Antifungal Activity and Mechanism of Xenocoumacin 1, a Natural Product from Xenorhabdus nematophila against Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum (Lib.) de Bary, a polyphagous necrotrophic fungal pathogen, has brought about significant losses in agriculture and floriculture. Until now, the most common method for controlling S. sclerotiorum has been the application of fungicides. Xenocoumacin 1 (Xcn1) is a potential biopesticide having versatile antimicrobial activities, generated by Xenorhabdus nematophila. This study was intended to isolate Xcn1 from X. nematophila YL001 and clarify its efficacies for S. sclerotiorum control. Xcn1 demonstrated a wider antifungal spectrum against 10 plant-pathogenic fungi. It also exhibited a strong inhibitory effect on the mycelial growth of S. sclerotiorum with an EC50 value of 3.00 µg/mL. Pot experiments indicated that Xcn1 effectively inhibited disease extension on oilseed rape and broad bean plants caused by S. sclerotiorum. Morphological and ultrastructural observations revealed that the hyphae of S. sclerotiorum became twisted, shriveled, and deformed at the growing points after treatment with Xcn1 at 3.00 µg/mL and that the subcellular fractions also became abnormal concurrently, especially the mitochondrial structure. Moreover, Xcn1 also increased cell membrane permeability and decreased the content of exopolysaccharide as well as suppressing the activities of polygalacturonase and cellulase of S. sclerotiorum, but exerted no effects on oxalic acid production. This study demonstrated that Xcn1 has great potential to be developed as a new biopesticide for the control of S. sclerotiorum.

Investigating the neuroprotective potential of rAAV2-PCBP1-EGFP gene therapy against a 6-OHDA-induced model of Parkinson's disease.

OBJECTIVES: Previous studies have suggested a potential link between poly(rC)-binding protein 1 (PCBP1) and neurodegenerative diseases, including Parkinson's disease (PD). However, the precise role of PCBP1 in the pathogenesis of PD remains unclear. Therefore, the main objective of this study was to investigate the neuroprotective effects of PCBP1 in a PD model. METHODS: To evaluate the neuroprotective potential of PCBP1, we conducted cell count assays and observed the expression of heat shock protein 70 (HSP70) in SH-SY5Y cells exposed to 6-OHDA-induced neurotoxicity. Additionally, we utilized recombinant adeno-associated virus (rAAV2) vectors encoding PCBP1 or EGFP, which were injected into the rat striatum. After 2 weeks of vector or saline injection, 6-OHDA was administered to the rat striatum. Behavioral assessments using the open field test (OFT) were performed weekly for 7 weeks. At the seventh week after 6-OHDA injection, immunohistochemistry and protein expression analyses were conducted in the three groups. RESULTS: The results indicated that PCBP1 treatment significantly reduced the proliferation of 6-OHDA-induced SH-SY5Y cells. Additionally, in surviving cells, overexpression of PCBP1 enhanced the expression of HSP70. Similarly, rAAV2 vectors effectively delivered PCBP1 into the brain, resulting in sustained expression of rAAV2-PCBP1-EGFP. In the OFT, PCBP1 exhibited significant improvements in behavioral abnormalities and reduced anxiety in the PD model rats (p < .01). Moreover, PCBP1 effectively prevented the decrease of tyrosine hydroxylase and HSP70 expression in the lesioned side induced by 6-OHDA (p < .01). Consistent with expectations, PCBP1 efficiently protected against cell death caused by 6-OHDA (p < .01). CONCLUSIONS: In conclusion, our findings provide compelling evidence for the beneficial effects of PCBP1 in the PD model, suggesting that PCBP1 could be a potential therapeutic target for PD.

Efficacy and Safety of Triptorelin 3-Month Formulation in Chinese Children with Central Precocious Puberty: A Phase 3, Open-Label, Single-Arm Study.

INTRODUCTION: Triptorelin is available as 1- and 3-month prolonged-release (PR) formulations; at the time of the study, only the former was approved for central precocious puberty (CPP) in China. This study assessed the efficacy and safety of the triptorelin 3-month PR formulation in Chinese children with CPP. METHODS: In this 12-month, prospective, open-label, multicentre, single-arm study (NCT04736602), Chinese children (mean age [standard deviation (SD)], 7.6 ± 0.8 years) with CPP received triptorelin pamoate 15 mg on day 1 and at months 3, 6 and 9. The primary endpoint was the proportion with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 3 IU/L after gonadotropin-releasing hormone [GnRH] stimulation) at month 3. Secondary endpoints included changes from baseline in hormone levels and clinical parameters, as well as safety assessments. RESULTS: Overall, 32 children were enrolled, including three boys. LH suppression to prepubertal levels (≤ 3 IU/L) after GnRH stimulation was observed in 100%, 93.5% and 93.5% of participants at months 3, 6 and 12, respectively. Basal and peak LH and follicle-stimulating hormone levels were substantially suppressed at months 3, 6 and 12, and most participants showed sex hormone suppression. At months 6 and 12 respectively 92.9% and 89.3% of girls had stable breast development, and all boys had stable genital development. There was a decrease in mean growth velocity from baseline (8.96 cm/year) to months 3, 6 and 12 (8.07, 5.24 and 6.94 cm/year, respectively). The mean difference between bone and chronological age decreased from baseline (2.85 years) to month 12 (2.39 years). In girls, uterine length was stable or reduced at month 12; in boys, testicular volume was reduced. Triptorelin was well tolerated. CONCLUSION: The triptorelin 3-month PR formulation demonstrated similar efficacy to that previously reported in non-Chinese patients with CPP and had an acceptable safety profile. This supports triptorelin 3-month PR as a viable option for Chinese children with CPP.

Central precocious puberty (CPP) occurs when the reproductive organs and secondary sexual characteristics develop too early in children (before 8 years old in girls or 9 years old in boys). It can cause significant psychological harm and may lead to health problems later in life. Triptorelin is a type of treatment designed to suppress the hormonal activity responsible for CPP and therefore slow down early pubertal development. Triptorelin can be given as an injection into muscle every month or every 3 months; the 3-monthly formulation is commonly used in many countries but at the time of this study it was not licensed for patients with CPP in China. Our trial assessed the effect of triptorelin treatment every 3 months for 1 year in 32 Chinese children with CPP. For all patients who had measurements available, 3-monthly triptorelin suppressed luteinizing hormone­a key hormone involved in CPP­to below typical prepubertal levels. Other hormones involved in puberty were also suppressed. Children experienced a slowing down of the development of secondary sexual characteristics (breasts, genitals and pubic hair), and stabilization or reduction in the size of internal sexual organs (uterine length in girls and testicular volume in boys). Their height also increased less rapidly than previously. There were no concerning side effects of triptorelin treatment, and the safety profile matched that seen in other countries where triptorelin is widely used for CPP. Overall, our study findings suggest that the 3-monthly triptorelin formulation may be a good option for Chinese children with CPP.

Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer.

BACKGROUND: Cancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung. METHODS: Exome sequencing was performed on germline DNA from 55 Singapore patients (52 [95%] never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case-control association analyses were performed. RESULTS: Altogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such as BRCA2, TP53, and RAD51D; but also lesser known cancer genes EXT2, WWOX, GATA2, and GPC3. Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations. CONCLUSIONS: We have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers.

A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC.

Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC. Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression. The primary end point was the objective response rate, and the secondary end points included progression-free survival, overall survival, and safety of ICI after EGFR TKI. Results: Recruitment ceased owing to futility after 31 of 184 planned patients were treated. A total of 15 patients received N and 16 received NI combination. There were 16 patients (51.6%) who had programmed death-ligand (PDL1) 1 greater than or equal to 1%, and 15 (45.2%) harbored EGFR T790M. Five patients derived clinical benefits from ICI with one objective response (objective response rate 3.2%), and median progression-free survival was 1.22 months (95% confidence interval: 1.15-1.35) for the overall cohort. None of the four patients who crossed over achieved salvage response by NI. PDL1 and tumor mutational burden (TMB) were not able to predict ICI response. Rates of all grade immune-related adverse events were similar (80% versus 75%), with only two grade 3 events. Conclusions: Immune checkpoint inhibition is ineffective in EGFR TKI-resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients.

Co-overexpression of AtSAT1 and EcPAPR improves seed nutritional value in maize.

Maize seeds synthesize insufficient levels of the essential amino acid methionine (Met) to support animal and livestock growth. Serine acetyltransferase1 (SAT1) and 3'-phosphoadenosine-5'-phosphosulfate reductase (PAPR) are key control points for sulfur assimilation into Cys and Met biosynthesis. Two high-MET maize lines pRbcS:AtSAT1 and pRbcS:EcPAPR were obtained through metabolic engineering recently, and their total Met was increased by 1.4- and 1.57-fold, respectively, compared to the wild type. The highest Met maize line, pRbcS:AtSAT1-pRbcS:EcPAPR, was created by stacking the two transgenes, causing total Met to increase 2.24-fold. However, the pRbcS:AtSAT1-pRbcS:EcPAPR plants displayed progressively severe defects in plant growth, including early senescence, stunting, and dwarfing, indicating that excessive sulfur assimilation has an adverse effect on plant development. To explore the mechanism of correlation between Met biosynthesis in maize leaves and storage proteins in developing endosperm, the transcriptomes of the sixth leaf at stage V9 and 18 DAP endosperm of pRbcS:AtSAT1, pRbcS:AtSAT1-pRbcS:EcPAPR, and the null segregants were quantified and analyzed. In pRbcS:AtSAT1-pRbcS:EcPAPR, 3274 genes in leaves (1505 up- and 1769 downregulated) and 679 genes in the endosperm (327 up- and 352 downregulated) were differentially expressed. Gene ontology (GO) and KEGG (Kyoto encyclopedia of genes and genomes) analyses revealed that many genes were associated with Met homeostasis, including transcription factors and genes involved in cysteine and Met metabolism, glutathione metabolism, plant hormone signal transduction, and oxidation-reduction. The data from gene network analysis demonstrated that two genes, serine/threonine-protein kinase (CCR3) and heat shock 70 kDa protein (HSP), were localized in the core of the leaves and endosperm regulation networks, respectively. The results of this study provide insights into the diverse mechanisms that underlie the ideal establishment of enhanced Met levels in maize seeds.

Potential Biochemical Pesticide-Synthesis of Neofuranocoumarin and Inhibition the Proliferation of Spodoptera frugiperda Cells through Activating the Mitochondrial Pathway.

Furanocoumarins, the secondary metabolites of plants, are considered to be natural insecticides and fungicides because they prevent the invasion of plant pathogenic microorganisms and the predation of herbivorous insects. In this study, novel 2-arylfuranocoumarin derivatives were designed to synthesize by condensation, esterification, bromination, and Wittig reaction. The results showed an excellent photosensitive activity of 2-thiophenylfuranocoumarin (I34). Cell Counting Kit-8 detected that I34 could inhibit the proliferation of Spodoptera frugiperda (Sf9) cells in a time- and concentration-dependent manner under ultraviolet A (UV-A) light for 3 min. The inverted microscope revealed that cells treated with I34 swelled, the membrane was ruptured, and apoptotic bodies appeared. The flow cytometry detected that I34 could induce apoptosis of Sf9 cells, increase the level of intracellular reactive oxygen species (ROS), decrease the mitochondrial membrane potential, and block cell cycle arrest in the G2/M phase. Transmission electron microscopy detected cell mitochondrial cristae damage, matrix degradation, and mitochondrial vacuolation. Further enzyme activity detection revealed that the enzyme activities of apoptosis-related proteins caspase-3 and caspase-9 increased significantly (p < 0.05). Finally, Western blotting analysis detected that the phosphorylation level of Akt and Bad and the expression of the apoptosis inhibitor protein Bcl-XL were inhibited, cleaved-PARP and P53 were increased, and cytochrome C was released from the mitochondria into the cytoplasm. Moreover, under UV-A irradiation, I34 promoted the increase in ROS in Sf9 cells, activated the mitochondrial apoptotic signal transduction pathway, and finally, inhibited cell proliferation. Thus, novel furanocoumarins exhibit a potential application prospect as a biochemical pesticide.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia

SUMMARY OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities.

PURPOSE: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFR T790M-negative resistance. EXPERIMENTAL DESIGN: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M+) and -negative (T790M-) disease. RESULTS: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M- tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M- tumors. Almost half of resistant tumors were further classified as immunehot, with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M- and T790M+ disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients. CONCLUSIONS: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.

Comparison of Antioxidant and Antibacterial Activities of Camellia Oil From Hainan With Camellia Oil From Guangxi, Olive Oil, and Peanut Oil.

Background/Aim: Camellia oil from Hainan (SY) is a unique vegetable oil in Hainan, China, due to the geographical environment and oil extraction only through simple physical treatments. To compare SY with camellia oil from Guangxi (SC), olive oil (GL), and peanut oil (HS), this study analyzed the antioxidant and antibacterial activity of four vegetable oils. Methods: Using Gallic acid, BHT as the control, Saccharomyces cerevisiae as the model organism, the antioxidant activities of vegetable oils were measured in vitro and in vivo, and the antibacterial activity was measured with the minimum inhibitory concentration (MIC) method. Results: The major contents of SY, SC, and HS were oleic Acid; the major content of GL was squalene. The highest total flavonoids content of SY was 39.50 ± 0.41 mg RE/g DW; and the highest total phenolic content of SC was 47.05 ± 0.72 mg GAE/g DW. SY exhibited the strongest scavenging activity of hydroxyl radical (HO·) and superoxide anions ( O 2 - · ), the IC50 value were 2.06 mg/mL, 0.62 mg/mL, respectively; and SC showed the strongest DPPH· and ABTS· scavenging activity and the reducing abilities. SY showed excellent effect on survival rate, protection rate, flavonoids uptake of S. cerevisiae cells, decreased MDA content and ROS level, inhibited CAT, POD, and GR enzyme activity. The absorption of SC total phenols was the highest by cells. The activity showed GL had a broad-spectrum antibacterial activity. Conclusion: Thus, SY shows potential antioxidant activity and provides an important reference value for people to choose edible vegetable oils.

Synthesis and Photoactivated Toxicity of 2-Thiophenylfuranocoumarin Induce Midgut Damage and Apoptosis in Aedes aegypti Larvae.

Furanocoumarins are photoactive compounds derived from secondary plant metabolites. They possess many bioactivities, including antioxidative, anticancer, insecticidal, and bactericidal activities. Here, we designed a new scheme for synthesizing 2-arylfuranocoumarin derivatives by condensation, esterification, bromination, and Wittig reaction. We found that 2-thiophenylfuranocoumarin (Iy) had excellent photosensitive activity. Three Iy concentrations (LC25, LC50, and LC75) were used to treat the fourth instar larvae of Aedes aegypti (A. aegypti). The photoactivated toxicity, sublethal dose, mitochondrial dysfunction, oxidative stress level, intestinal barrier dysfunction, and apoptosis were studied. The results showed that Iy induced reactive oxygen species (ROS) production in midgut cells under ultraviolet light. Ultrastructural analysis demonstrated that mitochondria were damaged, and the activities of related enzymes were inhibited. Ultimately, Iy exposure led to excessive ROS production followed by the inhibition of antioxidant enzymes, including SOD, CAT, GPx, and GR, which diminished ROS elimination and escalated oxidative stress in midgut cells, aggravating the degree of oxidative damage in these cells. Histopathological changes were observed in the midgut, which led to intestinal barrier dysfunction. When the elimination of ROS was blocked and it accumulated in cells, apoptosis-related genes, including AeDronc, AeCaspase7, and AeCaspase8, were induced and activated. In addition, Iy affected the growth and development of A. aegypti at sublethal concentrations, and there was an obvious post-lethal effect. Thus, we found that Iy caused midgut damage and apoptosis in A. aegypti larvae under ultraviolet light, which preliminarily revealed the mode of action of Iy in A. aegypti.

Endoscopic mask innovation and protective measures changes during the coronavirus disease-2019 pandemic: Experience from a Chinese hepato-biliary-pancreatic unit.

Endoscopy is widely used as a clinical diagnosis and treatment method for certain hepatobiliary and pancreatic diseases. However, due to the distinctive epidemiological characteristics of severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease-2019 (COVID-19), healthcare providers are exposed to the patient's respiratory and gastrointestinal fluids, rendering endoscopy a high risk for transmitting a nosocomial infection. This article introduces preventive measures for endoscopic treatment enacted in our medical center during COVID-19, including the adjustment of indications, the application of endoscope protective equipment, the design and application of endoscopic masks and splash-proof films, and novel recommendations for bedside endoscope pre-sterilization.

Genomic landscape of lung adenocarcinoma in East Asians.

Lung cancer is the world's leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts.

Oxidative Stress and Apoptosis of Gaeumannomyces graminis (Get) Induced by Carabrone.

Carabrone is isolated from Carpesium macrocephalum Franch. et Sav, which has good fungicidal activity, especially for Gaeumannomyces graminis (Get). According to previous studies, we speculated that carabrone targets the mitochondrial enzyme complex III of Get. To elucidate the mode of action, we used carabrone to induce oxidative stress and apoptosis in Get. Incubation with carabrone reduced the burst of reactive oxygen species (ROS) and mitochondrial membrane potential, as well as phosphatidylserine release. Carabrone caused ROS accumulation in mycelia by inhibiting the activity of antioxidase enzymes, among which inhibition of glutathione reductase (GR) activity was most obvious. The catalytic center of GR consists of l-cysteine residues that react with the α-methylene-γ-butyrolactone active site of carabrone. Additionally, a positive TUNEL reaction led to diffusion of the DNA electrophoresis band and upregulation of Ggmet1 and Ggmet2. We propose that carabrone inhibits antioxidant enzymes and promotes ROS overproduction, which causes membrane hyperpermeability, release of apoptotic factors, activation of the mitochondria-mediated apoptosis pathway, and fungal cell apoptosis.

High Expression of ABRACL Is Associated with Tumorigenesis and Affects Clinical Outcome in Gastric Cancer.

BACKGROUND: The ABRA C-terminal like (ABRACL) protein belongs to a novel family of low-molecular weight proteins that increase actin dynamics and cell motility. It is involved in various diseases including cancer; however, its role in gastric cancer is unclear. In this study, the expression of ABRACL in gastric cancer and its relationships with patients' clinicopathological features and survival are examined. METHODS: Sample expression profiles were downloaded from the Gene Expression Omnibus database and the Cancer Genome Atlas. ABRACL expression at the protein level in normal gastric and gastric cancer tissues was compared by using immunohistochemistry staining data provided by the Human Protein Atlas. Correlations between ABRACL expression and clinicopathological features are analyzed by chi-square tests. Patient survival was evaluated by Kaplan-Meier analysis. RESULTS: ABRACL expression is upregulated in gastric cancer tissues than in normal tissues. High ABRACL levels indicated a poor prognosis. ABRACL expression (low ABRACL, n = 96; high ABRACL, n = 96) in gastric cancer tissues (primary data from GSE15459) is significantly correlated with poor overall survival (χ2 = 4.078, p = 0.043; log-rank test). ABRACL protein levels (low ABRACL, n = 172, high ABRACL, n = 171) in gastric cancer tissues (primary data from www.kmplot.com ) are significantly correlated with poor overall survival (χ2 = 4.305, p = 0.038, log-rank test). CONCLUSIONS: Our results indicate that ABRACL is highly expressed in gastric cancer and is a potential prognostic marker and therapeutic target for this disease.

High expression of density-regulated re-initiation and release factor drives tumourigenesis and affects clinical outcome.

Previously, certain experiments have suggested that density-regulated re-initiation and release factor (DENR) could serve important roles in cancer, however, to the best of our knowledge, a comprehensive analysis of DENR and its association with cancer patient survival is lacking. The aim of the current study was to investigate the expression of DENR in multiple tumour types and to evaluate the effects of DENR on survival in malignancies. Sample expression profiles were downloaded from the Gene Expression Omnibus database. Association between DENR expression and clinicopathological features was analysed by Chi-square tests. The effects of DENR on survival were evaluated by Kaplan-Meier analysis. The results of the current study demonstrate that DENR expression was upregulated in nine cancer types. High DENR expression indicated poor prognosis of patients. The results of the present study demonstrated that DENR is highly expressed in multiple tumour types and may be used as a potential prognostic marker and therapeutic target.

Dynamic Analysis of Nucleosides and Carbohydrates during Developmental Stages of Cordyceps militaris in Silkworm (Bombyxmori).

Background: Cultured Cordyceps militaris is very popular. Objective: To gain dynamic insight into activity markers in fruiting body of Cordyceps militaris (C. militaris) in Bombyxmori (B. mori), also named silkworm. Methods: The development stages of samples at 3, 9, 12, 19, 27, and 33 days after inoculation (DAI) were collected. HPLC coupled with diode array detection and evaporative light-scattering detection method (HPLC-DAD-ELSD) was used to determine eight makers, including six nucleosides and two carbohydrates from the samples. Results: C. militaris cultured 33 DAI with fifth star silkworm larva could accumulate higher levels of cordycepin (13.43 mg/g) than the highest reported cordycepin (8.57 g/L). The contents of cordycepin, adenosine, and trehalose were gradually increased with the formation of C. militaris fruiting bodies on silkworm larva, while mannitol was decreased. The change of guanosine was similar to uracil. Conclusions: Results suggested that mannitol could be accumulated in a short period during mycelium growth and could metabolize and transform into energy store and trehalose during fruit body formation. The inosine in the insect was completely utilized and transformed. The synergistic formation of cordycepin and adenosine or differences in metabolized pathways are a great possibility according to the same trend. Highlights: This research offered some reference to further find a certain regularity or metabolic mechanism.

Identification of ceRNA network based on a RNA-seq shows prognostic lncRNA biomarkers in human lung adenocarcinoma.

Previous studies have emphasized the significant functions of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. However, the functions of certain cancer lncRNAs in the lncRNA-related ceRNA network in lung adenocarcinoma (LUAD) are unknown. A systematic and integrative survey of RNA-seq data from The Cancer Genome Atlas (TCGA) was performed to identify candidate lncRNAs for the prognosis of LUAD. In total, 20,502 genes that contain 181 lncRNAs were evaluated in a cohort of 570 LUAD cases. Initially, 6,280 differentially expressed genes (fold-change >2, P<0.05) were obtained using R package, which includes 75 lncRNAs. Next, by univariate regression and multivariate Cox proportional hazards analysis, 32 genes were associated with survival in LUAD. Using these 29 mRNAs and 3 lncRNAs, a prognosis index (PI) was calculated to accurately estimate the survival in LUAD: PI=∑exprisk gene × HRrisk gene. Furthermore, the 32-gene signature was an independent prognostic indicator for LUAD (HR >1; P<0.05, by multivariate analysis). Weighted gene co-expression network analysis (WGCNA) of three risk lncRNAs-FAM138B, NHEG1 and TLX1NB-was performed, based on the P-values of the associated genes, and the top 27 miRNAs that bound to these lncRNAs were predicted by Miranda as target miRNAs. Next, these target miRNAs were transferred to the TarBase, miRTarBase, miRecards and starBase v2.0 databases to obtain their target genes. According to the previous miRNA-mRNA and miRNA-lncRNA data, three lncRNA-miRNA-mRNA ceRNA networks were established, based on the 29 prognostic mRNAs, forming a regulatory network in LUAD. The present study provided insight into the lncRNA-related ceRNA network in LUAD and has identified potential diagnostic and prognostic biomarkers.

Novel Fluorescein-Based Fluorescent Probe for Detecting H2S and Its Real Applications in Blood Plasma and Biological Imaging.

A broad-spectrum fluorescent probe, which can be applied to monitoring H2S in various biological systems, has been rationally designed and synthesized. This specific probe was applied to localize the endogenous H2S in living Raw264.7 macrophage cells, HepG2 cells, and H9C2 cells. At the same time, the probe has successfully visualized CBS- and CSE-induced endogenous H2S production and monitored CBS and CSE activity in H9C2 cells. This probe could serve as a powerful molecular imaging tool to further explore the physiological function and the molecular mechanisms of endogenous H2S in living animal systems.