Search

To explore and utilize the abundant soil microorganisms and their beneficial functions, high-throughput sequencing technology was used to analyze soil microbial compositions in the rhizosphere of red and green amaranth varieties. The results showed that significant differences in soil microbial composition could be found in the rhizosphere of amaranth plants with different color phenotypes. Firstly, soil bacterial compositions in the rhizosphere were significantly different between red and green amaranths. Among them, Streptomyces, Pseudonocardia , Pseudolabrys , Acidibacter, norank_ f_ Micropepsaceae , Bradyrhizobium , and Nocardioides were the unique dominant soil bacterial genera in the rhizosphere of red amaranth. In contrast, Conexibacter , norank_f_norank_o_norank_c_TK10 , and norank_f_ norank_o_ norank_ c_AD3 were the special dominant soil bacterial genera in the rhizosphere of green amaranth. Additionally, even though the soil fungal compositions in the rhizosphere were not significantly different between red and green amaranths, the abundance of the dominant soil fungal genera in the rhizosphere showed significant differences between red and green amaranths. For example, unclassified_k__Fungi , Fusarium , Cladophialophora , unclassified_c__Sordariomycetes and unclassified_p__Chytridiomycota significantly enriched as the dominant soil fungal genera in the rhizosphere of the red amaranth. In contrast, Aspergillues only significantly enriched as the dominant soil fungal genus in the rhizosphere of green amaranth. All of the above results indicated that amaranth with various color phenotypes exactly recruited different microorganisms in rhizosphere, and the enrichments of soil microorganisms in the rhizosphere could be speculated in contributing to amaranth color formations.

Background: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment., Methods: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles., Results: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA., Conclusion: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA., (© 2024. The Author(s).)

Total volatile basic nitrogen (TVB-N) is a vital indicator for assessing seafood freshness and edibility. Rapid on-site detection of volatile basic nitrogen (VBN) is of significant importance for food safety monitoring. In this study, highly luminescent self-assembled copper nanoclusters (Cu NCs@ p -MBA), synthesized using p -mercaptobenzoic acid ( p -MBA) as the ligand, were utilized for the sensitive detection of VBNs. Under acidic conditions, Cu NCs@ p -MBA formed compact and well-organized nanosheets through noncovalent interactions, accompanied by intense orange fluorescence emission (651 nm). The benzene carboxylic acid part of Cu NCs@ p -MBA provided the driving force for supramolecular assembly and exhibited a strong affinity for amines, particularly low-molecular-weight amines such as ammonia (NH 3 ) and trimethylamine (TMA). The quantitative determination of NH 3 and TMA showed the detection limits as low as 0.33 and 0.81 ppm, respectively. Cu NCs@ p -MBA also demonstrated good responsiveness to putrescine and histamine. Through density functional theory (DFT) calculations and molecular dynamics (MD) simulations, the precise atomic structure, assembly structure, luminescent properties, and reaction processes of Cu NCs@ p -MBA were studied, revealing the sensing mechanism of Cu NCs@ p -MBA for highly sensitive detection of VBNs. Based on the self-assembled Cu NCs@ p -MBA nanosheets, portable fluorescent labels were developed for semiquantitative, visual, and real-time monitoring of seafood freshness. Therefore, this study exemplified the high sensitivity of self-assembly induced emission (SAIE)-type Cu NCs@ p -MBA for VBNs sensing, offering an efficient solution for on-site monitoring of seafood freshness.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that can cause gastrointestinal ulcers by affecting dopamine levels. Therefore, MPTP has been considered a toxic substance that causes gastric ulcer disease in experimental animals. In this study, tree shrews were used as the animal model of gastric mucosa injury, and MPTP was intraperitoneally injected at a lower MPTP dosage 2 mg/kg/day for 13 weeks, while tree shrews were not injected as the control group. Under the light microscope, local congestion or diffuse bleeding points of gastric mucosa and multiple redness and swelling bleeding symptoms on the inner wall were observed in the treatment group, as well as immune cell infiltration was found in HE staining, but no such phenomenon was observed in the control group. In order to explore the molecular basis of changes in MPTP induced gastric mucosa injury, the transcriptome and proteome data of gastric mucosa were analyzed. We observed significant differences in mRNA and protein expression levels under the influence of MPTP. The changes in mRNA and proteins are related to increased immune infiltration, cellular processes and angiogenesis. More differentially expressed genes play a role in immune function, especially the candidate genes RPL4 and ANXA1 with significant signal and core role. There are also differentially expressed genes that play a role in mucosal injury and shedding, especially candidate genes GAST and DDC with certain signaling and corresponding functions. Understanding the factors and molecular basis that affect the expression of related genes is crucial for coping with Emotionality gastric mucosa injury disease and developing new treatment methods to establish the ability to resist disease., (© 2024. The Author(s).)

Background: Cardiac complications are related to poor prognosis after spontaneous intracerebral hemorrhage (ICH). This study aims to predict the cardiac complications arising from small intracranial hematoma at ultraearly stage., Methods: The data of this work were derived from the Risk Stratification and Minimally Invasive Surgery in Acute ICH Patients study (ClinicalTrials.gov Identifier: NCT03862729). This work included patients with ICH but without brain herniation, as confirmed by a brain computed tomography scan within 48 hours of symptom onset. Every Patient's information recorded at the emergent department, including clinical, laboratory, electrocardiogram, and medical records, was derived from the electronic data capture. Cardiac complications were defined as the occurrence of myocardial damage, arrhythmias, and ischemic electrocardiogram changes during hospitalization. Variables associated with cardiac complications were filtrated by univariate and multivariate regression analyses. Independent risk factors were used to form the early predictive model. The restricted cubic splines were employed to investigate the nonlinear associations in a more sophisticated and scholarly manner., Results: A total of 587 ICH patients were enrolled in this work, including 72 patients who suffered from cardiac complications after ICH. Out of the 78 variables, 24 were found to be statistically significant in the univariate logistic regression analysis. These significant variables were then subjected to multivariate logistic regression analysis and utilized for constructing risk models. Multivariate logistic regression analysis showed high plasma fibrinogen (FIB) level [odds ratio (OR) per standard deviation (SD) 1.327, 95% confidence intervals (CI) 1.037-1.697; P = 0. 024)] and older age (OR per SD 1.777, 95% CI 1.344-2.349; P ＜0.001) were associated with a higher incidence of cardiac complications after ICH. High admission pulse rate (OR 0.620, 95% CI 0.451-0.853; P = 0. 003) was considered a protective factor for cardiac complications after ICH. In the restricted cubic spline regression model, FIB and cardiac complications following ICH were positively correlated and almost linearly (P for nonlinearity = 0.073). The reference point for FIB in predicting cardiac complications after ICH was 2.64 g/L., Conclusions: Emergent factors, including plasma FIB level, age, and pulse rate, might be independently associated with cardiac complications after ICH, which warrants attention in the context of treatment., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypoxic-ischemic encephalopathy, which predisposes to neonatal death and neurological sequelae, has a high morbidity, but there is still a lack of effective prevention and treatment in clinical practice. To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy, in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats. First, based on the conventional Rice-Vannucci model of hypoxic-ischemic encephalopathy, we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge. Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins. We also performed transmission electron microscopy and found typical characteristics of ferroptosis, including mitochondrial shrinkage, ruptured mitochondrial membranes, and reduced or absent mitochondrial cristae. Further, both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein, which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage. Finally, we found that ferroptosis-related Ferritin (Fth1) and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury. Based on these results, it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion. Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system., Competing Interests: None

Evidence for the effects of dietary diversity changes and cognitive frailty (CF) in the older adults is not clear. This study aimed to investigate the relationship between dietary diversity changes and CF in older adults Chinese. A total of 14,382 participants (mean age: 82.3 years) were enrolled. Dietary diversity scores (DDSs) were collected and calculated using a food frequency questionnaire. DDS changes between baseline and first follow-up were categorized into nine patterns. The associations between DDS changes and the incidence of CF were estimated using Cox proportional hazards models. During an 80,860 person-year follow-up, 3023 CF cases were identified. Groups with a decrease in DDS had increased CF risk compared with the high-to-high DDS group, with adjusted hazard ratios (HRs; 95% confidence intervals (Cis)) of 1.30 (1.06, 1.59), 2.04 (1.51, 2.74), and 1.81 (1.47, 2.22) for high-to-medium, high-to-low, and medium-to-low groups, respectively. Lower overall DDS groups were associated with greater CF risks, with HRs (95% CIs) of 1.49 (1.19, 1.86) for the low-to-medium group and 1.96 (1.53, 2.52) for the low-to-low group. Compared with the high-to-high group, significant associations with CF were found in other DDS change groups; HRs ranged from 1.38 to 3.12 for the plant-based DDS group and from 1.24 to 1.32 for the animal-based DDS group. Additionally, extreme and moderate declines in overall DDS increased CF risk compared with stable DDS, with HRs (95% CIs) of 1.67 (1.50, 1.86) and 1.13 (1.03, 1.24), respectively. In conclusion, among older adults, a declining or persistently low DDS and a moderately or extremely declining DDS were linked to higher incident CF. Plant-based DDS changes correlated more strongly with CF than animal-based DDS changes.

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1-1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water., Competing Interests: Ta-Chien Lu and Catherine Lee filed patent application for the discovery of pharmaceutical composition and use of Apixaban film products for the treatment and prevention of thrombosis and related disorders on 03 June 2022 (20220387415 A1). The authors declare that they have no competing financial interests or personal relationships that may appear to influence the work reported in this paper., (© 2023 The Authors.)

Objective: To investigate the expression and clinical significance of soluble interleukin-2 receptor(sIL-2R) in patients with multiple myeloma(MM)., Methods: 54 newly diagnosed MM patients in the Second Affiliated Hospital of Fujian Medical University from February 2020 to December 2021 were selected as the observation group, and 60 healthy people in our hospital in the same period were selected as the control group. The expression levels of sIL-2R in the serum of the two groups were detected by enzyme-linked immunosorbent assay. The differences of sIL-2R expression level among different clinical parameter groups in MM patients were compared. The clinical parameters include:gender, age, ISS stage, hemoglobin, albumin, serum creatinine, lactate dehydrogenase and β 2 -microglobulin, blood calcium, bone marrow plasma cell ratio and treatment response. The relationship between sIL-2R expression level and progression-free survival(PFS) and overall survival(OS) in MM patients were analyzed., Results: The expression of serum SIL-2R in MM patients was significantly higher than that in healthy control group ( P <0.05). The expression of sIL-2R in MM patients who did not achieve complete remission(CR) was significantly higher than those of CR patients ( P =0.037). There was no significant difference in the expression of serum sIL-2R between the groups of different sex, age, ISS stage, hemoglobin concentration, albumin content, serum creatinine level, lactate dehydrogenase level, the content of β 2 -microglobulin, the concentration of blood calcium, and the proportion of bone marrow plasma cells( P >0.05). The PFS of sIL-2R high expression group(15 months) was shorter than that of sIL-2R low expression group (22 months), which was significant difference ( P =0.041). But there was no significant difference in OS between sIL-2R high expression group and sIL-2R low expression group ( P =0.124). Univariate analysis results showed that the high expression of serum sIL-2R was associated with poor PFS in MM patients. Multivariate analysis results showed that the high expression of serum sIL-2R was still an independent adverse prognostic factor for PFS in MM patients, However, the expression of serum sIL-2R was not statistically significant in evaluating OS in MM patients by univariate and multivariate analysis., Conclusion: The expression of serum sIL-2R in MM patients was significantly higher than that in healthy people. Serum sIL-2R is an independent prognostic factor of PFS in MM patients.

Hypochlorous acid/hypochlorite (HOCl/ClO - ) plays important roles in killing bacterial and causing damage to living tissues, and its abnormal levels could lead to many diseases. Although great efforts have been devoted, fluorescent probes for HOCl/ClO - with near-infrared fluorescence, good selectivity/sensitivity, and low background are still important and urgent. In this work, a novel double-bond-linked TCF-aza-BODIPY-based near-infrared fluorescent probe (3) was rationally designed, successfully prepared, and applied for sensing HOCl/ClO - in both solutions and living RAW264.7 cells, showing good selectivity and fluorescence "turn-on" phenomenon at 670 nm with low background. The limit of detection towards ClO - was determined to be 0.36 μM through the linear fluorescence changes at 670 nm in a broad ClO - -concentration range of 0-150 μM. Furthermore, the sensing mechanism was investigated by mass spectrometry and compared with 1, suggesting that the remarkable spectroscopic changes could be ascribed to the oxidization of the double bond to the aldehyde group, accompanied with the leaving of the TCF group. Confocal imaging experiments also confirmed the remarkable intracellular fluorescence enhancements through incubation of ClO - and phorbol ester 12-myristate 13-acetate (PMA) in RAW264.7 cells. Therefore, for the first time, we reported a near-infrared TCF-aza-BODIPY-based fluorescent probe for highly sensitive and fluorescence "turn-on" detection of both exogenous and endogenous HOCl in living RAW264.7 cells through the quick oxidation of a conjugated double bond., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Salvia chinensia Benth (Shijianchuan in Chinese, SJC) has been used as a traditional anti-cancer herb. SJC showed good anti-esophageal cancer efficacy based on our clinical application. However, the current research on SJC is minimal, and its anti-cancer effect lacks scientific certification. This study aims to clarify the inhibitory effect of SJC on esophageal cancer and explore its underlying mechanism. Q-Orbitrap high-resolution LC/MS was used to identify the primary chemical constituents in SJC. Cell proliferation and colony formation assays showed that SJC could effectively inhibit the growth of esophageal tumor cells in vitro . To clarify its mechanism of action, proteomic and bioinformatic analyses were carried out by combining tandem mass labeling and two-dimensional liquid chromatography-mass spectrometry (LC-MS). Data are available via ProteomeXchange with identifier PXD035823. The results indicated that SJC could activate AMPK signaling pathway and effectively promote autophagy in esophageal cancer cells. Therefore, we further used western blotting to confirm that SJC activated autophagy in esophageal cancer cells through the AMPK/ULK1 signaling pathway. The results showed that P-AMPK and P-ULK1 were significantly up-regulated after the treatment with SJC. The ratio of autophagosomes marker proteins LC3II/I was significantly increased. In addition, the expression of the autophagy substrate protein P62 decreased with the degradation of autophagosomes. Using lentiviral transfection of fluorescent label SensGFP-StubRFP-LC3 protein and revalidation of LC3 expression before and after administration by laser confocal microscopy. Compared with the control group, the fluorescence expression of the SJC group was significantly enhanced, indicating that it promoted autophagy in esophageal cancer cells. Cell morphology and the formation of autophagosomes were observed by transmission electron microscopy. Our study shows that the tumor suppressor effect of SJC is related to promoting autophagy in esophageal tumor cells via the AMPK/ULK1 signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jia, Lin, Guo, Huang, Zhao, Zhang and Li.)

Objective: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM)., Methods: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated., Results: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity., Conclusion: BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

Although hybridization plays a large role in speciation, some unknown fraction of hybrid individuals never reproduces, instead remaining as genetic dead-ends. We investigated a morphologically distinct and culturally important Chinese walnut, Juglans hopeiensis, suspected to have arisen from hybridization of Persian walnut (J. regia) with Asian butternuts (J. cathayensis, J. mandshurica, and hybrids between J. cathayensis and J. mandshurica). Based on 151 whole-genome sequences of the relevant taxa, we discovered that all J. hopeiensis individuals are first-generation hybrids, with the time for the onset of gene flow estimated as 370,000 years, implying both strong postzygotic barriers and the presence of J. regia in China by that time. Six inversion regions enriched for genes associated with pollen germination and pollen tube growth may be involved in the postzygotic barriers that prevent sexual reproduction in the hybrids. Despite its long-recurrent origination and distinct traits, J. hopeiensis does not appear on the way to speciation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Topological cytonuclear discordance is commonly observed in plant phylogenetic and phylogeographic studies, yet few studies have attempted to detect two other forms of cytonuclear discordance (branch length and geographical) and to uncover the causes of the discordance. We used the whole nuclear and chloroplast genome data from 80 individual Asian butternuts to reveal the pattern and processes of cytonuclear discordance. Our findings indicate that the chloroplast genome had substantially deeper divergence (branch-length discordance) and a steeper cline in the contact zone (geographic discordance) compared with the nuclear genome. After various hypothesis have been tested, the results suggest that incomplete lineage sorting, positive selection and cytonuclear incompatibility are probably insufficient to explain this pattern. However, isolation-by-distance analysis and gene flow estimation point to a much higher level of gene flow by pollen compared with by seeds, which may have slowed down lineage divergence and mediated wider contact for nuclear genome compared with the chloroplast genome. Altogether, this study highlights a critical role of sex-biased dispersal in causing discordance between the nuclear and plastid genome of Asian butternuts. Given its ubiquity among plants, asymmetric gene flow should be given a high priority in future studies of cytonuclear discordance., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Background: rs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined., Methods: Three-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns., Results: Generally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 ( P =0.0423) and FSHR ( P =0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes ( P =0.0008) in adipocytes ( P =0.0001), which was validated in the fat tissue ( P <0.0001) and ovary ( P =0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in FSHR co-expressed genes ( P =0.0002) and PCOS patients ( P =0.0002), with CD4 high expression in PCOS patients ( P =0.0316) and PCOS-like models ( P =0.0079). Meanwhile, FSHR expression was positively correlated with CD4 expression in PCOS patients (P=0.0252) and PCOS-like models ( P =0.0178). Furthermore, androgen receptor ( AR ) was identified as the common transcription factor for STON1 and FSHR and positively correlated with the expression of STON1 ( P =0.039) and FSHR ( P =4e-06) in ovary tissues and PCOS-like mice., Conclusion: Overall, we identified STON1 and FSHR as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and CD4 immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cao, Wei, Liu, Lin, Luo, Zhang, Lin, Geng, Ye, Shi and Xia.)

Objective: To investigate the clinical characteristics and risk factors of nosocomial infection in patients with non-Hodgkin lymphoma (NHL), in order to guide better clinical prevention and treatment of nosocomial infection., Methods: The incidence of nosocomial infection, infection site, characteristics of pathogenic bacteria, drug sensitivity test results and infection risk factors of 472 non-Hodgkin lymphoma patients admitted to the Second Affiliated Hospital of Fujian Medical University from January 2015 to September 2020 were retrospectively analyzed., Results: Among the 472 patients, 97 (20.6%) had nosocomial infection, mainly in the lower respiratory tract (41.2%), followed by oral cavity, upper respiratory tract, urogenital tract, and blood. A total of 71 strains of pathogenic bacteria were isolated, including Gram-negative (G - ) bacteria (52.1%), Gram-positive (G + ) bacteria (28.2%), and fungi (19.7%). The detection rate of extended-spectrum β-lactamase (ESBLs) in Klebsiella pneumoniae and Escherichia coli was 36.4% and 22.2%, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenems (imipenem) in G- bacteria was 33.3%, while the sensitivity rate of other G- bacteria was 100%. Among the 7 strains of Staphylococcus aureus, 1 strain was found to be methicillin-resistant Staphylococcus aureus (MRSA), and the sensitivity of G + bacteria to linezolid, tigecyclinetegacycline and vancomycin was 100%. Candida albicans was the main source of fungal infection. Univariate analysis showed that nosocomial infection was associated with hospital day, bone marrow involvement, clinical stage, chemotherapy, neutrophil count in peripheral blood, and lymphoma type. Multivariable Logistic regression model showed that hospital days ≤7 was the protective factor of nosocomial infection, while clinical stage (Ⅲ, Ⅳ period), tumor involving bone marrow, and peripheral blood neutrophil count <0.5×10 9 /L were major risk factors., Conclusion: NHL patients show high nosocomial infection rate and lower respiratory tract infection is common. Hospital day, clinical stage, presence of bone marrow invasion, and neutrophil count in peripheral blood are independent risk factors.

Aim: To investigate the protective effect of heme oxygenase-1 (HO-1) against H 2 O 2 -induced apoptosis in human ARPE-19 cells., Methods: The lentiviral vector expressing HO-1 was prepared and transfected into apoptotic ARPE-19 cells induced by H 2 O 2 . Functional experiments including cell counting kit-8 (CCK-8) assay, flow cytometry (FCM) and mitochondrial membrane potential assay were conducted., Results: The ultrastructure of ARPE-19 cells was observed using transmission electron microscope (TEM). It was found that exogenous HO-1 significantly ameliorated H 2 O 2 -induced loss of cell viability, apoptosis and intracellular levels of reactive oxygen species (ROS) in ARPE-19 cells. The overexpression of HO-1 facilitated the transfer of nuclear factor erythroid-2-related factor 2 (Nrf2) from cytoplasm to nucleus, which in turn upregualted expressions HO-1 and B-cell lymphoma-2 (Bcl-2). Furthermore, HO-1 upregulation further inhibited H 2 O 2 -induced release of cysteinyl aspartate specific proteinase-3 (caspase-3)., Conclusion: Exogenous HO-1 protect ARPE-19 cells against H 2 O 2 -induced oxidative stress by regulating the expressions of Nrf2, HO-1, Bcl-2, and caspase-3., (International Journal of Ophthalmology Press.)

Hepatocellular carcinoma (HCC) is the 6th most prevalent cancer and the 4th leading cause of cancer-related death worldwide. Mechanisms explaining the carcinogenesis of HCC are not clear yet. In recent years, rapid development of N 6 -methyladenosine (m6A) modification provides a fresh approach to disclosing this mystery. As the most prevalent mRNA modification in eukaryotes, m6A modification is capable to post-transcriptionally affect RNA splicing, stability, and translation, thus participating in a variety of biological and pathological processes including cell proliferation, apoptosis, tumor invasion and metastasis. METTL3 has been recognized as a pivotal methyltransferase and essential to the performance of m6A modification. METTL3 can regulate RNA expression in a m6A-dependent manner and contribute to the carcinogenesis, tumor progression, and drug resistance of HCC. In the present review, we are going to make a clear summary of the known roles of METTL3 in HCC, and explicitly narrate the potential mechanisms for these roles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Pan, Lin, Hao, Chu, Wan and Wang.)

In the present study, antagonistic activity of bacterial strain BS-Z15, was evaluated against Verticillium dahlia. The fermented broth of BS-Z15 inhibited the growth of Verticillium dahliae. The genome of strain BS-Z15 had a total size of 4,068,702 base pairs and contained 4318 genes, of which 4196 are coding sequences and 122 are non-coding RNA. Among these genes, nine genomic islands, 86 tRNAs, 13 sRNAs, and one prophage was determined. With the help of annotation databases, most unigene functions were identified. At the same time, genomic comparison between BS-Z15 and 12 Bacillus members showed that the genes of BS-Z15 were closely related to the Bacillus group, and were conserved between the two groups, including most of the genes associated with fungal antagonism. BS-Z15 contains genes involved in a variety of antagonistic mechanisms, including genes encoding or synthesizing mycosubtilin, chitinases (but not CHIA and CHIB), glycoside hydrolases, iron nutrients, and antibiosis. However, it only contained the complete mycosubtilin- and bacilibactin-related operators in the reported main antifungal gene cluster of B. subtilis. Mycosubtilin and bacilibactin may be the main active antifungal substance. Besides, some genes could encode products related to biofilm production, which may be related to the colonization ability of the strain in plant rhizospheres. The complete genome of B. subtilis BS-Z15 provided new insights into the potential metabolites it produces related to its biocontrol activity.

Human papillomavirus (HPV) infection and gene mutations were reputed as key factors in cervical carcinoma (CC) and head and neck squamous cell carcinoma (HNSCC). However, the associations of HPV status and gene mutations remain to be determined. This study aims to identify molecular patterns of LRP1B mutation and HPV status via rewiring tumor samples of HNSCC (n=1478) and CC (n=178) from the TCGA dataset. Here, we found that LRP1B mutation was associated with HPV status in CC ( P =0.040) and HNSCC ( P =0.044), especially in HPV 16 integrated CC ( P =0.036). Cancer survival analysis demonstrated that samples with LRP1B mutation showed poor disease outcomes in CC ( P =0.013) and HNSCC ( P =0.0124). In addition, the expression status of LPR1B was more favorable for prediction than TP53 or RB1 in CC and HNSCC. Mutation clustering analysis showed that samples with LRP1B mutation showed higher mutation count in CC ( P =1.76e-67) and HNSCC ( P <10e-10). Further analysis identified 289 co-occurrence genes in these two cancer types, which were enriched in PI3K signaling, cell division process, and chromosome segregation process, et al. The 289-co-occurrence gene signature identified a cluster of patients with a higher portion of copy number variation (CNV) lost in the genome, different tumor HPV status ( P <10e-10), higher mutation count ( P <10e-10), higher fraction genome altered value ( P =2.078e-4), higher aneuploidy score ( P =3.362e-4), and earlier started the smoking year ( P =2.572e-4), which were associated with shorter overall survival ( P =0.0103) in CC and HNSCC samples. Overall, LRP1B mutation was associated with tumor HPV status and was an unfavorable prognostic biomarker for CC and HNSCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

As sulfosalicylic acid (SUA) is extensively used as a pharmaceutical product, discharge of SUA into the environment becomes an emerging environmental issue because of its low bio-degradability. Thus, SO 4 - -based advanced oxidation processes have been proposed for degrading SUA because of many advantages of SO 4 - . As Oxone represents a dominant reagent for producing SO 4 - , and Co is the most capable metal for activating Oxone to generate SO 4 - , it is critical to develop an effective but easy-to-use Co-based catalysts for Oxone activation to degrade SUA. Herein, a 3D hierarchical catalyst is specially created by decorating Co 3 O 4 nanocubes (NCs) on macroscale nitrogen-doped carbon form (NCF). This Co 3 O 4 -decorated NCF (CONCF) is free-standing, macroscale and even squeezable to exhibit interesting and versatile features. More importantly, CONCF consists of Co 3 O 4 NCs evenly distributed on NCF without aggregation. The NCF not only serves as a support for Co 3 O 4 NCs but also offers additional active sites to synergistically enhance catalytic activities towards Oxone activation. Therefore, CONCF exhibits a higher catalytic activity than the conventional Co 3 O 4 nanoparticles for activating Oxone to fully eliminate SUA in 30 min with a rate constant of 0.142 min -1 . CONCF exhibits a much lower Ea value of SUA degradation (35.2 kJ/mol) than reported values, and stable catalytic activities over multi-cyclic degradation of SUA. The mechanism of SUA degradation is also explored, and degradation intermediates of SUA degradation are identified to provide a possible pathway of SUA degradation. These features validate that CONCF is certainly a promising 3D hierarchical catalyst for enhanced Oxone activation to degrade SUA. The findings obtained here are also insightful to develop efficient heterogeneous Oxone-activating catalysts for eliminating emerging contaminants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The role of nontreponemal antibodies in the Treponema pallidum infection course is unclear. We investigated the effect of immunization with nontreponemal antigen on T. pallidum-challenged rabbits. Nontreponemal antigen was injected intravenously into rabbits in the nontreponemal group (n = 12) to elicit antibodies (≥1:64), and normal saline-injected rabbits were used as controls (n = 12). Then, rabbits were challenged with 10 6 T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for mRNA analysis every week. Six rabbits from both groups were euthanized at 14 d and 28 d. The popliteal lymph nodes were extracted to assess infectivity using a rabbit infectivity test. The maximum lesion diameters were not different between the two groups (12.4 ± 0.9 mm in the nontreponemal group vs. 12.5 ± 1.0 mm in the control group, P = 0.386), but the time to maximum diameter appearance was delayed by approximately 4 d in the nontreponemal group (14.4 ± 1.6 d vs. 10.8 ± 1.9 d, P = 0.000). There were no significant differences in the proportions of lesions (58/60 (96.7%) vs. 59/60 (98.3%), P = 0.500) or ulcers (55/60 (91.7%) vs. 57/60 (95.0%), P = 0.359) between the two groups. An ulcer development delay of 5 d was observed in the nontreponemal group (19.3 ± 2.0 d vs. 14.0 ± 1.8 d, P = 0.000). IL-2 and IFN-γ mRNA expression in the nontreponemal group was significantly higher than that in the control group at 7 d and 14 d post-challenge. flaA mRNA expression and the rabbit infectivity test positive rate were not different between the two groups. Immunization with nontreponemal antigen altered the syphilis course in rabbits, resulting in delayed maximal lesion diameter and ulcer development, but it could not inhibit the spread of T. pallidum from primary lesion sites to viscera., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Colon cancer is one of the most common and has the highest mortality rate in the world. MicroRNAs (miRNAs) as potential biomarkers play crucial roles in diagnosis, prognosis, and drug-response prediction of colon cancer., Methods: In this study, we collected miRNA expression data from the Broad GDAC Firehose and screened specific miRNA-gene pairs after treatment with 5-fluorouracil treatment and used COAD analysis to study the association of miRNAs and inhibitor of the inhibitory genes. Potential drug-related miRNAs were further extracted via hypergeometric testing., Results: The results showed that 13,651 miRNA-gene pairs were retrieved, including 242 miRNAs and 5,179 genes. The association between miRNAs and the inhibitor of inhibitory genes DPYD, TYMS, UNG was indicated. We further extracted 4 potential drug-related miRNAs, including hsa-mir-551a, hsa-mir-144, hsa-mir-519b, hsa-mir-506. The miRNA-gene pairs associated with 5-fluorouracil exhibit better prognosis in patients with CRC., Conclusions: We expected that up-regulation of hsa-mir-551a, hsa-mir-144, and hsa-mir-506 and down-regulation of hsa-mir-519b would exhibit better prognosis. The findings would underpin the fundamental hypothesis of mi-RNAs being prognostic signal biomarkers in therapy of 5-fluorouracil in CRC.

Background: Acute hemorrhage-induced excessive excitation of sympathetic-adrenal-medullary system (SAS) leads to gut hypoperfusion and barrier dysfunction, which is a critical event during hemorrhagic shock-induced multiple organ injury. Stellate ganglion blockade (SGB) has been widely used for suppression of sympathetic-adrenal-medullary system in the clinical practice. However, whether SGB improves intestinal barrier function after hemorrhagic shock remains unclear. Here, we hypothesized that the implementation of SGB restores intestinal barrier function and reduces gut injury., Materials and Methods: Male rats received the SGB pretreatment and underwent hemorrhagic shock followed by resuscitation. The 96-h survival rate, intestinal permeability and morphology, D-lactic acid concentration and diamine oxidase activity in plasma, and expressions of F-actin, Claudin-1, and E-cadherin in intestinal tissues were observed., Results: Pretreatment with SGB significantly enhances the 96-h survival rate in rats subjected to hemorrhagic shock (from 8.3% to 66.7%). Hemorrhagic shock reduced the coverage scale of intestinal mucus and intestinal villus width and height, enhanced the intestinal permeability to fluorescein isothiocyanate-dextran 4 and D-lactic acid concentration in plasma, and decreased the expressions of F-actin, Claudin-1, and E-Cadherin in intestinal tissue. These hemorrhagic shock-induced adverse effects were abolished by SGB treatment., Conclusions: SGB treatment has a beneficial effect during hemorrhagic shock, which is associated with the improvement of intestine barrier function. SGB may be considered as a new therapeutic strategy for treatment of hemorrhagic shock., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Previous studies have revealed that alanine aminotransferase (ALT) may be one of the risk factors of developing diabetes. We aimed to demonstrate the independent effect of ALT on incident diabetes and to investigate whether the association between ALT and incident diabetes is modified by age and gender in the general Chinese population., Methods: The present study was a retrospective cohort study, including 210,051 Chinese adult participants. The primary outcome was developing diabetes. The serum ALT activities were stratified by quintiles. We obtained data from 'DATADRYAD' website and used the data for secondary analysis., Results: At a median follow-up of 3.0 y, 4144 of 210,051 (1.97%) participants developed diabetes. After adjustment for potential confounders, a significantly higher risk of the incident diabetes (HR: 1.43, 95% CI: 1.25-1.63) was found in participants in the fifth quintile (Q5, ≥31 U/L) compared to those in the first to fourth quintiles (Q1-4) for ALT activities. Among males aged 30 to 40 and 40 to 50 y with the fifth quintile of ALT activity had 2.4- and 1.5-fold increased odds of developing diabetes, respectively, in comparison with those in the lower ALT activities. Among females with age 30 to 40 and ≥ 70 y, the fifth quintile of ALT activity had 4.9- and 2.2-fold increased odds for incident diabetes., Conclusion: Our result indicated that the ALT activity was positively associated with the incident diabetes among Chinese persons. Moreover, 30-40 y individuals, whether male or female, with elevated ALT activities had the greatest increased risk for diabetes compared with persons with lower ALT activities in the same age group., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Many factors are reported to be related to the prognosis of patients with esophageal adenocarcinoma (EAC), but few reliable and straightforward tools for clinicians to estimate individual mortalities have been developed. This study aimed to evaluate the probability of cancer-specific death for patients with EAC and to build nomograms for predicting long-term cancer-specific mortality and overall mortality for EAC patients., Methods: Between 2004 and 2013, a total of 20,623 patients were identified from the surveillance, epidemiology, and end results (SEER) database and randomly divided into training (N=14,436) and validation (N=6,187) cohorts. The cumulative incidence functions (CIFs) of EAC-specific death and other causes were evaluated at the 1st, 3rd, and 5th year after diagnosis. We integrated the significant prognostic factors to construct nomograms and subjected them to internal and external validation., Results: The CIFs of EAC-specific survival at 1, 3, and 5 years after diagnosis were 60.9%, 37.1%, and 31.3%, respectively. Predictors for cancer-specific mortality for EAC comprised tumor grade, tumor extension, the involvement of lymph nodes, distant metastasis, surgery of primary site, insurance recode, and marital status. For overall mortality, it also included the predictor of age at diagnosis. The nomograms were well-calibrated and had good discriminative ability with concordance indexes (c-indexes) of 0.733, 0.728, and 0.728 for 1-, 3- and 5-year prognosis prediction of EAC-specific mortality respectively, and 0.726, 0.720, 0.719 for 1-, 3-, and 5-year prognosis prediction of overall mortality respectively., Conclusions: We proposed and validated the effective and convenient nomograms to predict cancer-specific mortality and the overall mortality for patients with EAC, which only require the basic information available in clinical practice., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: Adenovirus (Ads) is one of the most popular vectors used in gene therapy for the treatment of cancer. However, systemic therapy is limited by circulating antiviral antibodies and poor viral delivery in vivo. In this study, we used cytokine-induced killer (CIK) cells as delivery vehicles of Ads KGHV500 carrying the anti-p21Ras scFv gene to treat Ras gene-related lung cancer and investigate the anti-tumor effect in vitro and in vivo., Methods: The human lung cancer cell line A549 was employed to investigate the anti-tumor activity of recombinant Ads KGHV500 harboring the anti-p21Ras scFv gene using MTT, wound healing, transwell invasion, and apoptosis assays in vitro. Next, CIK cells were used as delivery vehicles to deliver KGHV500 carrying the anti-p21Ras scFv gene to treat A549-transplanted tumors in nude mice, and viral replication, p21Ras scFv expression, and the therapeutic efficacy were assessed., Results: In vitro studies showed that KGHV500 had potent anti-tumor activity. In addition, in vivo, this combination therapy significantly inhibited the growth of lung cancer xenografts compared with mice treated with KGHV500 alone. KGHV500 and anti-p21Ras scFv were observed in tumor tissue, but were nearly undetectable in normal tissues., Conclusions: The co-delivery of anti-p21Ras scFv by CIK cells and KGHV500 could increase the anti-tumor effect and safety, and possess considerable advantages for the treatment of Ras-related cancer.

An electrochemical palladium/ferric oxide (Pd/Fe2O3) nanocomposite modified glassy carbon electrode (GCE) was fabricated by hydrothermal method of Fe2O3 and electrochemical deposition of palladium nanoparticles, respectively. As-prepared Pd/Fe2O3 composite modified electrode exhibits enhanced electrocatalytic activity towards the catalytic oxidation of nitrite compared to Fe2O3, PdNPs modified electrodes and bare electrode. The parameters such as the influence of amount of Pd nanoparticles deposition onto the Pd/Fe2O3 modified electrode (ME) and effect of solution pH were investigated and discussed in detail. Under the optimal conditions, the Pd/Fe2O3 modified GCE can be used to detect nitrite concentration in a wide linear range of 10 and 1000 μM with the detection limit of 0.1 μM. The presence of Cu2+, Na+, Cl-, PO3-4 SO2-4, Mg2+ K+, NO-3, and NH+4 showed a trivial effect on the response of nitrite determination, revealing that developed modified electrode has an excellent anti-interference ability to common ions. It also shows good stability and reproducibility.

The release of toxic organic pollutants and heavy metals by primitive electronic waste (e-waste) processing to waterways has raised significant concerns, but little is known about their potential ecological effects on aquatic biota especially microorganisms. We characterized the microbial community composition and diversity in sediments sampled along two rivers consistently polluted by e-waste, and explored how community functions may respond to the complex combined pollution. High-throughput 16S rRNA gene sequencing showed that Proteobacteria (particularly Deltaproteobacteria) dominated the sediment microbial assemblages followed by Bacteroidetes, Acidobacteria, Chloroflexi and Firmicutes. PICRUSt metagenome inference provided an initial insight into the metabolic potentials of these e-waste affected communities, speculating that organic pollutants degradation in the sediment might be mainly performed by some of the dominant genera (such as Sulfuricurvum, Thiobacillus and Burkholderia) detected in situ. Statistical analyses revealed that toxic organic compounds contributed more to the observed variations in sediment microbial community structure and predicted functions (24.68% and 8.89%, respectively) than heavy metals (12.18% and 4.68%), and Benzo(a)pyrene, bioavailable lead and electrical conductivity were the key contributors. These results have shed light on the microbial assemblages in e-waste contaminated river sediments, indicating a potential influence of e-waste pollution on the microbial community structure and function in aquatic ecosystems., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Hyperlipidemia is a risk factor of arteriosclerosis, stroke, and other coronary heart disease, which has been shown to correlate with single nucleotide polymorphisms of genes essential for lipid metabolism, such as lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5). In this study, the effect of magnolol, the main active component extracted from Magnolia officinalis, on LPL activity was investigated. A dose-dependent up-regulation of LPL activity, possibly through increasing LPL mRNA transcription, was observed in mouse 3T3-L1 pre-adipocytes cultured in the presence of magnolol for 6 days. Subsequently, a transgenic knock-in mice carrying APOA5 c.553G>T variant was established and then fed with corn oil with or without magnolol for four days. The baseline plasma triglyceride levels in transgenic knock-in mice were higher than those in wild-type mice, with the highest increase occurred in homozygous transgenic mice (106 mg/dL vs 51 mg/dL, p<0.01). After the induction of hyperglyceridemia along with the administration of magnolol, the plasma triglyceride level in heterozygous transgenic mice was significantly reduced by half. In summary, magnolol could effectively lower the plasma triglyceride levels in APOA5 c.553G>T variant carrier mice and facilitate the triglyceride metabolism in postprandial hypertriglyceridemia.

Chemotherapy is a cornerstone treatment for early and advanced stage breast cancer patients. However, resistance to chemotherapy remains a major obstacle, resulting in disease relapse and progression. Emerging studies demonstrated that miRNAs regulate chemotherapy-induced epithelial-mesenchymal transition (EMT) and drug resistance, but the underlying mechanisms remain unclear. Here we established a doxorubicin-resistant breast cancer cell line MCF-7/Adr, and found these cells exhibited an EMT phenotype featured by a fibroblast-like morphology, increased the capacity of migration and invasion, and underwent the changes of molecular markers of EMT including E-cadherin, N-cadherin, and vimentin. We then compared the miRNA expression profiles between MCF-7/Adr and parental MCF-7 by miRNA microarray, and identified miR-200b as the most dramatically down-regulated miRNA. Overexpression of miR-200b in chemo-resistant cells reversed the EMT phenotype and increased sensitivity to doxorubicin. Inhibition of miR-200b in parental cells induced EMT and resistance to doxorubicin. Furthermore, we characterized the target gene of miR-200b, and showed that overexpression of miR-200b down-regulated FN1 expression and the luciferase activity. Compared with the parental cells, FN1 was significantly elevated in MCF-7/Adr cells. Knockdown of FN1 reversed mesenchymal morphology, inhibited cell migration and invasion, and sensitized cells to doxorubicin. Our data suggest that miR-200b regulates EMT of chemo-resistant breast cancer cells by targeting FN1. miR-200b-based therapy may be an effective strategy in treating advanced breast cancer patients.

Self-labeled inhibitors (SLIs) are promising for creating links, ranging from cancer therapy and metastatic pathways to mechanistic elucidation. In this study, a new category of "two-in-one" fluorescent xanthone inhibitors was developed for the systematic evaluation of anticancer activity and the selective imaging of cytoplasm in vitro. These xanthone inhibitors presented high fluorescent brightness, working over a wide pH range enabled by a "switchable reaction" of the heterocyclic backbone. The strength and nature of fluorescence were probed via spectroscopic methods and density functional theory calculations on the molecular level, respectively. Along with the potent anticancer activity, which was demonstrated using MTT and clonogenic assays with high fluorescent brightness in the cytoplasm, SLI 3fd could be established as a modeled self-monitoring drug in cancer therapy., Competing Interests: The authors declare no competing financial interest.

The effects of introns, especially the first intron, on the regulation of gene expression remains unclear. Therefore, the objective of the present study was to investigate the transcriptional regulatory function of intron 1 on the chicken growth hormone ( cGH ) gene in the rat pituitary tumor cell line (GH4-C1). Transient transfection using first-intron-inserted cGH complete coding sequences (CDSs) and non-intron-inserted cGH CDS plasmids, quantitative RT-PCR (qRT-PCR) and western blot assays were used to detect the expression of cGH . The reporter gene assay was also used to investigate the effect of a series of fragments in the first intron of cGH on gene expression in GH4-C1. All of the results revealed that a 200-bp fragment located in the +485/+684 region of intron 1 was essential for repressing the expression of cGH . Further informatics analysis showed that there was a cluster of 13 transcriptional factor binding sites (TFBSs) in the +485/+684 region of the cGH intron 1. Disruption of a glucocorticoid response-like element (the 19-nucleotide sequence 5'-AGGCTTGACAGTGACCTCC-3') containing a T-box motif (TGACCT) located within this DNA fragment increased the expression of the reporter gene in GH4-C1. In addition, an electrophoretic mobility shift assay (EMSA) revealed a glucocorticoid receptor (GR) protein of rat binding to the glucocorticoid response-like element. Together, these results indicate that there is a negative glucocorticoid response-like element (nGRE) located in the +591/+609 region within the first intron of cGH , which is essential for the down-regulation of cGH expression., Competing Interests: The authors declare no conflict of interest.

Copy number variation (CNV) is an important source of genetic variation in organisms and a main factor that affects phenotypic variation. A comprehensive study of chicken CNV can provide valuable information on genetic diversity and facilitate future analyses of associations between CNV and economically important traits in chickens. In the present study, an F2 full-sib chicken population (554 individuals), established from a cross between Xinghua and White Recessive Rock chickens, was used to explore CNV in the chicken genome. Genotyping was performed using a chicken 60K SNP BeadChip. A total of 1,875 CNV were detected with the PennCNV algorithm, and the average number of CNV was 3.42 per individual. The CNV were distributed across 383 independent CNV regions (CNVR) and covered 41 megabases (3.97%) of the chicken genome. Seven CNVR in 108 individuals were validated by quantitative real-time PCR, and 81 of these individuals (75%) also were detected with the PennCNV algorithm. In total, 274 CNVR (71.54%) identified in the current study were previously reported. Of these, 147 (38.38%) were reported in at least 2 studies. Additionally, 109 of the CNVR (28.46%) discovered here are novel. A total of 709 genes within or overlapping with the CNVR was retrieved. Out of the 2,742 quantitative trait loci (QTL) collected in the chicken QTL database, 43 QTL had confidence intervals overlapping with the CNVR, and 32 CNVR encompassed one or more functional genes. The functional genes located in the CNVR are likely to be the QTG that are associated with underlying economic traits. This study considerably expands our insight into the structural variation in the genome of chickens and provides an important resource for genomic variation, especially for genomic structural variation related to economic traits in chickens., (© 2016 Poultry Science Association Inc.)

Turtles grow slowly and have a long lifespan. Ultrastructural studies of the pituitary gland in Reeves' turtle (Chinemys reevesii) have revealed that the species possesses a higher nucleoplasmic ratio and fewer secretory granules in growth hormone (GH) cells than other animal species in summer and winter. C. reevesii GH gene was cloned and species-specific similarities and differences were investigated. The full GH gene sequence in C. reevesii contains 8517 base pairs (bp), comprising five exons and four introns. Intron 1 was found to be much longer in C. reevesii than in other species. The coding sequence (CDS) of the turtle's GH gene, with and without the inclusion of intron 1, was transfected into four cell lines, including DF-1 chicken embryo fibroblasts, Chinese hamster ovary (CHO) cells, human embryonic kidney 293FT cells, and GH4C1 rat pituitary cells; the turtle growth hormone (tGH) gene mRNA and protein expression levels decreased significantly in the intron-containing CDS in these cell lines, compared with that of the corresponding intronless CDS. Thus, the long intron 1 of GH gene in Reeves' turtle might correlate with downregulated gene expression.

Biological and artificial molecules and assemblies capable of supramolecular recognition, especially those with nucleobase pairing, usually rely on autonomous or collective binding to function. Advanced site-specific recognition takes advantage of cooperative spatial effects, as in local folding in protein-DNA binding. Herein, we report a new nucleobase-tagged metal-organic framework (MOF), namely ZnBTCA (BTC=benzene-1,3,5-tricarboxyl, A=adenine), in which the exposed Watson-Crick faces of adenine residues are immobilized periodically on the interior crystalline surface. Systematic control experiments demonstrated the cooperation of the open Watson-Crick sites and spatial effects within the nanopores, and thermodynamic and kinetic studies revealed a hysteretic host-guest interaction attributed to mild chemisorption. We further exploited this behavior for adenine-thymine binding within the constrained pores, and a globally adaptive response of the MOF host was observed., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The crude processing of electronic waste (e-waste) has led to serious contamination in soils. While microorganisms may play a key role in remediation of the contaminated soils, the ecological effects of combined pollution (heavy metals, polychlorinated biphenyls, and polybrominated diphenyl ethers) on the composition and diversity of microbial communities remain unknown. In this study, a suite of e-waste contaminated soils were collected from Guiyu, China, and the indigenous microbial assemblages were profiled by 16S rRNA high-throughput sequencing and clone library analysis. Our data revealed significant differences in microbial taxonomic composition between the contaminated and the reference soils, with Proteobacteria, Acidobacteria, Bacteroidetes, and Firmicutes dominating the e-waste-affected communities. Genera previously identified as organic pollutants-degrading bacteria, such as Acinetobacter, Pseudomonas, and Alcanivorax, were frequently detected. Canonical correspondence analysis revealed that approximately 70% of the observed variation in microbial assemblages in the contaminated soils was explained by eight environmental variables (including soil physiochemical parameters and organic pollutants) together, among which moisture content, decabromodiphenyl ether (BDE-209), and copper were the major factors. These results provide the first detailed phylogenetic look at the microbial communities in e-waste contaminated soils, demonstrating that the complex combined pollution resulting from improper e-waste recycling may significantly alter soil microbiota.

Elderly patients with acute neurological impairment are prone to severe disability, fecal incontinence (FI), and resultant complications. A suspension positioning system (SPS), based on the orthopedic suspension traction system commonly used for conservative treatment of pediatric femoral fracture and uncomplicated adult pelvic fracture, was developed to facilitate FI management in patients immobilized secondary to an acute neurological condition. To evaluate the effectiveness and safety of the system, a prospective, randomized, controlled study was conducted between October 2009 and July 2012. Two hundred (200) elderly, bedridden, hospitalized patients with acute, nonchronic neurological impairment were randomly assigned to receive routine FI nursing care (ie, individualized dietary modification, psychological support, health education, and social support for caregivers and family members [control group]) or routine incontinence care plus the SPS (experimental group) during the day. Rates of perianal fecal contamination, skin breakdown, incontinence associated dermatitis, pressure ulcer development, and lower urinary tract infection (LUTI) were significantly lower in the SPS than in the control group (P <0.05). Length of hospitalization and costs of care were also lower in the SPS group (P <0.05). Patient quality-of-life (QoL) and FI QoL scores were similar at baseline but significantly higher (better) at the 6-month follow-up interview in the SPS than in the control group (P <0.05). In this study, the rate of FI-associated morbidities was lower and 6-month patient QoL scores were higher in the SPS than in the control group. No adverse events were observed, and all patients completed the study. Further clinical studies are needed to examine the long-term effects of SPS use among neurologically impaired FI patients.

This research was aimed to develop a simple, rapid, accurate and non-invasive method by means of flow-through hybridization technology, which can be used for molecular screening and early prenatal diagnosis for detecting common β-thalassemias mutational genotypes. By using PCR technology combined with flow-through hybridization of low-density gene chip technology, the 6 sets of PCR primer single tube multiplex PCR system and 29 types of DNA probes were designed, then the mutational thalassemias in foetus DNA was rapidly detected in total of 60 anaemia pregnant women plasma. The results showed that 4 cases with deletional α-thalassemias, 3 cases with β-thalassemias, 1 case with mixed type of α & β-thalassemias were detected in foetus DNA of 60 pregnant women plasmas. It is concluded that the method presented in this study is easy to handle, rapid, reliable and cost-effective for detecting 3 common deletional α-thalassemias and 17 common mutational β-thalassemia.

Ferulic acid (F.A) receives significant interest in the beauty industry with regard to its skin-whitening and anti-oxidant properties. However, its use in cosmetics is limited due to pH- and temperature-related instabilities. In this study, we investigated the stability of F.A in eight different prototype formulae. The results confirmed that in our conditions the stability of F.A is pH- and temperature-related. Additionally, the nature of the solvent dipropylene glycol (DPPG) showed a capacity to stabilize F.A. A series of experiments was further planned for studying the mechanism of degradation of F.A. In a prototype of a cosmetic medium, F.A degrades first through a decarboxylation step, leading to 4-hydroxy-3-methoxystyrene (PVG). Further, F.A and PVG are both involved in an additional reaction, resulting in the trans-conjugation dimer of PVG. The consequences of these results in formulating F.A are discussed.

Objective: To observe the therapeutic effect of antihyperlipidemic decoction on hyperlipemia., Methods: 77 hyperlipemia patients are selected and randomly divided into two groups. 37 cases in the treatment group received the treatment of antihyperlipidemic decoction, and 40 cases in the control group received western medicine, zhinbiticose. The course of treatment for both groups was 8 weeks., Results: The difference in total effective rate between the two groups was significant (P < 0.05)., Conclusion: Antihyperlipidemic decoction has a better therapeutic effect for hyperlipemia, with a lower recurrence rate and less side effect.

Background: Predictors for risperidone-related weight gain remain unclear. This study aimed to identify clinical factors influencing body weight in risperidone-treated patients., Method: One hundred forty-six newly hospitalized DSM-IV schizophrenia patients with acute exacerbation entered this prospective, 6-week, repeated-measures trial. The mean +/- SD risperidone dose was 4.3 +/- 1.4 mg/day at week 6. Efficacy, body weight, and tolerability were measured biweekly. Efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE). For determining the impacts of possible prognostic factors on body weight, we utilized generalized estimating equation methods to control for other variables and the within-subject dependence over repeated assessments., Results: After the effects of other factors (including baseline body weight) were adjusted, every 1-week increase in treatment duration raised body weight by 0.442 kg (p <.0001). Increasing baseline body weight by 1 kg reduced weight gain by 0.022 kg (p <.0001). Every 1-year increment in age decreased body weight by 0.052 kg (p <.001). Undifferentiated subtype predicted higher weight by around 0.9 kg than other sub-types (p <.05). Each 1-mg/day increment in risperidone dosage heightened body weight by 0.084 kg (p =.015). Responders (those with PANSS total-score reduction > or = 20%) also had higher weight by 0.513 kg on average (p =.007). Specifically, every 1-point diminution in score in PANSS total, PANSS positive, PANSS negative, PANSS cognitive, and NOSIE increased body weight, on average, by 0.029 kg, 0.057 kg, 0.079 kg, 0.079 kg, and 0.035 kg, respectively (p < or =.009). Other variables did not have significant influences., Conclusion: The results suggest that lower initial body weight, younger age, undifferentiated subtype, higher dosage, and treatment response (for positive, negative, and cognitive symptoms and social functioning) are associated with greater weight gain in acutely ill patients treated with risperidone. Further studies with longer observation and in other populations are needed.

Background: Although the cause of vitiligo is unknown, an autoimmune theory has been proposed, and there is now convincing evidence that cytokines have an important role in pathogenesis of autoimmunity., Objective: To study the possible role of interleukin-1, beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony stimulating factor (GM-CSF) in the pathogenesis of vitiligo., Methods: The authors measured the serum levels of the above-mentioned cytokines from 50 patients with the vitiligo compared with 20 healthy volunteers, employing the method of radioimmunoassay., Results: The results showed that the serum levels of both IL-6 and GM-CSF of the patients with both focal type and generalized type of vitiligo, and the serum level of IL-1 beta of the generalized type,were significantly, higher than those of normal controls in the patients with segmental vitiligo, the serum levels of all the cytokines tested were not significantly different from those of the normal controls. The GM-CSF levels of both focal type and generalized type, and the IL-6 level of the generalized type in progressive stage were significantly higher than those in stable state., Conclusion: It is speculated that IL-6 and GM-CSF may be involved in the autoimmune mechanism of non-segmental vitiligo. However, more evidence is required before a definite conclusion can be drawn.

Landfill leachate recirculation is efficient in reducing the leachate quantity handled by a leachate treatment plant. However, after land application of leachate, nitrification and denitrification of the ammoniacal N becomes possible and the greenhouse gas nitrous oxide (N2O) is produced. Lack of information on the effects of leachate recirculation on N2O production led to a field study being conducted in the Likang Landfill (Guangzhou, China) where leachate recirculation had been practiced for 8 yr. Monthly productions and fluxes of N2O from leachate and soil were studied from June to November 2000. Environmental and chemical factors regulating N2O production were also accessed. An impermeable top liner was not used at this site; municipal solid waste was simply covered by inert soil and compacted by bulldozers. A high N2O emission rate (113 mg m-2 h-1) was detected from a leachate pond purposely formed on topsoil within the landfill boundary after leachate irrigation. A high N2O level (1.09 micrograms L-1) was detected in a gas sample emitted from topsoil 1 m from the leachate pond. Nitrous oxide production from denitrification in leachate-contaminated soil was at least 20 times higher than that from nitrification based on laboratory incubation studies. The N2O levels emitted from leachate ponds were compared with figures reported for different ecosystems and showed that the results of the present study were 68.7 to 88.6 times higher. Leachate recirculation can be a cost-effective operation in reducing the volume of leachate to be treated in landfill. However, to reduce N2O flux, leachate should be applied to underground soil rather than being irrigated and allowed to flow on topsoil.

The TT virus (TTV), a member of a family of human viruses related to the circoviridae viruses, was associated initially with acute and chronic liver diseases. TTV consists of a single-stranded, circular DNA genome of 3.8 kilobases (kb) and at least three open reading frames (ORFs). The objective of the present study was to determine whether or not TTV replicated in peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs). DNA was extracted from the PBMCs or BMCs of 153 cancer patients and from the PBMCs of 50 healthy blood donors (the controls). By using a single round of polymerase chain reaction (PCR), TTV was detected in 98.6% (141 of 143) of the PBMCs and in 90% (9 of 10) of the BMCs from cancer patients. TTV DNA was detected in significantly fewer control subjects at 86% (43 of 50; P < 0.05). Strand-specific PCR (SSPCR) targeting the ORF2 of the common genotypes of TTV was developed specifically to detect TTV positive or negative strand DNA and to examine TTV replication. TTV positive strand DNA, which may be an intermediate of viral replication, was detected in 55.3% (78 of 141) of the TTV-infected PBMCs of the cancer patients and in 7% (3 of 43) of the controls (P < 0.001). The replicative form of TTV was also detectable in 55.6% (5 of 9) of the TTV-infected BMCs. The existence of double-strand (positive and negative strands) TTV DNA in PBMCs and BMCs of the cancer patients was also supported by the finding that TTV DNA extracted from these cells was resistant to S1 nuclease. Using in situ hybridization, TTV DNA was also demonstrated to be present in the nucleus of PBMCs. It is concluded that replicative intermediate forms of TTV DNA are present in both PBMCs and BMCs, indicating that blood cells may be a site of TTV replication., (Copyright 2002 Wiley-Liss, Inc.)

TT virus (TTV) is a recently described circular DNA virus of about 3.8 kb, which is related to the circoviridae viruses. It is commonly detected in healthy subjects and no association with any specific disease has been established. TTV was initially thought to be hepatotropic, but subsequent reports have shown that it is detectable in other tissues, including kidney, prostate, mammary gland, brain, bone marrow, and peripheral blood mononuclear cells. Plasma samples from cancer patients and healthy subjects were tested for the presence or absence of TTV by heminested polymerase chain reaction (PCR). We also developed a quantitative competitive PCR (QC-PCR) assay for TTV that permits accurate measurement of TTV DNA load. Using this assay, the TTV genome load in peripheral blood mononuclear cells (PBMCs) of healthy control subjects (n = 50) and patients with various types of cancer (n = 148), including breast cancer, non-Hodgkin's lymphoma, colon cancer, hepatocellular carcinoma, nasopharyngeal carcinoma, and other cancers, was measured. TTV DNA was detected in 69 of 100 plasma samples (69%) of cancer patients tested and in 39 of 100 plasma samples (39%) randomly selected from 1000 plasma samples of blood donors (p < 0.05). TTV DNA was detectable in the PBMCs of 99% of the cancer patients and 86% of the controls. However, the median virus load was more than 100-fold higher in the cancer patients (3599 copies/100,000 cells) than among the controls (30 copies/100,000 cells; p < 0.0001). There was no significant difference in TTV load among the different cancer types. Using a cutoff value of >250 copies per 100,000 PBMCs, 93.2% of cancer patients were "positive" compared to only 4% of healthy control subjects. Almost all the cancer patients have TTV infection and their TTV genome load in PBMCs is significantly higher than that in control subjects. It remains to be elucidated whether such findings are specific to cancer patients or occur in all seriously ill subjects.

Background: The TT virus (TTV) is a member of a newly described family of human viruses related to the C ircoviridae viruses. Its association with specific diseases has not been established, and screening of blood donors has not been implemented. To date, 16 genotypes have been identified., Study Design and Methods: Sera from 471 healthy blood donors (aged 11-58 years) were randomly selected and tested for TTV by the use of two sets of primers: NG59d/NG61d/NG63d primers and T801/T935 primers. Quantitative competitive PCR (QC-PCR) was developed to measure the TTV DNA concentration among the blood donors. Sequencing of a part of the genome was performed to identify the various genotypes. Several samples showed a mixed genotype infection., Results: TTV was detected in 251 (53.3%) of 471 healthy Hong Kong blood donors by the use of NG59d/NG61d/NG63d primers. The prevalence of the virus increased steadily with age (p = 0.03). TTV DNA was detected in 90 percent (90 of a randomly selected 100) of samples by the use of T801/T935 primers. TTV DNA concentration was also measured by QC-PCR in the blood donors who were positive for TTV DNA in the first round of the heminested PCR. TTV titers ranged from 4.8 x 10(2) copies per mL to 6 x 10(4) copies per mL, with a median value of 1.2 x 10(4) copies per mL. Sequencing and phylogenetic analysis of a 223-bp fragment from open reading frame 1 showed three main genotypes (G1 [60.7%], G2 [24.3%], and G3 [14%]) and a new genotype 17 (G17), with the latter bearing 60-percent nucleotide homology with other genotypes deposited at GenBank. In addition, a new TTV subtype, G2f, was found., Conclusion: The prevalence of TTV is high in healthy Chinese blood donors. Three main genotypes (G1, G2, and G3) were detected. In addition, a new TTV genotype, tentatively designated as G17, and a new subtype, G2f, were identified.

Background: In the current study the authors examined the pharmacokinetics of direct intralesional injection of cisplatin/epinephrine/bovine collagen gel in patients with hepatocellular carcinoma and cirrhosis., Methods: Six patients with cirrhosis and unresectable hepatocellular carcinoma received a direct intralesional injection (range, 6.7-26.7 mg) into their tumors under ultrasonographic guidance. The authors determined the total cisplatin (Pt) concentration in the plasma and urine and nonprotein-bound free Pt in plasma ultrafiltrate using flameless atomic absorption spectrometry. Data from individual patients were analyzed to calculate the pharmacokinetic parameters via a noncompartmental method for constant infusion. To demonstrate that the changes in pharmacokinetics are not related to the underlying cirrhosis, a similar methodology was applied to measure the pharmacokinetic parameters of four similar patients who were treated with cisplatin, 75 mg/m(2), as a 1-hour intravenous infusion., Results: The time to attain maximum concentration of total Pt after intralesional injection was dose-dependent and ranged from 2-13 hours. The concentration-time curve was biphasic in nature. The initial half-life of total Pt in patients who received an intralesional injection varied with the cisplatin dose. The initial half-life for cisplatin doses < 15 mg was approximately 9 hours and the initial half-life at higher cisplatin doses (> 15 mg) was approximately 25 hours. The area under the curve (AUC) was dose-dependent with values ranging from 38-150 microm/mL x hour. Pharmacokinetic parameters for free Pt (ultrafiltrate) were significantly different. The time to attain maximum concentration (t-max) and terminal half-life were shorter and the average AUC was approximately 100-fold lower than total Pt. After the intravenous infusion of cisplatin, the t-max for total and free Pt was 1.3 hours and 1.1 hours, respectively. The terminal half-life and average AUC for total Pt was 194 hours and 247 microg/mL per hour, respectively, and its corresponding parameters for free Pt after intravenous infusion were much lower, similar to the findings for the intralesional injection., Conclusions: The prolonged t-max and initial half-life noted with the intralesional injection of cisplatin/epinephrine/collagen gel are consistent with its proclaimed ability to retain cisplatin at the tumor and delay its release in systemic circulation. The kinetics of intralesional cisplatin injection also suggest local sequestration of the drug in the injected site. Parameters of intravenous cisplatin infusion in cirrhotic patients are similar to those of patients from the historic control group., (Copyright 2001 American Cancer Society.)