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Combination therapy with inhibitors of cytotoxic T lymphocyte-associated protein (CTLA)4 and programmed death (PD)-1 has demonstrated efficacy in cancer patients. However, there is little information on CTLA4 and PD-1 expression levels and their clinical significance across diverse cancers. In this study, we addressed this question by analyzing PD-1 and CTLA4 levels in 33 different types of cancer along with their prognostic significance using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia datasets. Liver hepatocellular carcinoma (LIHC) patients receiving cytokine-induced killer cell (CIK) immunotherapy at Sun Yat-sen University cancer center were enrolled for survival analysis. The correlation between PD-1/CTLA4 expression and cancer immunity was also analyzed. The results showed that PD-1 and CTLA4 transcript levels varied across cancer cell lines, with aberrant expression detected in certain cancer types; Kaplan-Meier analysis with the Cox proportional hazards model showed that this was closely related to overall survival in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, acute myeloid leukemialymphoma, uterine corpus endometrial carcinoma, and uveal melanoma in TCGA. High serum PD-1 and CTLA4 levels predicted better survival in LIHC patients receiving CIK therapy. PD-1 and CTLA4 levels were found to be significantly correlated with the degree of tumor cell infiltration using Tumor Immune Estimation Resource, Estimating Relative Subsets of RNA Transcripts, and Estimation of Stromal and immune Cells in Malignant Tumor Tissues Using Expression Data as well as with tumor-infiltrating lymphocyte marker expression; they were also related to tumor mutation burden, microsatellite instability, mismatch repair, and the expression of DNA methyltransferases in some cancer types. Gene set enrichment analysis of 33 cancer types provided further evidence for associations between PD-1/CTLA4 levels and cancer development and immunocyte infiltration. Thus, PD-1 and CTLA4 play important roles in tumorigenesis and tumor immunity and can serve as prognostic biomarkers in different cancer types., (Copyright © 2020 Liu, Kong, Huang, Wang, Li and Chen.)

Little is known about the effect of training on genetic markers for mitochondrial biogenesis in elite athletes. We tested the hypothesis that low-volume sprint interval exercise (SIE) would be as effective as high-volume interval exercise (IE). Ten male cyclists competing on national elite level (W (max) 403 ± 13 W, VO(2peak) 68 ± 1 mL kg(-1) min(-1)) performed two interval exercise protocols: 7 × 30-s "all-out" bouts (SIE) and 3 × 20-min bouts at ~87% of VO(2peak) (IE). During IE, the work was eightfold larger (1,095 ± 43 vs. 135 ± 5 kJ) and the exercise duration 17 times longer (60 vs. 3.5 min) than during SIE. Muscle samples were taken before and 3 h after exercise. The mRNA of upstream markers of mitochondrial biogenesis [peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1α), PGC-1α-related coactivator (PRC) and peroxisome proliferator-activated receptor δ (PPARδ)] increased to the same extent after SIE and IE (6-, 1.5- and 1.5-fold increase, respectively). Of the downstream targets of PGC-1α, mitochondrial transcription factor A (Tfam) increased only after SIE and was significantly different from that after IE (P < 0.05), whereas others increased to the same extent (pyruvate dehydrogenase kinase, PDK4) or was unchanged (nuclear respiratory factor 2, NRF2). We conclude that upstream genetic markers of mitochondrial biogenesis increase in a similar way in elite athletes after one exercise session of SIE and IE. However, since the volume and duration of work was considerably lower during SIE and since Tfam, the downstream target of PGC-1α, increased only after SIE, we conclude that SIE might be a time-efficient training strategy for highly trained individuals.

A bacterial strain with high cellulase activity (0.26 U/ml culture medium) was isolated from hot spring, and classified and named as B. subtilis DR by morphological and 16SrDNA gene sequence analysis. A thermostable endocellulase, CelDR, was purified from the isolated strain. The optimum temperature of the enzyme reaction was 50 degrees C, and CelDR retained 70% of its maximum activity at 75 degrees C after incubation for 30 min. The putative gene celDR, consisting an open reading frame (ORF) of 1,524 nucleotides and encoding a protein of 508 amino acids with a molecular weight of 55 kDa, was purified from B. subtilis DR and cloned into pET-28a for expression. The cellulase production in E. coli BL21 (DE3) was enhanced to approximately three times that of the wild-type strain.

Ginkgo biloba L. is a valuable medicinal plant known for its high content of flavonoids and terpenoids in the leaves of young trees. Pruning can increase leaf yield in ginkgo plantations; however, it is unclear how the intensity of pruning affects leaf yield and quality. In addition, G. biloba exhibits low cutting rooting rates, which limits its efficiency in asexual propagation. In our study, we compared consecutive pruning with varying levels of intensity, including top pruning, light pruning, and heavy pruning, to evaluate the effects of pruning on leaf yield and cutting rooting. The results showed that these three pruning methods all contributed to an increase in the number of new branches, the leaf weight, and the flavonoid content in five-year-old trees. Among them, the effect of light pruning was the best, with a 150% increase in branch number, a 130% increase in leaf weight, and a 40.6% increase in flavonoid content. The secondary pruning further increased leaf area by 22.3%, indicating that secondary pruning further enhanced the rejuvenation of plants and increased leaf yield. At the transcriptional level, pruning can significantly change the expression of genes related to bud sprouting, resulting in a particularly significant increase in SHR expression in the buds. Pruning also promoted the expression of important genes related to flavonoid synthesis, including chalcone synthase (CHS), flavonoid 3′-hydroxylase (F3′H), flavonol synthase (FLS), and dihydroflavonol reductase (DFR). Furthermore, we demonstrated a significant increase in the rooting rate of these second-pruned branch cuttings and screened the optimal hormone ratio for rooting, which is 1.5 μM MeJA + 400 mg/L NAA + 100 mg/L Uniconazole-P. These results suggest that secondary pruning can effectively rejuvenate plants to promote cutting rooting in G. biloba. This method can not only be used to improve the yield and quality of ginkgo leaves, but also for cutting propagation.

Ginkgo biloba is a highly valuable medicinal plant known for its rich secondary metabolites, including flavonoids. Zinc oxide nanoparticles (ZnO-NPs) can be used as nanofertilizers and nano-growth regulators to promote plant growth and development. However, little is known about the effects of ZnO-NPs on flavonoids in G. biloba. In this study, G. biloba was treated with different concentrations of ZnO-NPs (25, 50, 100 mg/L), and it was found that 25 mg/L of ZnO-NPs enhanced G. biloba fresh weight, dry weight, zinc content, and flavonoids, while 50 and 100 mg/L had an inhibitory effect on plant growth. Furthermore, quantitative reverse transcription (qRT)-PCR revealed that the increased total flavonoids and flavonols were mainly due to the promotion of the expression of flavonol structural genes such as GbF3H, GbF3′H, and GbFLS. Additionally, when the GbF3H gene was overexpressed in tobacco and G. biloba calli, an increase in total flavonoid content was observed. These findings indicate that 25 mg/L of ZnO-NPs play a crucial role in G. biloba growth and the accumulation of flavonoids, which can potentially promote the yield and quality of G. biloba in production.

Autumn leaf senescence and coloration is a complex process and a striking natural phenomenon. Here, through biology approach integrating transcriptomic analyses in Ginkgo biloba, we determined that the content of chlorophyll decreased during leaf senescence, while carotenoid components increased until late October in the turning stage (TS) and then decreased in the yellow leaf stage (YS). Simultaneously, chlorophyll biosynthesis genes exhibited significantly lower expression levels while chlorophyll degradation genes showed increased expression from the green leaf stage (GS) to YS. However, carotenoid biosynthesis-related genes showed enhanced expression, especially in TS. An analysis of the expression of genes related to senescence demonstrated that the expression levels of most abscisic acid- and jasmonic acid-related genes, autophagy, WRKY, and NAC genes increased, whereas cytoskeleton-, photosynthesis-, and antioxidation-related genes decreased from GS to YS. Furthermore, G. biloba seedlings exogenously treated with abscisic acid, jasmonic acid, or ultraviolet-B radiation all showed obvious color variation and senescence symptoms. We used these exogenously seedlings to further validate the function of several genes involved in chlorophyll biosynthesis and senescence. Taken together, these results contribute to the elucidation of the molecular mechanisms of leaf coloration and senescence in G. biloba as well as in the identification of candidate genes involved in this process.

Extensive studies have been carried out on chloroplast gene expression and chloroplast development; however, the regulatory mechanism is still largely unknown. Here, we characterized Pigment-Defective Mutant4 (PDM4), a P-type PPR protein localized in chloroplast. The pdm4 mutant showed seedling-lethal and albino phenotype under heterotrophic growth conditions. Transmission electron microscopic analysis revealed that thylakoid structure was totally disrupted in pdm4 mutant and eventually led to the breakdown of chloroplasts. The levels of several chloroplast- and nuclear-encoded proteins are strongly reduced in pdm4 mutant. Besides, transcript profile analysis detected that, in pdm4 mutant, the expression of plastid-encoded RNA polymerase-dependent genes was markedly affected, and deviant chloroplast rRNA processing was also observed. In addition, we found that PDM4 functions in the splicing of group II introns and may also be involved in the assembly of the 50S ribosomal particle. Our results demonstrate that PDM4 plays an important role in chloroplast gene expression and chloroplast development in Arabidopsis.

Purpose: Metabolic alterations are crucial for tumor progression and response to therapy. The comprehensive model of combined central carbon metabolism–associated genes that contribute to the outcomes of glioma and astrocytoma is not well understood.Method: We studied the profiles of 63 genes involved in central carbon metabolism in 514 relatively low-grade glioma patients. The different distributions of gene expression in gliomas and astrocytoma were identified. The differential gene expression between each cohort and the correlations with prognosis were detected. Finally, we built a tentative model to detect the prognostic roles of carbon metabolism–associated genes in astrocytoma.Result: Two primary clusters and four subclusters with significantly different overall survival were identified in low-grade glioma. The differences of histological diagnoses, grade, tumor site, and age were detected between each cluster. Comparing with other histological types, patients with astrocytoma exhibited the worst prognosis. Between astrocytoma patients with poor and favorable prognoses, expression profiles of 11 genes were significantly discrepant. We detected that 18 genes were respectively correlated with overall survival in astrocytoma; moreover, four genes (RAF1, AKT3, IDH1, and FGFR1) were detected as dependent variables for the prediction of the survival status of astrocytoma patients and were capable to predict the survival.Conclusion: Central carbon metabolism–associated genes are differentially expressed in all patients with glioma and histological subtype astrocytoma. The gene expression profile is significantly associated with clinical manifestations. These results suggested that both the multigene expression patterns and individual central carbon metabolism–associated genes were potentially capable to predict the prognosis of patients with low-grade glioma.

Abstract Background Non-expressor of pathogenesis-related genes 1 (NPR1) regulates expression of pathogenesis-related (PR) genes by interacting with TGA family proteins during systemic acquired resistance (SAR). However, no TGA-like proteins or their interacting partners have been characterized in lily. Results In the present study, LhSorTGA2, a novel TGA-like protein, was identified as an interacting partner of LhSorNPR1 (an NPR-like protein) by bimolecular fluorescence complementation (BIFC) and yeast two-hybrid assay (Y2H). Subcellular localization of GFP-tagged proteins targeted LhSorTGA2 to the nucleus, whereas GFP-labeled LhSorNPR1 was observed both in the nucleus and at the cytomembrane. Sequence alignment revealed that LhSorTGA2 was featured with a basic leucine zipper (bZIP) domain and two glutamine rich acid domains (QI and QII). Further phylogenetic analysis showed that TGA family proteins can be grouped into three subclades, within which LhSorTGA2 was clustered into subclade I, together with AtTGA2/5/6. Expression of LhSorTGA2 was investigated in different tissues by qPCR, and the highest expression level was observed in stem. Besides, when treated with phytohormones (SA, MeJA, ETH and ABA) or fungal pathogen Botrytis elliptica, LhSorTGA2 expression was also induced at different time points post treatments. Conclusions Collectively, these results suggested that LhSorTGA2 was an interacting partner of LhSorNPR1, which might function in regulating expression of PR genes in lily during SAR.

Ginkgo biloba is an economically valuable tree, as a variety of flavonoid compounds are produced by the leaves of its seedlings. Although soil salinity is a serious threat to agricultural productivity worldwide, the effect of salt stress on G. biloba seedlings remains unclear. In this study, we found that under high NaCl concentrations (200 and 300 mmol/L), seedling growth was inhibited and the water content, chlorophyll, and peroxidase (POD) enzyme activity were significantly decreased in the leaves, whereas the soluble protein and proline levels increased significantly. However, at low NaCl concentrations (50 and 100 mmol/L), the seedlings grew normally because of the regulation of catalase (CAT) and POD enzyme activities. To elucidate the molecular mechanisms behind G. biloba salt tolerance, we examined the transcriptome of G. biloba seedlings treated with 100 mmol/L NaCl. Twelve differentially expressed genes (DEGs) were found to be involved in ion osmotic potential signal transduction and amplification, including two ABA signaling genes, five CDPK/CIPK genes, and five mitogen-activated protein kinase (MAPK) signaling genes. We also found that NAC transcription factors may be involved in the salt stress response; these included positive regulators (Gb_12203, Gb_27819, Gb_37720, and Gb_41540) and negative regulators (Gb_32549, Gb_35048, and Gb_37444). Importantly, treatment with 100 mmol/L NaCl can significantly improve flavonoid and flavonol glycoside biosynthesis. Simultaneously, the expression of flavonoid biosynthesis-related genes, including PAL (Gb_10949, Gb_21115) and FLS (Gb_00285, Gb_14024, and Gb_14029), was significantly upregulated. Based on these results, we reveal that G. biloba seedlings can tolerate low-level soil salinity stress through the regulation of different kinds of genes and transcriptome factors, especially flavonoid biosynthesis, which is improved to respond to environmental stress.

Plant zinc finger-homeodomain (ZHD) genes encode a family of transcription factors that have been demonstrated to play an important role in the regulation of plant growth and development. In this study, we identified a total of 13 ZHD genes (VvZHD) in the grape genome that were further classified into at least seven groups. Genome synteny analysis revealed that a number of VvZHD genes were present in the corresponding syntenic blocks of Arabidopsis, indicating that they arose before the divergence of these two species. Gene expression analysis showed that the identified VvZHD genes displayed distinct spatiotemporal expression patterns, and were differentially regulated under various stress conditions and hormone treatments, suggesting that the grape VvZHDs might be also involved in plant response to a variety of biotic and abiotic insults. Our work provides insightful information and knowledge about the ZHD genes in grape, which provides a framework for further characterization of their roles in regulation of stress tolerance as well as other aspects of grape productivity.

The exocyst is a conserved protein complex, and required for vesicles tethering, fusion and polarized exocytosis. Exo70A1, the exocyst subunit, is essential for assembly of the exocyst complex. To better understand potential roles of Exo70A1 in non-heading Chinese cabbage (Brassica campestris ssp. chinensis), we obtained the full-length cDNA of Exo70A1 gene, which consisted of 1917 bp and encoded a protein of 638 amino acids. BlastX showed BcExo70A1 shared 94.9% identity with Brassica oleracea var. acephala (AEI26267.1), and clustered into a same group with other homologues in B. oleracea var. acephala and Brassica napus. Subcellular localization analysis showed BcExo70A1 was localized to punctate structures in cytosol of onion epithelial cells. Results showed that BcExo70A1 was widely presented in stamens, young stems, petals, unpollinated pistils, roots and leaves of self compatible and incompatible plants. The transcripts of BcExo70A1 in non-heading Chinese cabbage declined during initial 1.5 h after incompatible pollination, while an opposite trend was presented after compatible pollination. Our study reveals that BcExo70A1 could play essential roles in plant growth and development, and is related to the rejection of self pollen in non-heading Chinese cabbage.

Yellow horn (Xanthoceras sorbifolium Bunge) is an endemic oil-rich shrub that has been widely cultivated in northern China for bioactive oil production. However, little is known regarding the molecular mechanisms that contribute to oil content in yellow horn. Herein, we measured the oil contents of high- and low-oil yellow horn embryo tissues at four developmental stages and investigated the global gene expression profiles through RNA-seq. The results found that at 40, 54, 68, and 81 days after anthesis, a total of 762, 664, 599, and 124 genes, respectively, were significantly differentially expressed between the high- and low-oil lines. Gene ontology (GO) enrichment analysis revealed some critical GO terms related to oil accumulation, including acyl-[acyl-carrier-protein] desaturase activity, pyruvate kinase activity, acetyl-CoA carboxylase activity, and seed oil body biogenesis. The identified differentially expressed genes also included several transcription factors, such as, AP2-EREBP family members, B3 domain proteins and C2C2-Dof proteins. Several genes involved in fatty acid (FA) biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism were also up-regulated in the high-oil line at different developmental stages. Our findings indicate that the higher oil accumulation in high-oil yellow horn could be mostly driven by increased FA biosynthesis and carbon supply, i.e. a source effect.

Isorhamnetin (IH) has been reported to have significant anti-inflammatory effects in various diseases, but its role and mechanism in AKI remain unclear. This study aimed to explore the potential role and mechanism of isorhamnetin in inhibiting macrophage related inflammation and improving AKI injury. We established an AKI mouse model by intraperitoneal injection of cisplatin in vivo, and constructed an inflammatory cell model by stimulating RAW264.7 cells with LPS. Creatinine and urea nitrogen were measured to evaluate the changes of renal function in AKI mice. The changes of renal pathological structure were observed by H&E staining. The inflammatory factor-related proteins and RNA expression levels were detected by Western blot and real time PCR. Isorhamnetin protected the kidney from cisplatin induced AKI and significantly inhibited the mRNA and protein levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) both in AKI kidney and LPS-stimulated RAW264.7 cells. Interestingly, the data also demonstrated that isorhamnetin significantly upregulated the expression of secretory leukocyte peptidase inhibitor (SLPI), an anti-inflammatory factor, in AKI kidney and LPS-stimulated macrophages, as well as inhibited the M1 macrophage and activated M2 macrophage in vitro. Blocking of SLPI by siRNA activated Mincle-associated inflammatory signaling in macrophages, and the inhibitory effect of isorhamnetin on inflammation was significantly attenuated. Isorhamnetin inhibits macrophage inflammation and protects kidney in AKI may be related to downregulating Mincle/Syk/NF-κB-maintained macrophage phenotype by activating SLPI. [ABSTRACT FROM AUTHOR]

During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Sonic Hedgehog (Shh) signaling promotes the cortical RGC lineage switch to generate cortical oligodendrocytes and OB interneurons. During this process, cortical RGCs generate intermediate progenitor cells that express critical gliogenesis genes Ascll, Egfr, and Olig2. The increased Ascll expression and appearance of Egfr+ and Olig2+ cortical progenitors are concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Furthermore, the transcriptional regulation of Olig2 and Egfr has not been explored. Here, we show that in cortical progenitor cells, multiple regu-latory programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between the mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells. [ABSTRACT FROM AUTHOR]

Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants. However, the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans (Glycine max). In this study, we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers. Molecular and genetic studies have characterized two antagonistic regulators, the positive activator GmMYBA3 and the negative repressor GmMYBR1, that modulate the gene expression of anthocyanin biosynthesis in soybean flowers. Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a, highlighting the complexity of anthocyanin regulation in different soybean organs. Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis-related genes, with GmF3050H identified as a crucial determinant of white flower color. This study provides a molecular mechanism underlying soybean flower color determination, paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is a highly heterogeneous and malignant gynecological cancer, thereby leading to poor clinical outcomes. The study aims to identify and characterize clinically relevant subtypes in OC and develop a diagnostic model that can precisely stratify OC patients, providing more diagnostic clues for OC patients to access focused therapeutic and preventative strategies. Methods: Gene expression datasets of OC were retrieved from TCGA and GEO databases. To evaluate immune cell infiltration, the ESTIMATE algorithm was applied. A univariate Cox analysis and the two-sided log-rank test were used to screen OC risk factors. We adopted the ConsensusClusterPlus algorithm to determine OC subtypes. Enrichment analysis based on KEGG and GO was performed to determine enriched pathways of signature genes for each subtype. The machine learning algorithm, support vector machine (SVM) was used to select the feature gene and develop a diagnostic model. A ROC curve was depicted to evaluate the model performance. Results: A total of 1,273 survival-related genes (SRGs) were firstly determined and used to clarify OC samples into different subtypes based on their different molecular pattern. SRGs were successfully stratified in OC patients into three robust subtypes, designated S-I (Immunoreactive and DNA Damage repair), S-II (Mixed), and S-III (Proliferative and Invasive). S-I had more favorable OS and DFS, whereas S-III had the worst prognosis and was enriched with OC patients at advanced stages. Meanwhile, comprehensive functional analysis highlighted differences in biological pathways: genes associated with immune function and DNA damage repair including CXCL9, CXCL10, CXCL11, APEX, APEX2, and RBX1 were enriched in S-I; S-II combined multiple gene signatures including genes associated with metabolism and transcription; and the gene signature of S-III was extensively involved in pathways reflecting malignancies, including many core kinases and transcription factors involved in cancer such as CDK6, ERBB2, JAK1, DAPK1, FOXO1, and RXRA. The SVM model showed superior diagnostic performance with AUC values of 0.922 and 0.901, respectively. Furthermore, a new dataset of the independent cohort could be automatically analyzed by this innovative pipeline and yield similar results. Conclusion: This study exploited an innovative approach to construct previously unexplored robust subtypes significantly related to different clinical and molecular features for OC and a diagnostic model using SVM to aid in clinical diagnosis and treatment. This investigation also illustrated the importance of targeting innate immune suppression together with DNA damage in OC, offering novel insights for further experimental exploration and clinical trial. [ABSTRACT FROM AUTHOR]

Severity of neurobehavioral deficits in children born from adverse pregnancies, such as maternal alcohol consumption and diabetes, does not always correlate with the adversity's duration and intensity. Therefore, biological signatures for accurate prediction of the severity of neurobehavioral deficits, and robust tools for reliable identification of such biomarkers, have an urgent clinical need. Here, we demonstrate that significant changes in the alternative splicing (AS) pattern of offspring lymphocyte RNA can function as accurate peripheral biomarkers for motor learning deficits in mouse models of prenatal alcohol exposure (PAE) and offspring of mother with diabetes (OMD). An aptly trained deep-learning model identified 29 AS events common to PAE and OMD as superior predictors of motor learning deficits than AS events specific to PAE or OMD. Shapley-value analysis, a game-theory algorithm, deciphered the trained deep-learning model's learnt associations between its input, AS events, and output, motor learning performance. Shapley values of the deep-learning model's input identified the relative contribution of the 29 common AS events to the motor learning deficit. Gene ontology and predictive structure-function analyses, using Alphafold2 algorithm, supported existing evidence on the critical roles of these molecules in early brain development and function. The direction of most AS events was opposite in PAE and OMD, potentially from differential expression of RNA binding proteins in PAE and OMD. Altogether, this study posits that AS of lymphocyte RNA is a rich resource, and deep-learning is an effective tool, for discovery of peripheral biomarkers of neurobehavioral deficits in children of diverse adverse pregnancies. [ABSTRACT FROM AUTHOR]

[Objectives] To observe the effects of Cigu Xiaozhi Formula on mfR-378a-3/> expression and Hh signaling pathway in TGF-ßl induced and activated 1X2 cells. [Methods] Cells were divided into control group, induction group, drug-containing serum group, miR-378a-3p inhibitor group, and miR inhibitor NC group. CCK-8 method was used to detect the cell viability of each group, and flow cytometry was used to detect the apoptosis rate of each group. RT-qPCR was used to detect the expression of miR-378a-3p in each group's cells, and RT-qPCR and Western blot were used to detect mRNA and protein expression of Shh, Glil, Gli2, Col-1, and a-SMA in each group's cells. [Results] Compared with the control group, the cell viability and expression of Shh, Glil, Gli2, Col-I, and a-SMA mRNA and protein in induction group increased (P <0.01), while the expression of miR-378a-3p decreased (P <0.01). Compared with the induction group, the cell viability and expression of Shh, GUI, GUI, Col-I, a-SMA mRNA and a-SMA and Gli2 protein decreased in drug-containing serum group (P<0.05), while cell apoptosis rate and zniR-378a-3p expression increased (P<0. 01). In miR-378a-3p inhibitor group, cell viability and the expression of Shh, GliA, Glil, Col-I, a-.S/17/l mRNA and Glil, Gli2, a-SMA protein increased (P <0.05, P <0. 01), while the apoptosis rate and miR-378a-3p expression decreased (P<0.05, P <0. 01). [Conclusions] Cigu Xiaozhi Formula containing serum can upregulate zmR-378<2-3p expression and downregulate the expression of Gli2 and a-SMA in TGF-ßl induced LX2 cells, thereby inhibiting the activation of LX2 cells and exerting the effects of anti liver fibrosis. [ABSTRACT FROM AUTHOR]

Extended-spectrum beta-lactamase-producing Gram-negative bacteria are common in the community and hospitals. To monitor ESBLs mediated by the CTX-M genotype, we collected clinical ESBL pathogenic strains from a hospital in central China and observed a strain of Escherichia coli, namely Ec15103 carrying blaCTX-M-14, blaCTX-M-64 and blaTEM-1, isolated from the blood of a 7-day-old infant in 2015. Strain Ec15103 contains two drug resistance plasmids: pEc15103A, an IncFI-type plasmid that cannot be conjugatively transferred and carries the drug resistance genes blaTEM-1, aacC2, aadA5, sull, mph(A), sul2, strAB, and tetA(A); and pEc15103B, an IncK2/Z-type plasmid that carries the conjugation transfer gene and blaCTX-M-14. In addition, blaCTX-M-64 is located on the chromosome of Ec15103, and it is the first report of pathogen with blaCTX-M-64 located on its chromosome (the search terms used "blaCTX-M-64" and "chromosome"). blaCTX-M-14 and blaCTX-M-64 are carried by ISEcpl-mediated transposon Tn6503a and Tn6502, respectively. The conjugation transfer ability of pEc15103B was significantly inhibited by zidovudine (AZT) and linoleic acid (LA) and that expression of blaCTX-M-14, blaCTX-M-64 and blaTEM-1 at the mRNA level did not change based on the concentration of cefotaxime or ampicillin. Co-occurrence of blaCTX-M-14 and blaCTX-M-64 in a single isolate will enhance the drug resistance of bacteria, and the presence of blaCTX-M-64 in the chromosome may make the resistance more maintain. This fact will facilitate its dissemination and persistence under different antimicrobial selection pressures. It is essential to prevent these strains from further spreading in a hospital environment. [ABSTRACT FROM AUTHOR]

Aim: Sepsis is an extremely complex, threatening and difficult-to-treat disease, which can occur at any age and under any underlying disease. RNF20 regulate NF-kappaB (NF-κB) signaling pathway and the transcription of inflammatory factors of target genes. Therefore, it is of great significance to study the function of RNF20 in the clinical treatment of sepsis and its underlying mechanisms. Methods: C57BL/6 mice were subjected to cecal ligation and puncture (CLP) surgery. THP-1 cells were induced with Lipopolysaccharide for 4 h. Results: RNF20 gene, mRNA expression and protein expression were reduced in patients with sepsis and mice with sepsis. Based on RNF20 deletion (RNF20-/-) mice, these were found to be increased inflammation reactions in RNF20-/- mice. However, the RNF20 human protein reduced inflammation reactions in mice with sepsis. In vitro model of sepsis, over-expression of RNF20 inhibited inflammation reactions by inducing Vitamin D Receptor (VDR), while down-regulation of RNF20 promoted inflammation reactions through the suppression of VDR. RNF20 protein was interlinked with VDR protein, and VDR protein was also interlinked with NLRP3. Furthermore, VDR promoted NLRP3 ubiquitination and reduced NLRP3 function in vitro model of sepsis. Conclusion: These studies demonstrate that RNF20 suppressed inflammation reactions in models with sepsis through NLRP3 inflammasome and NLRP3 ubiquitination by activating VDR. [ABSTRACT FROM AUTHOR]

World-wide, rice (Oryza sativa L.) is an important food source, and its production is often adversely affected by salinity. Therefore, to ensure stable rice yields for global food security, it is necessary to understand the salt tolerance mechanism of rice. The present study focused on the expression pattern of the rice mismatch repair gene post-meiotic segregation 1 (OsPMS1), studied the physiological properties and performed transcriptome analysis of ospms1 mutant seedlings in response to salt stress. Under normal conditions, the wild-type and ospms1 mutant seedlings showed no significant differences in growth and physiological indexes. However, after exposure to salt stress, compared with wild-type seedlings, the ospms1 mutant seedlings exhibited increased relative water content, relative chlorophyll content, superoxide dismutase (SOD) activity, K+ and abscisic acid (ABA) content, and decreased malondialdehyde (MDA) content, Na+ content, and Na+/K+ ratio, as well as decreased superoxide anion (O2−) and hydrogen peroxide (H2O2) accumulation. Gene ontology (GO) analysis of the differentially expressed genes (DEGs) of ospms1 mutant seedlings treated with 0 mM and 150 mM NaCl showed significant enrichment in biological and cytological processes, such as peroxidase activity and ribosomes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis showed that the DEGs specifically enriched ascorbate and aldarate metabolism, flavone and flavonol biosynthesis, and glutathione metabolism pathways. Further quantitative real-time reverse transcription-PCR (qRT-PCR) analysis revealed significant changes in the transcription levels of genes related to abscisic acid signaling (OsbZIP23, OsSAPK6, OsNCED4, OsbZIP66), reactive oxygen scavenging (OsTZF1, OsDHAR1, SIT1), ion transport (OsHAK5), and osmoregulation (OsLEA3-2). Thus, the study's findings suggest that the ospms1 mutant tolerates salt stress at the seedling stage by inhibiting the accumulation of reactive oxygen species, maintaining Na+ and K+ homeostasis, and promoting ABA biosynthesis. [ABSTRACT FROM AUTHOR]

Recently, a novel poplar mosaic disease caused by bean common mosaic virus (BCMV) was investigated in Populus alba var. pyramidalis in China. Symptom characteristics, physiological performance of the host, histopathology, genome sequences and vectors, and gene regulation at the transcriptional and posttranscriptional levels were analyzed and RT-qPCR (quantitative reverse transcription PCR) validation of expression was performed in our experiments. In this work, the mechanisms by which the BCMV pathogen impacts physiological performance and the molecular mechanisms of the poplar response to viral infection were reported. The results showed that BCMV infection decreased the chlorophyll content, inhibited the net photosynthesis rate (Pn) and stomatal conductance (Gs), and significantly changed chlorophyll fluorescence parameters in diseased leaves. Transcriptome analysis revealed that the expression of the majority of DEGs (differentially expressed genes) involved in the flavonoid biosynthesis pathway was promoted, but the expression of all or almost all DEGs associated with photosynthesis-antenna proteins and the photosynthesis pathway was inhibited in poplar leaves, suggesting that BCMV infection increased the accumulation of flavonoids but decreased photosynthesis in hosts. Gene set enrichment analysis (GSEA) illustrated that viral infection promoted the expression of genes involved in the defense response or plant-pathogen interaction. MicroRNA-seq analysis illustrated that 10 miRNA families were upregulated while 6 families were downregulated in diseased poplar leaves; moreover, miR156, the largest family with the most miRNA members and target genes, was only differentially upregulated in longperiod disease (LD) poplar leaves. Integrated transcriptome and miRNA-seq analyses revealed 29 and 145 candidate miRNA-target gene pairs; however, only 17 and 76 pairs, accounting for 2.2% and 3.2% of all DEGs, were authentically negatively regulated in short-period disease (SD) and LD leaves, respectively. Interestingly, 4 miR156/SPL (squamosa promoter-binding-like protein) miRNA -target gene pairs were identified in LD leaves: the miR156 molecules were upregulated, but SPL genes were downregulated. In conclusion, BCMV infection significantly changed transcriptional and posttranscriptional gene expression in poplar leaves, inhibited photosynthesis, increased the accumulation of flavonoids, induced systematic mosaic symptoms, and decreased physiological performance in diseased poplar leaves. This study elucidated the fine-tuned regulation of poplar gene expression by BCMV; moreover, the results also suggested that miR156/SPL modules played important roles in the virus response and development of viral systematic symptoms in plant virus disease. [ABSTRACT FROM AUTHOR]

Objectives: Gestational hypertension (GH), the most common type of hypertensive disorders in pregnancy, often occurs in women during pregnancy. The purpose of this study was to investigate the expression and clinical significance of lncRNA NORAD in gestational hypertension, and to discuss the possibility of lncRNA NORAD as a diagnostic marker of gestational hypertension. Material and methods: A total of 219 participants were involved in the study. Basic clinical information of all participants was collected, and the expression of NORAD in serum was detected by RT-qPCR. ROC curves were drawn to evaluate the diagnostic value of NORAD expression for gestational hypertension. Multiple linear regression analysis was done to explore the relationship between NORAD and clinical variables. Logistic regression analysis was conducted to analyze the independent influence of different variables on the development of gestational hypertension into preeclampsia. Results: The expression level of NORAD in gestational hypertension was higher than that of healthy individuals, and the expression level of NORAD in preeclampsia was higher than that of gestational hypertension and healthy individuals. The ROC curve suggested that the expression of NORAD has a higher diagnostic value for gestational hypertension. Multiple linear regression analysis showed that systolic blood pressure (SBP) and diastolic blood pressure (DBP) were correlated with the expression of NORAD. SBP, DBP and NORAD were all factors that affect the development of gestational hypertension to preeclampsia, which were known by logistic regression analysis. Conclusions: LncRNA NORAD may be used as a biomarker for gestational hypertension diagnosis and can influence its progression into preeclampsia. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous crosstalk between tumor cells and other cells in their microenvironment means a notable difference in clinical outcomes of head and neck squamous cell carcinoma (HNSCC). CD8+ T cells and macrophages are effector factors of the immune system, which have direct killing and phagocytosis effects on tumor cells. How the evolution of their role in the tumor microenvironment influences patients clinically remains a mystery. This study aims to investigate the complex communication networks in the HNSCC tumor immune microenvironment, elucidate the interactions between immune cells and tumors, and establish prognostic risk model. Methods: 20 HNSCC samples single-cell rna sequencing (scRNA-seq) data and bulk rna-seq data were derived from public databases. The "cellchat" R package was used to identify cell-to-cell communication networks and prognostic related genes, and then cell-cell communication (ccc) molecular subtypes were constructed by unsupervised clustering. Kaplan-Meier(K-M) survival analysis, clinical characteristics analysis, immune microenvironment analysis, immune cell infiltration analysis and CD8+T cell differentiation correlation analysis were performed. Finally, the ccc gene signature including APP, ALCAM, IL6, IL10 and CD6 was constructed based on univariate Cox analysis and multivariate Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model in the train group and the validation group, respectively. Results: With CD8+T cells from naive to exhaustion state, significantly decreased expression of protective factor (CD6 gene) is associated with poorer prognosis in patients with HNSCC. The role of macrophages in the tumor microenvironment has been identified as tumor-associated macrophage (TAM), which can promote tumor proliferation and help tumor cells provide more nutrients and channels to facilitate tumor cell invasion and metastasis. In addition, based on the strength of all ccc in the tumor microenvironment, we identified five prognostic ccc gene signatures (cccgs), which were identified as independent prognostic factors by univariate and multivariate analysis. The predictive power of cccgs was well demonstrated in different clinical groups in train and test cohorts. Conclusion: Our study highlights the propensity for crosstalk between tumors and other cells and developed a novel signature on the basis of a strong association gene for cell communication that has a powerful ability to predict prognosis and immunotherapy response in patients with HNSCC. This may provide some guidance for developing diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) has become a common cause of cancer-related death. Many studies have shown that the basement membrane (BM) is associated with the development of cancer. However, BM-related gene expression and its relationship to LUAD prognosis remains unclear. Methods: BM-related genes from previous studies were used. Clinical and mRNA expression information were obtained from TCGA database. Cox, minimum absolute contraction, and selection operator regression were applied to analyze the selected genes affecting LUAD prognosis. A prognostic-risk model was then established. Furthermore, this study applied Kaplan-Meier analysis to assess the outcomes of high- and low-risk groups, then explored their differences in drug sensitivity. The DSigDB database was used to screen for therapeutic smallmolecule drugs. Results: Fourteen prognostic models based on BM-related genes were successfully constructed and validated in patients with LUAD. We also found that independence was a prognostic factor in all 14 BM-based models. Functional analysis showed that the enrichment of BM-related genes mainly originated from signaling pathways related to cancer. The BM-based model also suggested that immune cell infiltration is associated with checkpoints. The low-risk patients may benefit from cyclopamine and docetaxel treatments. Conclusion: This study identified a reliable biomarker to predict survival in patients with LUAD and offered new insights into the function of BM-related genes in LUAD. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer's disease (AD) through gene expression changes. Methods: The GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aβ1-42 on the expression profile of representative genes in vitro. Results: Based on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 upregulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aβ1-42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aβ1-42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased. Discussion: The establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Mammalian testis exhibits remarkably high transcriptome complexity, and spermatogenesis undergoes two periods of transcriptional cessation. These make the RNA-binding proteins (RBPs) the utmost importance during male germ cell development. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of RBPs implicated in many steps of RNA processing; however, their roles in spermatogenesis are largely unknown. Here, we investigated the expression pattern of 12 hnRNP family members in mouse testes and found that most detected members are highly expressed in the testis. Furthermore, we found that most of the detected hnRNP proteins (hnRNPD, hnRNPK, hnRNPQ, hnRNPU, and hnRNPUL1) display the highest signals in the nuclei of pachytene spermatocytes, round spermatids, and Sertoli cells, whereas hnRNPE1 exclusively concentrates in the manchette of elongating spermatids. The expression of these hnRNP proteins showed both similarities and specificity, suggesting their diverse roles in spermatogenesis. [ABSTRACT FROM AUTHOR]

Context: Pileostegia tomentella hand. Mazz (saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. tumour angiogenesis mediated by exosomes-derived miRNa exhibits the vital regulation of endothelial cell function in metastasis of CRC. Objective: to investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells. Materials and methods: HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/ml) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. co-culture experiments for human umbilical vein endothelial cells (HUVECS) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNas in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNa into HUVECs. Results: HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 AND VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in exo-tcPt. Rescue assays showed that high expression of miR-375-3p in hUVecs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects. Discussion and conclusion: TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of Pileostegia tomentella in CRC. [ABSTRACT FROM AUTHOR]

Background: Lactate, a byproduct of glucose metabolism, is primarily utilized for gluconeogenesis and numerous cellular and organismal life processes. Interestingly, many studies have demonstrated a correlation between lactate metabolism and tumor development. However, the relationship between long non-coding RNAs (lncRNAs) and lactate metabolism in papillary thyroid cancer (PTC) remains to be explored. Methods: Lactate metabolism-related lncRNAs (LRLs) were obtained by differential expression and correlation analyses, and the risk model was further constructed by least absolute shrinkage and selection operator analysis (Lasso) and Cox analysis. Clinical, immune, tumor mutation, and enrichment analyses were performed based on the risk model. The expression level of six LRLs was tested using RT-PCR. Results: This study found several lncRNAs linked to lactate metabolism in both The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Using Cox regression analysis, 303 lactate LRLs were found to be substantially associated with prognosis. Lasso was done on the TCGA cohort. Six LRLs were identified as independent predictive indicators for the development of a PTC prognostic risk model. The cohort was separated into two groups based on the median risk score (0.39717 -0.39771). Subsequently, Kaplan-Meier survival analysis and multivariate Cox regression analysis revealed that the high-risk group had a lower survival probability and that the risk score was an independent predictive factor of prognosis. In addition, a nomogram that can easily predict the 1-, 3-, and 5-year survival rates of PTC patients was established. Furthermore, the association between PTC prognostic factors and tumor microenvironment (TME), immune escape, as well as tumor somatic mutation status was investigated in high- and low-risk groups. Lastly, gene expression analysis was used to confirm the differential expression levels of the six LRLs. Conclusion: In conclusion, we have constructed a prognostic model that can predict the prognosis, mutation status, and TME of PTC patients. The model may have great clinical significance in the comprehensive evaluation of PTC patients. [ABSTRACT FROM AUTHOR]