expressed genes were identified from multiple comparisons between samples. After Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on the expression profiles identified using Short Time-series Expression Miner, we found that the metabolic process in the biological process, as well as the pathways of phenylpropanoid biosynthesis and plant hormone signal transduction, participated significantly in the response to VW. Gene functional annotation and expression quantity analysis indicated the important roles of the phenylpropanoid metabolic pathway and oxidation-reduction process in response to VW, which also provided plenty of candidate genes related to plant resistance. CONCLUSIONS: This study concentrates on the preliminary response to V991 infection by comparing the VW-resistant CSSL and its VW-susceptible recurrent parent. Not only do our findings facilitate the culturing of new resistant varieties with high yield and superior performance, but they also broaden our understanding of the mechanisms of cotton resistance to VW.

Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans isolates from paediatric patients in China.

Cryptococcosis is a life-threatening mycosis primarily occurring in adult patients particularly those with immunosuppression such as HIV infection/AIDS. The number of reported cases of paediatric cryptococcosis has increased in the last decade around the world, including China. However, current information on the characteristics of cryptococcosis in children, particularly the genotypic diversity and antifungal susceptibility of the isolates, is limited. In the present study, a total of 25 paediatric isolates of Cryptococcus neoformans were genotyped using the ISHAM-MLST scheme. In vitro susceptibility to antifungal agents of the 22 isolates was tested using the CLSI M27-A3 method. Our analyses revealed that the genotypic diversity of C. neoformans isolates from Chinese paediatric patients was low, with ST 5 (80%) and ST 31 (12%) being the two major sequence types. Reduced susceptibility to fluconazole (FLU), 5-flucytosine (5-FC) and itraconazole (ITR) was observed among C. neoformans isolates from Chinese paediatric patients, particularly among the ST5 isolates, which was similar to observations made on C. neoformans isolates from Chinese adult patients. In addition, the majority of isolates (3/4, 75%) obtained from deceased patients showed decreased antifungal susceptibility, which indicates that further monitoring of antifungal susceptibility of Cryptococcus isolates is warranted in management of paediatric cryptococcosis.

PgMYB2, a MeJA-Responsive Transcription Factor, Positively Regulates the Dammarenediol Synthase Gene Expression in Panax Ginseng.

The MYB transcription factor family members have been reported to play different roles in plant growth regulation, defense response, and secondary metabolism. However, MYB gene expression has not been reported in Panax ginseng. In this study, we isolated a gene from ginseng adventitious root, PgMYB2, which encodes an R2R3-MYB protein. Subcellular localization revealed that PgMYB2 protein was exclusively detected in the nucleus of Allium cepa epidermis. The highest expression level of PgMYB2 was found in ginseng root and it was significantly induced by plant hormones methyl jasmonate (MeJA). Furthermore, the binding interaction between PgMYB2 protein and the promoter of dammarenediol synthase (DDS) was found in the yeast strain Y1H Gold. Moreover, the electrophoretic mobility shift assay (EMSA) identified the binding site of the interaction and the results of transiently overexpressing PgMYB2 in plants also illustrated that it may positively regulate the expression of PgDDS. Based on the key role of PgDDS gene in ginsenoside synthesis, it is reasonable to believe that this report will be helpful for the future studies on the MYB family in P. ginseng and ultimately improving the ginsenoside production through genetic and metabolic engineering.

Transcriptomics-based identification and characterization of 11 CYP450 genes of Panax ginseng responsive to MeJA.

Cytochromes P450 (CYP450s), a superfamily of mono-oxygenases, are essential to generate highly functionalized secondary metabolites in plants and contribute to the diversification of specialized triterpenoid biosynthesis in eudicots. However, screening and identifying the exact CYP450 genes in ginsenoside biosynthesis is extremely challenging due to existence of large quantities of members in CYP450 superfamily. Therefore, to screen the CYP450 genes involved in ginsenoside biosynthesis, transcriptome dataset of Panax ginseng was created in our previous work using the technique of the next-generation sequencing. On the basis of bioinformatics analysis, 16 putative CYP450 genes with significant differential expression were screened from the dataset and submitted to GenBank, in which 11 of them have been cloned. Methyl jasmonate (MeJA) was used as an elicitor to analyze the expression profiles of candidate CYP450 genes by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The results of qRT-PCR analysis revealed that the expression of some CYP450 genes were strongly induced by MeJA and showed different transcription levels at different treatment time points. Homology analysis indicated that each putative CYP450 protein of P. ginseng has a conserved domain consisting of E-E-R-F-P-R-G. The CYP450 genes were screened and cloned here to enrich the resources of CYP450 genes, and the results of bioinformatics analysis provided a foundation to further identify the function of CYP450s involved in ginsenoside biosynthesis. Furthermore, this study facilitated the construction of microbial cell factories for increasing the production of ginsenosides by means of metabolic engineering.

A Randomized Multicenter Clinical Trial of RPH With the Simplified Milligan-Morgan Hemorrhoidectomy in the Treatment of Mixed Hemorrhoids.

PURPOSE: To explore the safety and efficacy of Ruiyun procedure for hemorrhoids (RPH) or RPH with the simplified Milligan-Morgan hemorrhoidectomy (sMMH) in the treatment of mixed hemorrhoids. METHODS: This is a randomized, controlled, balanced, multicenter study of 3000 patients with mixed hemorrhoids. The outcomes and postoperative complications were compared between 5 types of surgeries. RESULTS: The efficacy rate was the highest in patients who received RPH+sMMH and decreased in the following order: patients who received RPH alone, MMH alone, procedure for prolapse and hemorrhoids (PPH) alone, and PPH+sMMH ( P < .05). The operation time was the shortest in patients who received RPH alone and increased in the following order: patients who received RPH+sMMH, PPH alone, MMH alone, and PPH+sMMH ( P < .01). The duration of postoperative hospitalization stay was the shortest in patients who received RPH alone and increased in the following order: PPH alone, RPH+sMMH, PPH+sMMH, and MMH alone ( P < .01). The incidence of postoperative hemorrhage, uroschesis, anal fissure, crissum hematoma or thrombosis, and anorectal stenosis was significantly lower in patients who received RPH+sMMH than in patients who received the other 4 types of surgical treatments ( P < .05, P < .01). No significant differences in postoperative rectovaginal fistula and anal incontinence were observed between the 5 groups of patients. CONCLUSIONS: RPH with or without simplified MMH can reduce the incidence of postoperative complications and improve the curative efficacy in the treatment of patients with mixed hemorrhoids.

[Treatment of Mixed Hemorrhoids by RPH with the Simplified Milligan-Morgan Surgery: a Multi-center, Randomized, Controlled Clinical Trial].

Objective To observe the safety and efficacy of RPH with the simplified. Milligan-Mor- gan(M-M) surgery on mixed hemorrhoids. Methods Totally 1 200 patients with mixed hemorrhoid were assigned to the control group(600 cases) and the treatment group(600 cases) according to randomized, parallel controlled,multi-center trial design. Patients in the control group received PPH with the simplified M-M surgery, and patients in the treatment group received RPH with the simplified M-M surgery. Postop- erative complications, operation time,the postoperative hospitalization days and the efficacy were ob- served. Results Compared with the control group, the numbers of postoperation hemorrhage, postop- erative uroschesis, anal fissure and anorectal stenosis in treatment group were decreased(P <0. 01 , P < 0. 05), operation time and the postoperative hospitalization days were decreased (P <0. 01 , P <0. 05 ), the cure rate for 3 and 12 months after operation were increased (P <0. 01, P <0. 05). Conclusions RPH with the simplified M-M surgery could reduce the incidence of postoperative complications,improve the clinical cure rate and the curative effect in treatment of mixed hemorrhoids.

Mechanical Strain Regulates Osteoblast Proliferation Through Ca2+-CaMK-CREB Signal Pathway.

Objective To investigate the effects of mechanical strain on Ca2+-calmodulin dependent kinase (CaMK)-cAMP response element binding protein (CREB) signal pathway and proliferation of osteoblasts.Methods Using a four-point bending device, MC3T3-E1 cells were exposed to mechanical tensile strains of 2500 µs and 5000 µs at 0.5 Hz respectively. The intracellular free Ca2+ ([Ca2+]i) concentration and calmodulin activity were assayed by fluorospectrophotometry, CaMK II ß, CREB, and phosphorylated (activated) CREB (p-CREB) were assessed by Western blot, and cells proliferation was assayed with MTT. Pretreatment with verapamil was carried out to block Ca2+ channel, and inhibitor U73122 was used to inhibit phospholipase C (PLC).Results Mechanical strains of 2500 µs and 5000 µs for 1 to 10 minutes both increased [Ca2+]i level of the cells. The 2500 µs strain, a periodicity of 1 h/d for 3 days, activated calmodulin, elevated protein levels of CaMK II ß and p-CREB, and promoted cells proliferation, which were attenuated by pretreatment of verapamil or U73122. The effects of 5000 µs strain on calmodulin, CaMK II ß, p-CREB and proliferation were contrary to 2500 µs strain.Conclusion The mechanical strain regulates osteoblasts proliferation through Ca2+-CaMK-CREB signal pathway via Ca2+ channel and PLC/IP3 transduction cascades.

Enhanced photovoltaic performance of organic/silicon nanowire hybrid solar cells by solution-evacuated method.

A method has been developed to fabricate organic-inorganic hybrid heterojunction solar cells based on n-type silicon nanowire (SiNW) and poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS) hybrid structures by evacuating the PEDOT:PSS solution with dip-dropping on the top of SiNWs before spin-coating (solution-evacuating). The coverage and contact interface between PEDOT:PSS and SiNW arrays can be dramatically enhanced by optimizing the solution-evacuated time. The maximum power conversion efficiency (PCE) reaches 9.22% for a solution-evacuated time of 2 min compared with 5.17% for the untreated pristine device. The improvement photovoltaic performance is mainly attributed to better organic coverage and contact with an n-type SiNW surface.

Increased prediction of right nonrecurrent laryngeal nerve in thyroid surgery using preoperative computed tomography with intraoperative neuromonitoring identification.

BACKGROUND: A nonrecurrent laryngeal nerve (NRLN) is a rare but potentially serious anatomical variant. Although the incidence is reported to be 0.3% to 1.3%, it carries a much higher risk of palsy during thyroid surgery. The objective of this study is to investigate the usefulness of computed tomography (CT) for preoperative identification and intraoperative neuromonitoring identification (IONM) of NRLN in thyroid cancer patients. METHODS: The preoperative neck CT scans from 1,574 patients who needed thyroid surgery were examined. Absence of the brachiocephalic artery (BCA) and the presence of arteria lusoria were defined as positive with NRLN. Systematic intraoperative neuromonitoring (IONM) was also carried out for these 1,574 patients to localize and identify NRLN. A negative electromyography (EMG) response from lower vagal stimulation but a positive EMG response from the upper position indicated the occurrence of an NRLN. RESULTS: Nine NRLN (0.57%) were intraoperatively identified out of the 1,574 patients, and no patient with a NRLN showed preoperative clinical symptoms related to NRLN. Prior to the operation, surgeons identified only seven suspected NRLN cases based on identification of arteria lusoria. But a review of CT scans revealed that all cases could be identified by vascular anomalies. All patients were successfully detected at an early stage of operation using intraoperative neuromonitoring (IONM). Postoperative vocal cord function was normal in all patients. CONCLUSIONS: CT of the neck is a reliable method for predicting NRLN before thyroid cancer surgery. However, some image features can be easily missed. Neurophysiology helps the surgeon to identify the NRLNs more precisely. Combining the two evaluation methods may decrease the incidence of nerve palsy, especially in cases of NRLN. Considering that CT is expensive, requires an X-ray, and achieves less information than ultrasound (US) concerning thyroid nodules, we suggest that applying US and IONM is more reasonable.

Clinical, pathological and gene expression profiling of estrogen receptor discordance in breast cancer.

BACKGROUND: Breast cancer (BC) is the world's largest tumor species in which hormone receptor-positive patients have relatively good prognosis. However, majority of patients will develop late resistance, one of the important factors is due to the loss of the original estrogen receptor (ER) expression. METHODS: We conducted this study in 115 patients with BC who experienced second biopsy at Jiangsu Province Hospital (JSPH) and divided patients into two subgroups ER + to - and ER + to + . First, clinicopathological characteristics between two groups were evaluated. Second, we explored candidate genes related to BC ER intratumor heterogeneity by applying next-generation sequencing (NGS) in 42 patients. Multi-omics integrative analysis of tumor transcriptomic, cancer-related pathway, diagnostic and prognostic value and immune profile were conducted. Besides, preliminary assay were also used to evaluate the correlation between KMT2C and ERα (ESR1) expression. The CCK-8, 5-Ethynyl-2'-deoxyuridine (EdU) assays, Transwell assays and the wound scratch tests were applied to explore the cellular interactions between KMT2C and BC. RESULTS: We find the histological type (p = 0.008) and disease-free survival (DFS) (p = 0.004) were significantly different in two subgroups. In Cox survival analysis, metastasis (Hazard ratio (HR) > 1, p = 0.007) and neo-adjuvant (HR < 1, p < 0.001) are independent prognostic factors of DFS. Besides, by analyzing NGS results, we found four genes KMT2C, FGFR19, FGF1 and FGF4 were highly mutated genes in ER + to - subgroup. Furthermore, the gene KMT2C displayed significant diagnostic value and prognostic value in BC and pan-cancer. In addition, a positive correlation between KMT2C expression and immune infiltrating levels of T cell CD4 + , macrophage and neutrophil was found. In the end, Western blot and RT-qPCR assay were used and found KMT2C and ERα (ESR1) expressions are strongly positive correlated in mRNA and protein level. Inhibition of KMT2C significantly reduced proliferation, invasion, and migration of MCF7 cells. CONCLUSION: People in two cohorts from JSPH presented different clinical characteristics and prognosis. The gene KMT2C may affect the progression of BC by regulating the molecular, epigenetic activity and immune infiltration. It may also serve as a novel prognostic biomarker for BC patients who underwent ER status converted from positive to negative.