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1.
Proc Natl Acad Sci U S A ; 121(24): e2311180121, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38830101

ABSTRACT

As a sustainable and promising approach of removing of nitrogen oxides (NOx), catalytic reduction of NOx with H2 is highly desirable with a precise understanding to the structure-activity relationship of supported catalysts. In particular, the dynamic evolution of support at microscopic scale may play a critical role in heterogeneous catalysis, however, identifying the in situ structural change of support under working condition with atomic precision and revealing its role in catalysis is still a grand challenge. Herein, we visually capture the surface lattice expansion of WO3-x support in Pt-WO3-x catalyst induced by NO in the exemplified reduction of NO with H2 using in situ transmission electron microscopy and first reveal its important role in enhancing catalysis. We find that NO can adsorb on the oxygen vacancy sites of WO3-x and favorably induce the reversible stretching of W-O-W bonds during the reaction, which can reduce the adsorption energy of NO on Pt4 centers and the energy barrier of the rate-determining step. The comprehensive studies reveal that lattice expansion of WO3-x support can tune the catalytic performance of Pt-WO3-x catalyst, leading to 20% catalytic activity enhancement for the exemplified reduction of NO with H2. This work reveals that the lattice expansion of defective support can tune and optimize the catalytic performance at the atomic scale.

2.
Surg Endosc ; 38(4): 1823-1834, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38302758

ABSTRACT

OBJECTIVES: Seroma represents the most prevalent postoperative complication following laparoscopic inguinal hernia repair, particularly in the case of large inguinoscrotal hernias. This randomized controlled trial was undertaken with the objective of assessing the effects of internal orifice narrowing achieved by suturing the divided distal hernia sac in laparoscopic repair of indirect inguinoscrotal hernias. METHODS: A total of 58 patients aged 18 years or older, were randomized into two groups: Group I, which underwent internal orifice narrowing, and Group II, which served as the control without narrowing. The study's primary endpoint was the incidence and volume of seroma in the inguinal region on postoperative days 1 and 7, as well as at 1, 3, and 6 months following the procedure. Secondary outcomes encompassed metrics like total operative time, acute and chronic pain levels, duration of hospital stay, recurrence rates, and the occurrence of any additional complications. RESULTS: In comparison to the control group, the experimental group exhibited a significantly lower incidence of seroma formation at 7 days (P = 0.001). Furthermore, the ultrasonic assessment indicated a reduced seroma volume in the operative group on postoperative day 7 (8.84 ± 17.71 vs. 52.39 ± 70.78 mL; P < 0.001). Acute pain levels and hospital stay were similar between the two groups (1.22 ± 0.76 vs. 1.04 ± 0.53, P = 0.073; 1.22 ± 0.07 vs. 1.19 ± 0.08, P = 0.627, respectively). Notably, neither chronic pain nor early recurrence, nor any other postoperative complications were observed in either group throughout the follow-up period, which extended for at least 6 months (range: 6-18 months). CONCLUSION: In the context of laparoscopic inguinoscrotal hernia repair, the incidence and volume of seroma can be significantly reduced through the implementation of internal orifice narrowing achieved by suturing the divided distal hernia sac. And, this reduction in seroma formation was not associated elevation in postoperative pain levels or recurrence rates.


Subject(s)
Chronic Pain , Hernia, Inguinal , Laparoscopy , Humans , Chronic Pain/surgery , Hernia, Inguinal/surgery , Hernia, Inguinal/complications , Herniorrhaphy/methods , Laparoscopy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Prospective Studies , Recurrence , Seroma/etiology , Seroma/prevention & control , Surgical Mesh/adverse effects , Double-Blind Method
3.
BMC Vet Res ; 20(1): 252, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851737

ABSTRACT

BACKGROUND: The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation. RESULTS: The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles. CONCLUSIONS: This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.


Subject(s)
Fasciola , Helminth Proteins , Insulin , Signal Transduction , Animals , Fasciola/genetics , Fasciola/metabolism , Insulin/metabolism , Helminth Proteins/metabolism , Helminth Proteins/genetics
4.
BMC Pediatr ; 24(1): 70, 2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38245707

ABSTRACT

BACKGROUND: Sleep disordered breathing (SDB) is broadly recognized to be associated with neurobehavioral deficits, which have significant impacts on developing-aged children and adolescents. Therefore, our study aimed to quantify the proportion of neurobehavioral impairments attributed to SDB in general children and adolescents by population attributable fraction (PAF). METHODS: The study was registered at PROSPERO (ID: CRD42023388143). We collected two types of literature on the prevalence of SDB and the risk of SDB-related neurobehavioral deficits from ten electronic databases and registers, respectively. The pooled effect sizes (Pe, Pc, RR) by random-effects meta-analysis were separately substituted into Levin's formula and Miettinen's formula to calculate PAFs. RESULTS: Three prevalence literature and 2 risk literature, all with moderate/high quality, were included in the quantitative analysis individually. The prevalence of SDB was 11% (95%CI 2%-20%) in children and adolescents (Pe), while the SDB prevalence was 25% (95%CI 7%-42%) in neurobehavioral patients (Pc). SDB diagnosis at baseline was probably associated with about threefold subsequent incidence of neurobehavioral deficits (pooled RR 3.24, 95%CI 1.25-8.41), after multi-adjustment for key confounders. Up to 19.8% or 17.3% of neurobehavioral consequences may be attributed to SDB from Levin's formula and Miettinen's formula, respectively. CONCLUSIONS: A certain number of neurobehavioral consequences may be attributable to SDB. It is essential for clinicians to identify and treat SDB timely, as well as screen for SDB in patients with neurobehavioral impairments. More longitudinal studies of SDB and neurobehavioral deficits are needed in the future to further certify the association between them.


Subject(s)
Sleep Apnea Syndromes , Adolescent , Child , Humans , Incidence , Prevalence , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/complications
5.
J Environ Manage ; 360: 121140, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38754190

ABSTRACT

Biochar preparation and application is an anticipated pathway for the resource utilization of biogas residue. In this study, biochars were prepared by the pyrolysis of biogas residue from food waste anaerobic digestion (named as BRBCs) under various pyrolysis temperatures (300, 500, 700, and 900 °C), and the effect of pyrolysis temperatures on the physicochemical characteristics of BRBCs was examined. The adsorption performance toward ciprofloxacin (CIP), a typical antibiotic in waterbodies, was also investigated. The results showed that pyrolysis temperature significantly changed the physicochemical properties of BRBCs. In addition, the minerals in the biogas residue, especially SiO2, were rearranged to form a mesoporous structure in biochar through a self-template strategy (without activator). BRBC prepared at 900 °C exhibited a high specific surface area and pore volume, well-developed mesopore structure, and more carbon structure defects, and exhibited the largest CIP adsorption capacity with 70.29 mg g-1, which was ascribed to the combined interaction of pore diffusion, π-π interactions, hydrogen bonding, complexation, and electrostatic forces. Furthermore, the adsorption of CIP by BRBC900 was well described by two-compartment kinetic and Langmuir isotherm models. BRBC900 showed good adsorption performance toward CIP at pH 7-9. The adsorption of CIP by BRBC is a spontaneous, exothermic, entropy-increasing process. Moreover, BRBC also presented a good recycling potential. Therefore, the preparation of mesoporous biochar based on a self-template strategy not only provides an option for the resource utilization of biogas residue but also offers a new option for the treatment of antibiotic wastewater.


Subject(s)
Biofuels , Charcoal , Ciprofloxacin , Pyrolysis , Ciprofloxacin/chemistry , Charcoal/chemistry , Biofuels/analysis , Adsorption , Water Pollutants, Chemical/chemistry , Temperature , Porosity , Kinetics
6.
Opt Express ; 31(22): 35777-35785, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-38017742

ABSTRACT

We experimentally investigated and demonstrated an ultralow noise hybrid amplifier that combines second-order distributed Raman amplifier (DRA) and first-order lumped Raman amplifier (LRA) in a cascaded approach. This approach allows for the reutilization of pump light from the LRA as the seed light in the second-order DRA, and simultaneous full-band dispersion compensation is realized by using dispersion compensation fiber in the LRA. This approach also supports broadband gain flattening based on the separated DRA and LRA configuration. The transmission application of the proposed amplifier was investigated using a set of 10 external cavity lasers (ECLs) in the C-band and 8 ECLs in the L-band. Ranging from 1531.12 nm to 1595.49 nm across C + L band, the proposed hybrid amplifier gives a maximum on-off gain of 27.2 dB and an average gain of 23.4 dB, with an extremely low effective noise figure (NF) of lower than -2.9 dB. Intensity modulation direct detection (IMDD) signal transmission is carried out at two different data rates across these 18 wavelengths in the C + L band: (1) 56 Gbps/λ PAM-4 signal; (2) 112 Gbps/λ PAM-4 signal. The results show that the error free transmissions are demonstrated over 101.6 km EX2000 fiber using both signals with 7% HD-FEC and 20% SD-FEC, respectively.

7.
Opt Lett ; 48(7): 1694-1697, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37221743

ABSTRACT

We report ultralow-noise transmission over a 102-km single-mode fiber using a purely nonlinear amplification scheme consisting of a second-order distributed Raman amplifier (DRA) and a phase-sensitive amplifier (PSA) based on periodically poled LiNbO3 waveguides. The hybrid DRA/PSA features a broadband gain over the C and L bands and an ultralow-noise advantage, with a less than -6.3 dB effective noise figure in the DRA stage and a 1.6 dB optical signal-to-noise ratio (OSNR) improvement in the PSA stage. Compared with the unamplified link, the OSNR is improved by 10.2 dB for a 20-Gbaud 16QAM signal in the C band, resulting in error-free detection (a bit-error rate of less than 3.8 × 10-3) for the signal with a low link input power of -25 dBm. Mitigation of nonlinear distortion is also achieved by the proposed nonlinear amplified system due to the subsequent PSA.

8.
Stem Cells ; 40(12): 1094-1106, 2022 12 31.
Article in English | MEDLINE | ID: mdl-36087098

ABSTRACT

Long noncoding RNAs (lncRNAs) emerge as important orchestrators of biological processes in embryonic stem cells (ESCs). LncRNA Lx8-SINE B2 was recently identified as an ESC-specific lncRNA that marks pluripotency. Here, we studied the function of lncRNA Lx8-SINE B2 in ESCs. Depletion of Lx8-SINE B2 disrupted ESC proliferation, repressed the expression of pluripotency genes, activated differentiation genes, and inhibited reprogramming to induced pluripotent stem cells. The reduction of the colony formation ability of ESCs upon Lx8-SINE B2 knockdown was accompanied by the elongation of the G1 phase and the shortening of the S phase. Transcriptome analysis revealed that Lx8-SINE B2 deficiency affected multiple metabolic pathways, particularly glycolysis. Mechanistically, Lx8-SINE B2 functions as a cytoplasmic lncRNA and interacts with the glycolytic enzyme Eno1 as shown by RNA pull-down and RNA localization analysis. Lx8-SINE B2 and Eno1 interact with and regulate each other's expression, hence promoting the expression of metabolic genes and influencing glycolysis. In conclusion, we have identified lncRNA Lx8-SINE B2 as a novel regulator of ESC proliferation, cell cycle, and metabolism through working with Eno1.


Subject(s)
Induced Pluripotent Stem Cells , RNA, Long Noncoding , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Embryonic Stem Cells/metabolism , Cell Differentiation/genetics , Gene Expression Profiling , Induced Pluripotent Stem Cells/metabolism
9.
Proc Natl Acad Sci U S A ; 117(5): 2519-2525, 2020 02 04.
Article in English | MEDLINE | ID: mdl-31964807

ABSTRACT

The highly conserved COP9 signalosome (CSN), composed of 8 subunits (Cops1 to Cops8), has been implicated in pluripotency maintenance of human embryonic stem cells (ESCs). Yet, the mechanism for the CSN to regulate pluripotency remains elusive. We previously showed that Cops2, independent of the CSN, is essential for the pluripotency maintenance of mouse ESCs. In this study, we set out to investigate how Cops5 and Cops8 regulate ESC differentiation and tried to establish Cops5 and Cops8 knockout (KO) ESC lines by CRISPR/Cas9. To our surprise, no Cops5 KO ESC clones were identified out of 127 clones, while three Cops8 KO ESC lines were established out of 70 clones. We then constructed an inducible Cops5 KO ESC line. Cops5 KO leads to decreased expression of the pluripotency marker Nanog, proliferation defect, G2/M cell-cycle arrest, and apoptosis of ESCs. Further analysis revealed dual roles of Cops5 in maintaining genomic stability of ESCs. On one hand, Cops5 suppresses the autophagic degradation of Mtch2 to direct cellular metabolism toward glycolysis and minimize reactive oxygen species (ROS) production, thereby reducing endogenous DNA damage. On the other hand, Cops5 is required for high DNA damage repair (DDR) activities in ESCs. Without Cops5, elevated ROS and reduced DDR activities lead to DNA damage accumulation in ESCs. Subsequently, p53 is activated to trigger G2/M arrest and apoptosis. Altogether, our studies reveal an essential role of Cops5 in maintaining genome integrity and self-renewal of ESCs by regulating cellular metabolism and DDR pathways.


Subject(s)
COP9 Signalosome Complex/metabolism , DNA Repair , Embryonic Stem Cells/enzymology , Genomic Instability , Peptide Hydrolases/metabolism , Animals , Apoptosis , COP9 Signalosome Complex/genetics , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Differentiation , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , G2 Phase Cell Cycle Checkpoints , Gene Knockout Techniques , Mice , Mitochondrial Membrane Transport Proteins/genetics , Mitochondrial Membrane Transport Proteins/metabolism , Oxidative Phosphorylation , Peptide Hydrolases/genetics , Reactive Oxygen Species/metabolism
10.
Biochem Genet ; 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38108937

ABSTRACT

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.

11.
Parasitol Res ; 123(1): 51, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38095703

ABSTRACT

In the present study, we reconstructed the transforming growth factor beta (TGF-ß) signaling pathway for Fasciola gigantica, which is a neglected tropical pathogen. We defined the components involved in the TGF-ß signaling pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (FgESP) was predicted via signal peptide annotation. The core components of the TGF-ß signaling pathway have been detected in F. gigantica; classical and nonclassical single transduction pathways were constructed. Four ligands have been detected, which may mediate the TGF-ß signaling pathway and BMP signaling pathway. Two ligand-binding type II receptors were detected, and inhibitory Smad7 was not detected. TLP, BMP-3, BMP-1, and ActRIb showed higher transcription in 42-day juvenile and 70-day juvenile, while ActRIIa, Smad1, ActRIIb, Smad8, KAT2B, and PP2A showed higher transcription in egg. TLM, Ski, Smad6, BMPRI, p70S6K, Smad2, Smad3, TgfßRI, Smad4, and p300 showed higher transcription in metacercariae. Four ligands, 2 receptors and 3 Smads are predicted to be present in the FgESP, suggesting their potential extrinsic function. This study should help to understand signal transduction in the TGF-ß signaling pathway in F. gigantica. In addition, this study helps to illustrate the complex mechanisms involved in developmental processes and F. gigantica - host interaction and paves the way for further characterization of the signaling pathway in trematodes.


Subject(s)
Fasciola , Animals , Fasciola/genetics , Fasciola/metabolism , Transforming Growth Factor beta/genetics , Signal Transduction
12.
Medicina (Kaunas) ; 59(2)2023 Feb 13.
Article in English | MEDLINE | ID: mdl-36837559

ABSTRACT

Background and Objectives: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are malignant disorders with adverse prognoses for advanced patients. Anoikis, which is involved in tumor metastasis, facilitates the survival and separation of tumor cells from their initial site. Unfortunately, it is rarely studied, and in the literature, studies have only addressed the prognosis character of anoikis for patients with CESC. Materials and Methods: We utilized anoikis-related genes (ANRGs) to construct a prognostic signature in CESC patients that were selected from the Genecards and Harmonizome portals. Furthermore, we revealed the underlying clinical value of this signature for clinical maneuvers by providing clinical specialists with an innovative nomogram on the basis of ANRGs. Finally, we investigated the immune microenvironment and drug sensitivity in different risk groups. Results: We screened six genes from fifty-eight anoikis-related differentially expressed genes in the TCGA-CESC cohort, and we constructed a prognostic signature. Then, we built a nomogram combined with CESC clinicopathological traits and risk scores, which demonstrated that this model may improve the prognosis of CESC patients in clinical therapy. Next, the prognostic risk scores were confirmed to be an independent prognostic indicator. Additionally, we programmed a series of analyses, which included immune infiltration analysis, therapy-related analysis, and GSVA enrichment analysis, to identify the functions and mechanisms of the prognostic models during the progression of cancer in CESC patients. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the six ANRGs. Conclusions: The present discovery verified that the predictive 6-anoikis-related gene (6-ANRG) signature and nomogram serve as imperative factors that might notably impact a CESC patient's prognosis, and they may be able to provide new clinical evidence to assume the role of underlying biological biomarkers and thus become indispensable indicators for prospective diagnoses and advancing therapy.


Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Neoplasms, Connective Tissue , Uterine Cervical Neoplasms , Female , Humans , Anoikis , Prognosis , Prospective Studies , Tumor Microenvironment
13.
Cancer Sci ; 113(12): 4120-4134, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36083239

ABSTRACT

The pro-inflammatory factor interleukin-8 (IL-8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin-8 enhanced HCC invasion by upregulating Snail and Twist1, whether this modulation relies on microRNAs (miR) is unclear. In this study, hsa-miR-370-3p was screened as candidate miRNA targeting Snail and Twist1, and its expression was downregulated by IL-8. Luciferase assays and RNA electrophoretic mobility shift assays were used to evaluate the interaction between miR-370-3p and targeted mRNAs. Coimmunoprecipitation, luciferase, and ChIP assays were undertaken to investigate the mechanisms underlying IL-8-mediated modification of miR-370-3p. Gain- and loss-of-function studies, Transwell assays, and a xenograft nude mouse model were used to investigate pro- and antitumor activities. Interleukin-8 and miR-370-3p levels were analyzed for clinical relevance in HCC patients. Our results showed that HCC patients with high levels of IL-8 experienced more metastasis and shorter survival. Interleukin-8 induced epithelial-mesenchymal transition and promoted liver cancer cell migration, invasion, and metastasis both in vitro and in vivo. MicroRNA-370-3p interacted with its cognate mRNA within the 3'-UTR regions of Twist1 and Snail mRNA directly and specifically and attenuated IL-8 protumoral effects on liver cancer cells. Interleukin-8 negatively modulated miR-370-3p through signal transducer and activator of transcription 3 (STAT3) activation by recruiting histone deacetylase 1 (HDAC1) to miR-370-3p promoter. The STAT3 and HDAC antagonists inhibited liver cancer cell migration and invasion. Patients with high miR-370-3p and low IL-8 levels had longer overall survival. In conclusion, our study elucidated a novel axis IL-8/STAT3/miR-370-3p/Twist1 and Snail relying on HDAC1 recruitment, which showed both diagnostic and therapeutic potentials of miR-370-3p in HCC metastasis.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Animals , Humans , Mice , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Interleukin-8/genetics , Interleukin-8/metabolism , Liver Neoplasms/pathology , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , RNA, Messenger , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Twist-Related Protein 1/genetics , Twist-Related Protein 1/metabolism , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolism
14.
BMC Cancer ; 22(1): 556, 2022 May 17.
Article in English | MEDLINE | ID: mdl-35581573

ABSTRACT

BACKGROUND: The bifunctional methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) has been reported to play an oncogenic role in various types of cancers. However, the function of MTHFD2 in urothelial carcinomas of bladder (UCB) and its association with tumor immune infiltration remains unknown. We aim to examine the suitability of MTHFD2 to be a novel biomarker of bladder cancer and whether MTHFD2 is linked to immune infiltration. METHODS: RNA sequencing data and clinical information (bladder cancer samples: normal samples = 414: 19) were downloaded from The Cancer Genome Atlas official website. Western blot analysis was performed to detect MTHFD2 expression in human bladder cancer (BLCA) cells and normal urothelial cell line SV-HUC-1. Associations between MTHFD2 expression and clinicopathological features were analyzed using Mann Whitney U test or Kruskal-Wallis H test. The "survival" and "survminer" packages were utilized to plot Kaplan-Meier survival curves. Moreover, the gene set enrichment analysis (GSEA) was conducted using a clusterProfiler package. The correlation of MTHFD2 expression with immune infiltration level was estimated using the single sample GSEA (ssGSEA) algorithm. Furthermore, associations between MTHFD2 and immune checkpoint genes were evaluated using the correlation analysis. RESULTS: Transcriptome analysis manifested that MTHFD2 was highly expressed in UCB tissues than normal bladder tissues, which was further confirmed by western blot analysis in human BLCA cells and SV-HUC-1 cells. Moreover, MTHFD2 high expression was significantly associated with the advanced disease progression. Also, the high expression of MTHFD2 was correlated with poor prognosis, and MTHFD2 was considered as an independent prognostic factor for disease specific survival. Furthermore, a number of cancer-related pathways were enriched in MTHFD2 high group, including NF-κB activation, JAK/STAT, and cancer immunotherapy by PD1 blockade. Several immune checkpoint molecules were also strongly associated with MTHFD2 expression, including PDCD1, CD274, CTLA4, CD276, LAG3, HAVCR2, and TIGIT. CONCLUSIONS: MTHFD2 expression was remarkably elevated in UCB, suggesting that MTHFD2 could be a promising biomarker for BLCA as well as novel target for anti-cancer immunotherapy since its close association with immune infiltration.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , B7 Antigens , Carcinoma, Transitional Cell/genetics , Humans , Oncogenes , Prognosis , Urinary Bladder
15.
Analyst ; 147(4): 597-603, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35040828

ABSTRACT

A "hotspot"-rich Ag-nanoparticle-decorated three-dimensional polymer substrate was fabricated, exhibiting an excellent surface-enhanced Raman scattering (SERS) activity. 4-Mercaptobenzoic acid (MBA) was selected as a probe molecule for comparing the SERS activity on selected substrates. The proposed detection chip with the adsorption of tetramethylthiuram disulfide (TTD) shows an excellent sensitivity for the quantitative determination of TTD and mercury ions (Hg2+). This chip exhibited a high sensitivity for the trace detection of the targets. Interestingly, we found that the adsorbed TTD is selectively sensitive to Hg2+. The SERS band had a significant frequency shift of 11 cm-1 as the concentration of Hg2+ increased from 10-10 to 10-3 mol L-1. More importantly, the frequency shift of the SERS band exhibited an excellent linear relationship with the concentration of Hg2+, and the determination limit for Hg2+ was 10-10 mol L-1. Furthermore, the proposed detection chip shows great application potential for the determination of pesticides and Hg2+.


Subject(s)
Mercury , Metal Nanoparticles , Polymers , Spectrum Analysis, Raman , Thiram
16.
RNA Biol ; 19(1): 866-876, 2022 01.
Article in English | MEDLINE | ID: mdl-35762570

ABSTRACT

RNA translation is the rate-limiting step when cells synthesize proteins. Elevating translation efficiency (TE) is intuitively beneficial. Particularly, when viruses invade host cells, how to compete with endogenous RNAs for efficient translation is a major issue to be resolved. We collected millions of worldwide SARS-CoV-2 sequences during the past year and traced the dynamics of allele frequency of every mutation. We defined adaptive and deleterious mutations according to the rise and fall of their frequencies along time. For 5'UTR and synonymous mutations in SARS-CoV-2, the selection on TE is evident near start codons. Adaptive mutations generally decrease GC content while deleterious mutations increase GC content. This trend fades away with increasing distance to start codons. Mutations decreasing GC content near start codons would unravel the complex RNA structure and facilitate translation initiation, which are beneficial to SARS-CoV-2, and vice versa. During this evolutionary arms race between human and virus, SARS-CoV-2 tries to improve its cis elements to compete with host RNAs for rapid translation.


Subject(s)
Evolution, Molecular , RNA, Viral , SARS-CoV-2 , Selection, Genetic , 5' Untranslated Regions , COVID-19/virology , Codon, Initiator , Humans , Mutation , RNA, Viral/genetics , SARS-CoV-2/genetics
17.
Nucleic Acids Res ; 48(18): 10211-10225, 2020 10 09.
Article in English | MEDLINE | ID: mdl-32894293

ABSTRACT

Endogenous retroviruses (ERVs) were usually silenced by various histone modifications on histone H3 variants and respective histone chaperones in embryonic stem cells (ESCs). However, it is still unknown whether chaperones of other histones could repress ERVs. Here, we show that H2A/H2B histone chaperone FACT plays a critical role in silencing ERVs and ERV-derived cryptic promoters in ESCs. Loss of FACT component Ssrp1 activated MERVL whereas the re-introduction of Ssrp1 rescued the phenotype. Additionally, Ssrp1 interacted with MERVL and suppressed cryptic transcription of MERVL-fused genes. Remarkably, Ssrp1 interacted with and recruited H2B deubiquitinase Usp7 to Ssrp1 target genes. Suppression of Usp7 caused similar phenotypes as loss of Ssrp1. Furthermore, Usp7 acted by deubiquitinating H2Bub and thereby repressed the expression of MERVL-fused genes. Taken together, our study uncovers a unique mechanism by which FACT complex silences ERVs and ERV-derived cryptic promoters in ESCs.


Subject(s)
DNA-Binding Proteins/physiology , Endogenous Retroviruses/genetics , High Mobility Group Proteins/physiology , Histone Chaperones/physiology , Promoter Regions, Genetic , Transcription Factors/physiology , Animals , Cell Line , Gene Expression Regulation , Histones/metabolism , Mice , Mouse Embryonic Stem Cells , Ubiquitin-Specific Peptidase 7/physiology
18.
Parasitol Res ; 121(6): 1709-1718, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35416490

ABSTRACT

Buffaloes, as highly susceptible definitive hosts of Fasciola gigantica, suffer from a high infection rate of fasciolosis, which causes enormous economic losses. Repeat infection is responsible for this high rate; thus, elucidating the protective immunity mechanism in repeat infection is decisive in fasciolosis prevention. Herein, a secondary experimental infection model was established to preliminarily reveal the protective immunity that occurs in repeat infection. In brief, animals were assigned to three groups: group A (uninfected control), group B (primary infection) and group C (secondary infection). Buffaloes were autopsied 20 weeks post-infection for measurements of the recovered flukes and hepatic examination. In addition, the detection of specific antibody (IgG) responses to F. gigantica excretory-secretory product (FgESP) throughout the whole period and weight gain throughout the first 4 months as a percentage (%) of the starting weight were also determined. The serum hepatic enzyme gamma glutathione transferase (GGT) levels were monitored to assess hepatic damage throughout the study period. Infection establishment was compared between group B and group C. Similar specific IgG patterns were observed between group B and group C, and hepatic damage was more severe in group C than group B. Significant differences in weight gain as a percentage of the start weight were observed between group A and group B at the 3rd and 4th months postprimary infection, while significant differences were not observed between group A and group C or group B and group C. Our results suggest that challenge infection cannot induce resistance against F. gigantica in buffaloes, which is consistent with the protective immunity against Fasciola hepatica reinfection observed in sheep and goats.


Subject(s)
Bison , Fasciola , Fascioliasis , Sheep Diseases , Animals , Antibodies, Helminth , Buffaloes , Fascioliasis/veterinary , Immunoglobulin G , Sheep , Weight Gain
19.
Nano Lett ; 21(1): 492-499, 2021 Jan 13.
Article in English | MEDLINE | ID: mdl-33258608

ABSTRACT

Developing low-cost and efficient electrocatalysts to accelerate oxygen evolution reaction (OER) kinetics is vital for water and carbon-dioxide electrolyzers. The fastest-known water oxidation catalyst, Ni(Fe)OxHy, usually produced through an electrochemical reconstruction of precatalysts under alkaline condition, has received substantial attention. However, the reconstruction in the reported catalysts usually leads to a limited active layer and poorly controlled Fe-activated sites. Here, we demonstrate a new electrochemistry-driven F-enabled surface-reconstruction strategy for converting the ultrathin NiFeOxFy nanosheets into an Fe-enriched Ni(Fe)OxHy phase. The activated electrocatalyst shows a low OER overpotential of 218 ± 5 mV at 10 mA cm-2 and a low Tafel slope of 31 ± 4 mV dec-1, which is among the best for NiFe-based OER electrocatalysts. Such superior performance is caused by the effective formation of the Fe-enriched Ni(Fe)OxHy active-phase that is identified by operando Raman spectroscopy and the substantially improved surface wettability and gas-bubble-releasing behavior.

20.
J Obstet Gynaecol ; 42(3): 379-384, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34030603

ABSTRACT

We compared complications in pregnancies that had Kielland's rotational forceps delivery (KRFD) with non-rotational forceps delivery (NRFD). Maternal outcomes included post-partum haemorrhage (PPH) and obstetric anal sphincter injury (OASIS); neonatal outcomes included admission to neonatal intensive care unit (NICU), 5-minute Apgar scores <7, hypoxic ischaemic encephalopathy (HIE), jaundice, shoulder dystocia and birth trauma. The study population included 491 (2.1%) requiring KRFD, 1,257 (5.3%) requiring NRFD and 22,111 (93.0%) that had SVD. In pregnancies with NRFD compared to KRFD, there was higher incidence of OASIS (8.5% vs. 4.7%; p = .006) and a non-significant increased trend for PPH (15.0% vs. 12.4%; p = .173). There was no significant difference in rates of admission to NICU (p = .628), 5-minute Apgar score <7 (p = .375), HIE (p = .532), jaundice (p = .809), severe shoulder dystocia (p = .507) or birth trauma (p = .514). Our study demonstrates that KRFD has lower rates of maternal complications compared to NRFD whilst the rates of neonatal complications are similar.IMPACT STATEMENTWhat is already known on this subject? Kielland's rotational forceps is used for achieving vaginal delivery in pregnancies with failure to progress in second stage of labour secondary to fetal malposition. The use of Kielland's forceps has significantly declined in the last few decades due to concerns about an increased risk of maternal and neonatal complications, despite the absence of any major studies demonstrating this increased risk.What do the results of this study add? There are some studies which compare the risks in pregnancies delivering by Kiellands forceps with rotational ventouse deliveries but there is limited evidence comparing the risks of rotational with non-rotational forceps deliveries. Our study compares the major maternal and neonatal complications in a large cohort of pregnancies undergoing rotational vs. non-rotational forceps deliveries.What are the implications of these findings for clinical practice and/or further research? The results of our study demonstrate that maternal and neonatal complications in pregnancies delivering by Kielland's rotational forceps undertaken by appropriately trained obstetricians are either lower or similar to those delivering by non-rotational forceps. Consideration should be given to ensure that there is appropriate training provided to obstetricians to acquire skills in using Kielland's forceps.


Subject(s)
Birth Injuries , Obstetric Labor Complications , Birth Injuries/epidemiology , Birth Injuries/etiology , Delivery, Obstetric/adverse effects , Extraction, Obstetrical/adverse effects , Female , Humans , Infant, Newborn , Obstetric Labor Complications/etiology , Obstetrical Forceps/adverse effects , Pregnancy
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