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The latest WHO guideline of CNS tumor defined a RELA fusion-positive ependymoma type with extremely poor prognosis, and the expression of L1CAM was correlated well with the presence of RELA fusion. However, the L1CAM protein expression in large sample gliomas other than ependymoma, its relationship with the RELA gene and its prognostic significance remained unknown. We examined the expression of L1CAM in 565 glioma cases (WHO grade I-IV). The L1CAM IHC-positive cases were selected to test RELA fusion with FISH break-apart probes. L1CAM was positive in 109 cases (19.29%) of all 565 glioma cases, with 18.27% in low-grade gliomas and 19.84% in high-grade gliomas, respectively. Unlike ependymoma, L1CAM protein expression was not correlated with the C11orf95-RELA fusion gene in other gliomas, but it had correction with the patient age (older than 45-year-old, p = 0.006), ATRX mutation (p = 0.003) and Ki67 (p = 0.007). High expression of L1CAM was an independent prognostic factor in our cohort. Further analysis demonstrated that L1CAM strong positive expression was significantly associated with poor prognosis in gliomas, both in our cohort (p < 0.001) and TCGA (p < 0.009) dataset. Although uncorrelated with C11orf95-RELA fusion, L1CAM was a significant poor prognostic marker in glioma patients. More aggressive treatment should be taken for these patients and L1CAM might be a promising therapeutic target in glioma. [ABSTRACT FROM AUTHOR]

Highlights • NaHS reduced the soluble cadmium fractions and increased the insoluble cadmium in salix. • NaHS reduced the distribution of Cd in salix organelles and vacuoles, but the Cd in the cell wall increased. • NaHS promotes the level of antioxidant enzyme activities and gene expression of salix. • NaHS increases the content of GSH and endogenous H 2 S in salix leaves and roots. Abstract Cadmium (Cd) is a highly toxic element for plant. In order to reveal the effects of NaHS on Cd uptake, physiological and molecular responses of salix to Cd toxicity, NaHS-mediated hydroponics of salix under Cd stress was performed. The addition of NaHS reduces the salix biomass reduction caused by Cd poisoning. NaHS did not obviously reduce the total Cd level absorbed by salix, but significantly reduced the soluble Cd fractions and increased the insoluble Cd fractions in salix leaves and roots. NaHS reduced the distribution of Cd in organelles and vacuoles and increased the distribution of Cd in the cell wall of salix leaves and roots. NaHS promotes the level of antioxidant enzyme activities and gene expression of salix, and reduces the accumulation of MDA and H 2 O 2 caused by Cd. NaHS increases the content of GSH and endogenous H 2 S in salix leaves and roots. The addition of NaHS can reduce the toxicity of Cd to salix without obviously reducing the Cd uptake by salix, thus improving the application of salix in phytoremediation to Cd. [ABSTRACT FROM AUTHOR]

• BjuSPL10c was expressed at a high level in flowers and up-regulated at reproductive stage. • Seven potential interactive proteins (BjuB025567, BjuA041065, BjuB033332, BjuA045694, BjuA027365, BjuA031237 and BjuA005619) were screened from B.juncea yeast library of flower buds at squaring stage. • Six (BjuB025567, BjuA041065, BjuB033332, BjuA045694, BjuA031237 and BjuA005619) of those proteins interacted with BjuSPL10c in vivo. • All of these six genes expressing interactive proteins were down-regulated in flowers. Brassica juncea var. tumida Tsen et Lee (Tumorous stem mustard) is a specific vegetable in China. Its tumorous stem can be consumed as fresh vegetable or produced pickle. In practice, early-bolting happens in around 15%, which inhibits B. juncea industry development. SPL is a plant specific transcription factor, plays important roles in flowering and gibberellins (GA) signaling. qRT-PCR assay found that BjuSPL10c was expressed at a high level in flowers and reproductive stage. To explore interactive proteins, BjuSPL10c was used as bait, finally seven proteins were screened and they are BjuB025567, BjuA041065, BjuB033332, BjuA045694, BjuA027365, BjuA031237 and BjuA005619. Further study confirmed that six of those proteins interacted with BjuSPL10c in vivo. qRT-PCR was conducted to understand mRNA expression levels of these six proteins in different tissues and development stages. The results showed that compared with root, mRNAs for all of these six genes were down-regulated in flowers. For different developmental stages, BjuB025567 and BjuA005619 were up-regulated at vegetative stage, down-regulated at reproductive stage; BjuB033332, BjuA045694 and BjuA031237 were significantly up-regulated at both vegetative and reproductive stages; BjuA041065 was showed "down-up-down" expression pattern. Taking all results together, BjuB025567, BjuA041065, BjuB033332, BjuA045694 and BjuA031237 may participate in flowering time regulation through interacting with BjuSPL10c in B. juncea. [ABSTRACT FROM AUTHOR]

Background: Glycogen synthase kinase 3 beta (GSK3β) is centrally involved in diverse cellular processes, including proliferation and apoptosis. This study aimed to investigate the influence of GSK3β expression on the prognosis of human non-small cell lung cancer (NSCLC) and the effects of GSK3β inhibition in NSCLC cell lines. Methods: Immunohistochemical and western blot assays were used to evaluate the GSK3β expression level in human NSCLC tissues. Lentiviral RNA interference was performed to inhibit the expression of GSK3β in the A549, H292, H1299 and SK-MES-1 cell lines. Cell survival, apoptosis and motility were evaluated in vivo and in vitro. Results: The levels of GSK3β were greater in NSCLC tissues (n = 211) than in control tissues (n = 194) (P<0.001). The 5-year follow-up analysis showed that positive GSK3β expression was indicative of poor prognosis (P = 0.006). Furthermore, knockdown of GSK3β in NSCLC cell lines suppressed cell proliferation, arrested tumor cells in G0/G1 phase, induced apoptosis and reduced cell motility. A xenograft model showed that the deregulation of GSK3β attenuated tumorigenesis, as confirmed by reduced cell proliferation based on Ki-67 and significantly increased apoptotic cell death. The inhibition of GSK3β had inconsistent effects on the expression of β-catenin, depending on the cell type examined. Conclusion: Aberrant expression of GSK3β serves as an independent marker of poor prognosis for NSCLC. The inhibition of GSK3β suppressed tumorigenesis by attenuating cell proliferation, increasing apoptosis and restraining cell motility. These results identify GSK3β as a tumor promoter and a potential therapeutic target in NSCLC. [ABSTRACT FROM AUTHOR]

Distant metastasis is the main cause of death in patients with clear cell renal carcinoma (ccRCC). The dysregulation of the tumor microenvironment is responsible for tumorigenesis and metastasis in ccRCC. The role of long non-coding RNAs in the tumor immune of ccRCC remains unclear. The present study screened differentially expressed protein-coding genes and non-coding genes between ccRCC and normal tissues based on three datasets. The commonly deregulated genes were used to identify distant metastasis-related long non-coding RNAs (lncRNAs) and prognostic lncRNAs. Pearson correlation analysis was used to identify immune-related lncRNAs. A competing endogenous RNA network was constructed and hub lncRNAs were identified. A total of 1650 coding genes, 821 lncRNAs and 62 miRNAs were commonly deregulated in the three datasets. A total of 408 lncRNAs associated with the overall survival of patients with ccRCC were identified. Among them, 82 lncRNAs were distant metastasis-related. Further analysis identified 52 lncRNAs associated with the immune pathway. Functional analyses concordantly demonstrated the role of the 52 lncRNAs in metastasis and tumor immunology. The ceRNA network analysis indicated lncRNA DSCR9 as the key lncRNA regulator. Univariate and multivariate analysis in two independent cohorts validated that DSCR9 could be an independent risk factor for the progression-free survival of patients with ccRCC. Further analyses indicated that DSCR9 might be associated with the immunotherapeutic response. reverse transcription-quantitative PCR demonstrated that the RNA expression level of DSCR9 was upregulated in ccRCC compared with normal kidney samples. The present study demonstrated the potential of LncRNA DSCR9 in assessing the prognosis and developing future immunotherapy for patients with metastatic ccRCC. [ABSTRACT FROM AUTHOR]

Cerebral ischemia/reperfusion (I/R) injury involves complex events of cellular and molecular processes. Previous studies suggest that a neurovascular unit (NVU) acts as an intricate network to maintain the neuronal homeostatic microenvironment. The present study established an NVU model for oxygen-glucose deprivation and reoxygenation (OGD/R) damage, trying to target the major components of the NVU using a coculture of rat neurons, astrocytes, and rat brain microvascular endothelial cells (rBMECs) to investigate the therapeutic effects of troxerutin and cerebroprotein hydrolysate injections (TCHis). The study observed that OGD/R downregulated the expressions of GAP-43, Claudin-5, and AQP-4 obviously detected by Western blotting and immunocytochemical analysis, respectively, while TCHi ameliorated the effect of OGD/R significantly. Meanwhile, TCHi alleviated the abnormalities of ultrastructure of neurons and rBMECs induced by OGD/R. Furthermore, both levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and cell adhesion molecules (VCAM-1 and ICAM-1) detected by ELISA in NVU supernatant were found elevated significantly through OGD/R, but TCHi ameliorated the trend. In addition, TCHi also mitigated the increase of proapoptotic factors (Bax, p53, and caspase-3) induced by OGD/R in NVU model statistically. All these findings demonstrated that TCHis played a protective role, which was reflected in anti-inflammation, antiapoptosis, and blood–brain barrier maintenance. The results of the study concluded that the NVU is an ideal target and TCHi acts as a neuroprotective agent against cerebral I/R injuries. [ABSTRACT FROM AUTHOR]

Baicalin (BA) is a major flavone from Scutellaria baicalensis Georgi and has showed significant curative effects in Parkinson's and Alzheimer's diseases. In the present study, we investigated the effects of BA on antineuroinflammation and related signaling cascade in lipopolysaccharide- (LPS-) induced BV-2 microglial model. The results showed that BA significantly attenuated inflammatory mediators (NO, iNOS, IL-1β, COX-2, and PGE2) and suppressed the expression of miR-155. More crucially, BA could regulate the expression of related proteins in Toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear factor κB (NF-κB) pathway and suppress the phosphorylation of mitogen-activated protein kinase (MAPK) family. In addition, molecular docking analysis indicated that BA binds to the amino acids Lie 63 and Tyr 65 of TLR4 by π - σ and π - π T-shaped interaction. Thus, BA suppressed the LPS-stimulated neuroinflammation in BV-2 microglia by blocking the TLR4-mediated signal transduction through TLR4/MyD88/NF-κB and MAPK pathways and inhibiting the miR-155 expression. Our findings demonstrated that BA could be a valuable therapeutic for the treatment of neuroinflammation and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding gene expression primarily found in plants and animals. Fungi produce microRNA-like RNAs (milRNAs) that are structurally similar to miRNAs and functionally important in various biological processes. The fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Banana Fusarium vascular wilt that threatens global banana production. It remains uncharacterized about the biosynthesis and functions of milRNAs in Foc. In this study, we investigated the biological function of milRNAs contributing to Foc pathogenesis. Within 24 hours post infecting the host, the Argonaute coding gene FoQDE2, and two Dicer coding genes FoDCL1 and FoDCL2, all of which are involved in milRNA biosynthesis, were significantly induced. FoQDE2 deletion mutant exhibited decreased virulence, suggesting the involvement of milRNA biosynthesis in the Foc pathogenesis. By small RNA sequencing, we identified 364 small RNA-producing loci in the Foc genome, 25 of which were significantly down-regulated in the FoQDE2 deletion mutant, from which milR-87 was verified as a FoQDE2-depedent milRNA based on qRT-PCR and Northern blot analysis. Compared to the wild-type, the deletion mutant of milR-87 was significantly reduced in virulence, while overexpression of milR-87 enhanced disease severity, confirming that milR-87 is crucial for Foc virulence in the infection process. We furthermore identified FOIG_15013 (a glycosyl hydrolase-coding gene) as the direct target of milR-87 based on the expression of FOIG_15013-GFP fusion protein. The FOIG_15013 deletion mutant displayed similar phenotypes as the overexpression of milR-87, with a dramatic increase in the growth, conidiation and virulence. Transient expression of FOIG_15013 in Nicotiana benthamiana leaves activates the host defense responses. Collectively, this study documents the involvement of milRNAs in the manifestation of the devastating fungal disease in banana, and demonstrates the importance of milRNAs in the pathogenesis and other biological processes. Further analyses of the biosynthesis and expression regulation of fungal milRNAs may offer a novel strategy to combat devastating fungal diseases. Author summary: The fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Banana Fusarium vascular wilt that threatens global banana production. However, knowledge about pathogenesis of Foc is limited. In particular, pathogenic regulatory mechanism of the microRNA like small RNAs (milRNAs) found in Foc is unknown. Here, we found that FoQDE2, an Argonaute coding gene, and two Dicer coding genes FoDCL1 and FoDCL2, which are involved in milRNA biosynthesis, are significantly induced during the early infection stage of Foc. The results suggested that the milRNAs biosynthesis mediated by these genes may play an active role in the infection process of Foc. Based on this assumption, we subsequently found a FoQDE2-dependent milRNA (milR-87) and identified its target gene. Functional analysis showed that FoQDE2, milR-87 and its target gene were involved in the pathogenicity of Foc in different degree. The studies help us gain insight into the pathogenesis with FoQDE2, milR-87, and its target gene as central axis in Foc. The identified pathogenicity-involved milRNA provides an active target for developing novel and efficient biocontrol agents against Banana Fusarium wilt. [ABSTRACT FROM AUTHOR]

Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC.Methods: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided.Results: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed.Conclusions: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients. [ABSTRACT FROM AUTHOR]

• A total of 85 candidate MATE gene family members were identified in the radish genome and comprised 4 groups by phylogenetic analysis of MATE genes in carmine radish with relation to other species. • In all of the examined tissues, the expression levels of 4 RsMATE genes (e.g. RsMATE31-b , RsMATE37-a , RsMATE13-c and RsMATE42-b) accumulated (RPKM > 5), suggesting that these genes are crucial for tissue development in radish. • The expression patterns of fifteen key RsMATE genes were investigated in 'XCB' (Xichangbai) and 'HX' (Hongxin) roots under Cd stress for different treatment times using quantitative real-time polymerase chain reaction (qRT-PCR), which showed compared to HX, RsMATE49-b , RsMATE33 and RsMATE26 transcripts were strongly altered at different time points in XCB responsive to Cd stress. Subsequently, RsMATE40-b , RsMATE16-b and RsMATE13- a genes were significantly expressed under ABA and NaCl stress treatments. Carmine radish (Raphanus sativus L.) is famous for containing a natural red pigment (red radish pigment) that grown in Fuling, Chongqing City, China. MATE (multidrug and toxic compound extrusion), as an integral member of the multidrug efflux transporter family, has various functions in plants. However, no information has been available about characteristics of the MATE gene family in carmine radish. In this study, total of 85 candidate MATE gene family members classified into 4 groups were identified and found to be widely and randomly distributed in different genome. Synteny analysis revealed that twenty-one segmental and ten tandem duplications acted as important regulators for the expansion of RsMATE genes. The Ka/Ks ratios of RsMATE indicated that RsMATE may have undergone intense purification in the radish genome. Cis-acting element analysis of RsMATE in the promoter region indicated that RsMATE were mainly related to the abiotic stress response and phytohormone. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that RsMATE40-b , RsMATE16-b and RsMATE13-a genes were significantly expressed under ABA (abscisic acid) and NaCl stress treatments respectively. In addition, the expression patterns of fifteen key RsMATE genes were investigated in 'XCB' (Xichangbai) and 'HX' (Hongxin) roots under Cadmium (Cd) stress for different treatment times using qRT-PCR, of those, RsMATE49-b , RsMATE33 and RsMATE26 transcripts were strongly altered at different time points in XCB responsive to Cd stress,compared to HX. This study will provide valuable insights for studying the functional characterization of the MATE gene in carmine radish and other plants. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common cancer among women worldwide. However, there is insufficient research that focuses on the expression and molecular mechanisms of microRNA (miR)-204-5p in BC. In the current study, data were downloaded from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena databases. They were then used to undertake a meta-analysis that leveraged the standard mean difference (SMD) and summarized receiver operating characteristic (sROC) to evaluate the expression of the precursor miR-204 and mature miR-204-5p in BC. Additionally, an intersection of predicted genes, differentially expressed genes (DEGs) from the TCGA database and the GEO database were plotted to acquire desirable putative genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses were performed to assess the potential pathways and hub genes of miR-204-5p in BC. A decreased trend in precursor miR-204 expression was detected in 1,077 BC tissue samples in comparison to 104 para-carcinoma tissue samples in the TCGA database. Further, the expression of mature miR-204-5p was markedly downregulated in 756 BC tissue samples in comparison to 76 para-carcinoma tissue samples in the UCSC Xena database. The outcome of the SMD from meta-analysis also indicated that the expression of miR-204-5p was markedly reduced in 2,306 BC tissue samples in comparison to 367 para-carcinoma tissue samples. Additionally, the ROC and sROC values indicated that miR-204-5p had a great discriminatory capacity for BC. In GO analysis, 'cell development', 'cell surface activity', and 'receptor agonist activity' were the most enriched terms; in KEGG analysis, 'endocytosis' was significantly enriched. Rac GTPase activating protein 1 (RACGAP1) was considered the hub gene in the PPI network. In conclusion, miR-204-5p may serve a suppressor role in the oncogenesis and advancement of BC, and miR-204-5p may have crucial functions in BC by targeting RACGAP1. [ABSTRACT FROM AUTHOR]

Background: Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma.Methods: In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.Findings: We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p<0·0001), disease-free survival (HR 3·51, 2·43-5·07; p<0·0001), and overall survival (HR 3·22, 2·18-4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status.Interpretation: The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.Funding: The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities. [ABSTRACT FROM AUTHOR]

In the Funding section, the grant number from the funder The National Science Foundation is listed incorrectly. Reference 1 Li M, Xie L, Wang M, Lin Y, Zhong J, Zhang Y, et al. (2022) FoQDE2-dependent milRNA promotes Fusarium oxysporum f. sp. cubense virulence by silencing a glycosyl hydrolase coding gene expression. [Extracted from the article]

DEAH-box helicase 33 (DHX33) has been implicated in ribosome biogenesis, mRNA translation and inflammation. However, the role of DHX33 in human cancer is rarely studied. Here, we showed that DHX33 expression was significantly increased in hepatocellular carcinoma (HCC), compared with the adjacent nontumorous tissues. In a cohort of 520 patients, DHX33 expression in HCC was closely associated with tumor size ( P = 0.007), serum AFP level ( P = 0.011), and tumor capsule ( P = 0.030). Kaplan–Meier analysis indicated high DHX33 expression was correlated with worse overall and disease-free survival, and higher recurrence rate. The prognostic value of DHX33 was further confirmed by stratified survival analysis. Multivariate analysis revealed DHX33 as an independent prognostic factor for poor overall survival (Hazard Ratio = 1.772, 95% confident interval: 1.451–2.165, P < 0.0001). Our data therefore suggest DHX33 is overexpressed in HCC and serves as a promising prognostic biomarker for this deadly disease. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory response syndrome induced by infection. T Lymphocytes play an important role in this disease. Transient receptor potential (TRP) channels and calcium-sensing receptors (CaSR) are expressed in lymphocytes to promote intracellular Ca 2+ release. However, data about the link between CaSR and TRP channels in septic T lymphocytes are few. In this study, by Ca 2+ imaging and Western blotting, we found that in septic rat peripheral blood T lymphocytes expressions of TRPC3 and TRPC6 proteins are higher. The SR/ER Ca 2+ ATPase inhibitor thapsigargin (TG) and CaSR agonist NPS R-568 also increased expressions of TRPC3 and TRPC6 proteins, which were reversed by PLC-IP 3 channel blocker U73122 and TRPC channels inhibitor SKF96365. By Ca 2+ imaging, we found that the depletion of ER Ca 2+ stores by TG elicited a transient rise in cytoplasmic Ca 2+ , followed by sustained increase depending on extracellular Ca 2+ . But, SKF96365, not Verapamil (L-type channels inhibitor) and NiCl 2 (Na + /Ca 2+ exchanger inhibitor), inhibited the relatively high [Ca 2+ ] i . NPS R-568 also resulted in the same effect, and the duration of [Ca 2+ ] i increase was eliminated completely by U73122 and was reduced in the absence of [Ca 2+ ] o . NPS R-568 and TG increased the apoptotic ratio of septic T lymphocytes, which can be suppressed by SKF96365 and U73122. These results suggested that CaSR activation promoted the expression of TRPC3 and TRPC6 and enhanced T lymphocytes apoptosis through PLC-IP 3 signaling pathway in sepsis. [ABSTRACT FROM AUTHOR]

• Contrastively the characterization of trichomes on Rosa roxburghii Tratt (RR) and R. sterilis S. D. Shi (RS). • Non-glandular trichomes were the main type of RR, while glandular and non-glandular were densely covered on RS. • The expression levels of the core trichome regulator genes varied depending on the trichome types. Trichomes are prevalent on the surfaces of many organs in Rosa and have an important impact on the edibility of the fruit. Here, the diversity, distribution, anatomical structure, and genetic regulation of trichomes in Rosa roxburghii Tratt. (RR) and R. sterilis S. D. Shi (RS) were explored. RS and RR are important commercial crops in China due to their nutritional and medicinal value; however, their consumption and utilization are limited, in part, by the abundance of trichomes on the fruit. Two main forms of trichomes were present in both germplasms, namely glandular and non-glandular trichomes. Non-glandular flagellate and acicular trichomes were observed on the sepals, fruit, major leaf veins, and pedicels of both germplasms, whereas non-glandular branched trichomes were present only on RS. Flagellate trichome exfoliation and acicular trichome lignification occurred gradually on the developing fruit. Capitate glandular and bowl-shaped glandular trichomes were abundant in RS, but were only observed on the major leaf veins of RR. Furthermore, some capitate glandular trichomes on the pedicels were found to develop into prickles in RS. Transmission electron microscopy indicated that vacuolation and in the extraplasmic space occurred in the glandular cells of the capitate trichomes at the late secretory stage. The prickles in RR and RS mainly consisted of lignin, suberin, cellulose, and hemicellulose, though the ratios of these constituents varied between species. The expression levels of several well-known core trichome regulatory genes varied depending on the trichome type. The transcript abundance of GL1 , GL2, and TTG1 was significantly higher in organs covered with acicular trichomes in both RR and RS, while the highest mRNA level of TRY was observed in the glabrous organs, suggesting a negative effect of this gene on trichome formation. Notably, the negative regulatory factor CPC was only highly expressed in the leaf mesophyll of RR, where no glandular trichomes were present, and the GL3 , PDF2-like, and CPC transcription factors co-regulated glandular trichome formation in RS. The expression of these genes peaked in the Fb3-stage buds of RR and B3-stage buds of RS, indicating different key phases for the regulation of trichome initiation. These data provide new insights into the genetic control of trichome formation in two Rosa species. [ABSTRACT FROM AUTHOR]

The severe damage to health and social burden caused by head and neck squamous cell carcinoma (HNSCC) generated an urgent need to develop novel anti-cancer therapy. Currently, drug repositioning has risen in responses to the proper time as an efficient approach to invention of new anti-cancer therapies. In the present study, we aimed to screen candidate drugs for HNSCC by integrating HNSCC-related pathways from differentially expressed genes (DEGs) and drug-affected pathways from connectivity map (CMAP). We also endeavored to unveil the molecular mechanism of HNSCC through creating drug-target network and protein-to-protein (PPI) network of component DEGs in key overlapping pathways. As a result, a total of 401 DEGs were obtained from TCGA and GTEx mRNA-seq data. Taking the intersection part of 27 HNSCC-related Kyoto Encyclopedia of Genes and Genomes pathways and 33 drug-affected pathways, we retained 22 candidate drugs corresponding to two key pathways (cell cycle and p53 signaling pathways) of the five overlapping pathways. Two of the hub genes (PCNA and CCND1) identified from the PPI network of component DEGs in cell cycle and p53 signaling pathways were defined as the critical targets of candidate drugs with increased protein expression in HNSCC tissues, which was reported by the human protein atlas (HPA) database and cBioPortal. Finally, we validated via molecular docking analysis that two drugs with unknown effects in HNSCC: MG-262 and bepridil might perturb the development of HNSCC through targeting PCNA. These candidate drugs possessed broad application prospect as medication for HNSCC. [ABSTRACT FROM AUTHOR]