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The high oxygen electrocatalytic overpotential of flexible cathodes due to sluggish reaction kinetics result in low energy conversion efficiency of wearable zinc-air batteries (ZABs). Herein, lignin, as a 3D flexible carbon-rich macromolecule, is employed for partial replacement of polyacrylonitrile and constructing flexible freestanding air electrodes (FFAEs) with large amount of mesopores and multi-hollow channels via electrospinning combined with annealing strategy. The presence of lignin with disordered structure decreases the graphitization of carbon fibers, increases the structural defects, and optimizes the pore structure, facilitating the enhancement of electron-transfer kinetics. This unique structure effectively improves the accessibility of graphitic-N/pyridinic-N with oxygen reduction reaction (ORR) activity and pyridinic-N with oxygen evolution reaction (OER) activity for FFAEs, accelerating the mass transfer process of oxygen-active species. The resulting N-doped hollow carbon fiber films (NHCFs) exhibit superior bifunctional ORR/OER performance with a low potential difference of only 0.60 V. The rechargeable ZABs with NHCFs as metal-free cathodes possess a long-term cycling stability. Furthermore, the NHCFs can be used as FFAEs for flexible ZABs which have a high specific capacity and good cycling stability under different bending states. This work paves the way to design and produce highly active metal-free bifunctional FFAEs for electrochemical energy devices.
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Mangrove rhizosphere soils host diverse Actinobacteria tolerant to numerous stresses and are inevitably capable of exhibiting excellent biological activity by producing impressive numbers of bioactive natural products, including those with potential medicinal applications. In this study, we applied an integrated strategy of combining phylogenetic diversity, biological activities, and biosynthetic gene clusters (BGCs) screening approach to investigate the biotechnological importance of Actinobacteria isolated from mangrove rhizosphere soils from Hainan Island. The actinobacterial isolates were identifified using a combination of colony morphological characteristics and 16S rRNA gene sequence analysis. Based on the results of PCR-detected BGCs screening, type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected. Crude extracts of 87 representative isolates were subjected to antimicrobial evaluation by determining the minimum inhibitory concentration of each strain against six indicator microorganisms, anticancer activities were determined on human cancer cell lines HepG2, HeLa, and HCT-116 using an MTT colorimetric assay, and immunosuppressive activities against the proliferation of Con A-induced T murine splenic lymphocytes in vitro. A total of 287 actinobacterial isolates affiliated to 10 genera in eight families of six orders were isolated from five different mangrove rhizosphere soil samples, specififically, Streptomyces (68.29%) and Micromonospora (16.03%), of which 87 representative strains were selected for phylogenetic analysis. The crude extracts of 39 isolates (44.83%) showed antimicrobial activity against at least one of the six tested indicator pathogens, especially ethyl acetate extracts of A-30 (Streptomyces parvulus), which could inhibit the growth of six microbes with MIC values reaching 7.8 µg/mL against Staphylococcus aureus and its resistant strain, compared to the clinical antibiotic ciproflfloxacin. Furthermore, 79 crude extracts (90.80%) and 48 (55.17%) of the isolates displayed anticancer and immunosuppressive activities, respectively. Besides, four rare strains exhibited potent immunosuppressive activity against the proliferation of Con A-induced T murine splenic lymphocyte in vitro with an inhibition rate over 60% at 10 µg/mL. Type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected in 49.43, 66.67, and 88.51% of the 87 Actinobacteria, respectively. Signifificantly, these strains (26 isolates, 29.89%) harbored PKS I, PKS II, and NRPS genes in their genomes. Nevertheless, their bioactivity is independent of BGCs in this study. Our findings highlighted the antimicrobial, immunosuppressive, and anticancer potential of mangrove rhizosphere Actinobacteria from Hainan Island and the biosynthetic prospects of exploiting the corresponding bioactive natural product.
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Maintaining a steady affinity between gallium-based liquid metals (LM) and polymer binders, particularly under continuous mechanical deformation, such as extrusion-based 3D printing or plating/stripping of Zinc ion (Zn2+ ), is very challenging. Here, an LM-initialized polyacrylamide-hemicellulose/EGaIn microdroplets hydrogel is used as a multifunctional ink to 3D-print self-standing scaffolds and anode hosts for Zn-ion batteries. The LM microdroplets initiate acrylamide polymerization without additional initiators and cross-linkers, forming a double-covalent hydrogen-bonded network. The hydrogel acts as a framework for stress dissipation, enabling recovery from structural damage due to the cyclic plating/stripping of Zn2+ . The LM-microdroplet-initialized polymerization with hemicelluloses can facilitate the production of 3D printable inks for energy storage devices.
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Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Female , Aged , Male , Tissue Plasminogen Activator , Fibrinolytic Agents/therapeutic use , Stroke/drug therapy , Stroke/chemically induced , Ischemic Stroke/drug therapy , Brain Ischemia/drug therapy , Treatment OutcomeABSTRACT
An organic solvent-assisted catalyst-free mechanochemical reaction is developed to synthesize lithium hydride at mild gas pressures and room temperature. Studies show that the formation of intermediates on the surface of bulk lithium metal is crucial for the synthesis of high purity (>98%) LiH. This provides a new strategy for the large-scale production of lithium-based hydrogen storage materials.
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Single-atom catalysts (SACs) show great potential for rechargeable Zn-air batteries (ZABs); however, scalable production of SACs from sustainable resources is difficult owing to poor control of the local coordination environment. Herein, lignosulfonate, a by-product of the papermaking industry, is utilized as a multifunctional bioligand for the mass production of SACs with highly active MN4 S sites (M represents Fe, Cu, and Co) via strong metalnitrogen/sulfur coordination. This effectively adjusts the charge distribution and promotes the catalytic performance, leading to highly durable and excellent performance in oxygen reduction and evolution reactions for ZABs. This study paves the way for the industrial production of cost-effective SACs in a sustainable manner.
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Metal nanoparticles have attracted considerable scientific and technological interest in recent years, most related explorations and reports are focused on transition and noble metals. However, the synthesis and application of light metal nanoparticles represented by Mg have not been fully exploited, limited by their ultrahigh reactivity in air and preparation in harsh conditions. In this work, a simple and effective one-step organic solvent-assisted ball-milling process is developed to synthesize Mg and Li nanoparticles, which permits the formation of MgH2 in a hydrogen atmosphere in a one-step reaction process at ambient temperature. Further studies suggest that acetone chemisorbs on defects/surfaces of Mg during ball milling leading to the formation of a metastable magnesium complex, which significantly alters the physical and chemical characteristics of Mg grains. The formation of metastable complexes provides an attractive strategy to produce light metal nanoparticles and inspires the authors to study the interaction of organic solvents with light metals.
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Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.
Subject(s)
Ischemic Postconditioning , Ischemic Stroke , Aged , China , Female , Humans , Ischemic Postconditioning/methods , Ischemic Stroke/complications , Ischemic Stroke/therapy , Male , Middle Aged , Nervous System Diseases/etiology , Nervous System Diseases/prevention & control , Nervous System Diseases/therapy , Recovery of Function , Treatment Outcome , Upper Extremity/blood supplyABSTRACT
ABSTRACT: The goal of this work was to investigate the potential significance of neutrophil-lymphocyte ratio (NLR) in patients treated with maintenance hemodialysis (MHD).Herein, we retrospectively reviewed the electronic medical records of 100 patients with end-stage renal failure who were treated with MHD. All patients enrolled in this study met the inclusion criteria and were followed. The differences in each indicator between the two groups were compared using the Wilcoxon rank-sum test. On the other hand, Spearman correlation and logistic regression analysis were used to explore the correlation and risk factors for pulmonary infection between NLR and other indicators. Finally, we determined the optimal cut-off values for NLR, hypersensitive c-reactive protein (hs-CRP), and procalcitonin (PCT) diagnosis of pulmonary infection using the receiver operating characteristic curve.We found that NLR was positively correlated with age, PCT, hs-CRP, and hospital stay, but negatively correlated with hemoglobin, red blood cell, and Albumin. The expression levels of PCT, hs-CRP, and NLR in the infected group decreased significantly than those before treatment. Multiple regression analysis revealed that NLR is an important independent risk factor for MHD patients with pulmonary infection. Additionally, receiver operating characteristic curve analysis showed that the sensitivity, specificity, and area under the curve were 87.76%, 100%, and 0.920 when using NLR combined with hs-CRP to predict pulmonary infection in MHD patients, whereas that of NLR combined with PCT were 87.76%, 96.08%, and 0.944, respectively.Findings from this study suggested that NLR is an independent risk factor for MHD patients with pulmonary infection, which can effectively predict pulmonary infection. Moreover, sensitivity and specificity were greatly enhanced when using NLR combined with PCT/hs-CRP to predict pulmonary infection in MHD patients.
Subject(s)
Lymphocytes/classification , Neutrophils/classification , Pneumonia/etiology , Renal Dialysis/adverse effects , Adult , China , Female , Humans , Kidney Failure, Chronic/therapy , Leukocyte Count/methods , Leukocyte Count/statistics & numerical data , Male , Middle Aged , Pneumonia/blood , ROC Curve , Renal Dialysis/methods , Renal Dialysis/statistics & numerical data , Retrospective StudiesABSTRACT
Background: There is no doubt that thyroid dysfunction is associated with psychiatric disorders. A large amount of thyroid carcinoma patients displayed mood disorders after the withdrawal of levothyroxine (LT4). However, it is unclear whether the disorders are related to the transient withdrawal of LT4, and if yes, what the possible underlying mechanism is. This study aims to investigate the abnormal regional cerebral glucose metabolism (rCMRglu) in a group of papillary thyroid cancer (PTC) patients without LT4 for 4 weeks and prove the relationship between the abnormal rCMRglu with depression and anxiety. Methods: Brain 18F-FDG PET/CT data of 38 consecutive PTC patients with high/intermediate-risk from June 2016 to December 2017 have been analyzed. Of the 38 patients, 23 are in the LT4 withdrawal group (WG) and 15 in the LT4 replacement group (RG). These patients were also evaluated for depressive and anxiety symptoms within 24 h after the scans based on the Hamilton Depression Rating Scale (17 items, HRDS-17) and the Hamilton Anxiety Rating Scale (HAMA) respectively. Results: Thirty-eight patients (12 men, 26 women; age range, 25-69 years; mean age, 45.8 years) were selected in the study. Compared with the RG, patients in WG showed depression and anxiety with higher total scores of HRDS-17 and HAMA (14.7 ± 5.8 vs 3.8 ± 5.5, t = -5.74, p = 0.00; 9.3 ± 4.3 vs 2.7 ± 4.1, t = -4.74, p = 0.00, respectively). In the brain glucose metabolism analysis, the WG patients showed lower rCMRglu in Occipital_Mid_R and Postcentral_L. On the other hand, data illustrated significant rCMRglu increases in the Frontal_Sup_Orb_L. Compared with the healthy group (HG), the rCMRglu of the Postcentral_L and Precuneus_L showed hypoactivity, but the Hippocampus_R and the Temporal_Inf_L showed hyperactivity. This analysis yielded a significant correlation between abnormal rCMRglu with the free thyroxine level, the serum thyroid-stimulating hormone level, HRDS-17, and HAMA scores. Conclusions: The findings showed that more PTC patients exhibited depression and anxiety after LT4 withdrawal for 4 weeks. More attention should be paid to these hypothyroid patients while they were in the hospital. Such a short-term LT4 withdrawal also likely induced abnormal rCMRglu. Our study attempts to explain the possible mechanism of mood disorders related to transient hypothyroidism.
Subject(s)
Brain/drug effects , Glucose/metabolism , Thyroid Cancer, Papillary/drug therapy , Thyroid Cancer, Papillary/metabolism , Thyroxine/therapeutic use , Adult , Aged , Brain/diagnostic imaging , Brain/metabolism , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Positron Emission Tomography Computed Tomography , Retrospective Studies , Thyroid Cancer, Papillary/diagnostic imaging , Withholding TreatmentABSTRACT
The understanding concerning the function of immune system in cancer has achieved considerable advance with time passes by. Manipulating genetically engineered immune cells were investigated as a novel strategy for treating cancer. Chimeric antigen receptors (CARs) are recombinant protein molecules by merging the exquisite targeting the potent cytotoxicity of T cells and specificity of monoclonal antibodies and, which could trigger serial cascades of signal transduction and thereby activate T cells to directly destroy the tumor cells. Manufacturing CAR-modified T lymphocytes were successfully implemented in treating cancer derived from they could specifically retarget tumor-associated antigens, causing effective elimination of tumor cells, which spurred the optimization and development of new CAR-T cell technology. The advancement of synthetic biology methodologies of cell therapy in CAR-T would ultimately provide us with a much safer, reliable and efficient modality to against cancer. This review primarily described the emergence, development and application of cell therapy in CAR-T, then discuss the side effects and the potential factors of tumor reccurrence caused by CAR-T cell therapy, in addition to the corresponding countermeasure concerning complications.
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The latest statistics show that rates of morbidity and mortality for hepatocellular carcinoma are gradually increasing over time. Accumulating evidence indicates that circular RNAs (circRNAs) participate in the regulation of gene transcription and translation and exert a crucial role in endogenous RNA network. circRNAs are implicated in the pathogenesis of numerous tumors including hepatocellular carcinoma (HCC), gastric carcinoma and bladder cancer. Of note, the effect of circRNAs in HCC has drawn increasing public attention. Previous studies revealed that the function of circRNAs mainly consists of sponges of miRNA and RNA-binding proteins, alternative splicing of pre-mRNAs, transcriptional and translational regulators, and potential to encode proteins. In addition, recent research data indicate that the expression level of circRNAs is closely correlated with metastasis, invasion, and occurrence of HCC in patients. These findings imply that circRNAs may be useful as biomarkers for diagnosis and prediction of prognosis of HCC. In this review, we have systemically summarized current viewpoints regarding the role of circRNAs expression in HCC to provide an important reference illustrating the underlying mechanism of HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , RNA, Circular/physiology , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , MicroRNAs/metabolism , Neoplasm Invasiveness/genetics , Neoplasm Metastasis/genetics , Prognosis , RNA, Circular/metabolism , RNA-Binding Proteins/metabolismABSTRACT
Mechanically stable and foldable air cathodes with exceptional oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities are key components of wearable metal-air batteries. Herein, a directional freeze-casting and annealing approach is reported for the construction of a 3D honeycomb nanostructured, N,P-doped carbon aerogel incorporating in situ grown FeP/Fe2 O3 nanoparticles as the cathode in a flexible Zn-air battery (ZAB). The aqueous rechargeable Zn-air batteries assembled with this carbon aerogel exhibit a remarkable specific capacity of 648 mAh g-1 at a current density of 20 mA cm-2 with a good long-term durability, outperforming those assembled with commercial Pt/C+RuO2 catalyst. Furthermore, such a foldable carbon aerogel with directional channels can serve as a freestanding air cathode for flexible solid-state Zn-air batteries without the use of carbon paper/cloth and additives, giving a specific capacity of 676 mAh g-1 and an energy density of 517 Wh kg-1 at 5 mA cm-2 together with good cycling stability. This work offers a new strategy to design and synthesize highly effective bifunctional air cathodes to be applied in electrochemical energy devices.
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BACKGROUND: Chronic kidney disease (CKD) is a kidney disease in which there is gradual loss of kidney function over time and end-stage renal disease (ESRD) is the final stage of CKD. Both CKD and ESRD are worldwide health problems with a high economic cost to health systems. However, the molecular mechanisms of the development of CKD and ESRD remain poorly understood. This study aimed to systematically elucidate the molecular mechanisms of the development of CKD and ESRD. METHODS: Transcriptome data of CKD and ESRD were downloaded from the NCBI-GEO database. Differentially expressed genes between cases and controls (chronic kidney disease patients vs. controls, end-stage renal disease patients vs. controls) were calculated using the empirical Bayes algorithm. Gene set enrichment analysis (GSEA) was used for analyzing the KEGG pathway difference between cases and controls. Furthermore, CKD and ESRD target genes were obtained from the Thomson Reuters Integrity database. Tissue-specific gene interaction network analysis was performed using the GIANT web server. RESULTS: There were multiple damaged pathways in ESRD but only a few pathways were disturbed in CKD. Furthermore, we identified 9 dysregulated anti-ESRD genes but no dysregulated anti-CKD genes. Network analysis revealed that the NF-kB signaling pathway was essential for ESRD. CONCLUSIONS: This study revealed several crucial anti-ESRD genes that are involved in the regulation of the NF-kB signaling pathway. This information may be helpful for the treatment of ESRD.
Subject(s)
Kidney Failure, Chronic , Renal Insufficiency, Chronic , Bayes Theorem , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/genetics , Renal Insufficiency, Chronic/genetics , TranscriptomeABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world, with a high degree of malignancy and recurrence. The influence of the ceRNA network in tumor on the biological function of liver cancer is very important, It has been reported that many lncRNA play a key role in liver cancer development. In our study, integrated data analysis revealed potential eight novel lncRNA biomarkers in hepatocellular carcinoma. METHODS: Transcriptome data and clinical data were downloaded from the The Cancer Genome Atlas (TCGA) data portal. Weighted gene co-expression network analysis was performed to identify the expression pattern of genes in liver cancer. Then, the ceRNA network was constructed using transcriptome data. RESULTS: The integrated analysis of miRNA and RNAseq in the database show eight novel lncRNAs that may be involved in important biological pathways, including TNM and disease development in liver cancer. We performed function enrichment analysis of mRNAs affected by these lncRNAs. CONCLUSIONS: By identifying the ceRNA network and the lncRNAs that affect liver cancer, we showed that eight novel lncRNAs play an important role in the development and progress of liver cancer.
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BACKGROUND Worldwide, hepatocellular carcinoma (HCC) accounts for 80-90% of all cases of primary liver cancer, and is one of the ten most common malignancies. This study used bioinformatics analysis to identify genes associated with patient outcome in stages I-IV HCC and the gene pathways that distinguished between normal liver and liver cells and HCC and human HCC cell lines. MATERIAL AND METHODS Target genes were defined as those that had marketed drugs or drugs under development targeting a specific gene and acquired from the Clarivate Analytics Integrity Database. Differential expression gene analysis, co-expression network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, survival analysis and receiver operating characteristic (ROC) curve analysis were used to explore the similarities and differences in gene expression profiles, functional associations, and survival in stage I-IV HCC. Normal liver cells (HL-7702) and HCC cell lines (HepaRG, HepG2, SK-Hep1, and Huh7) were studied using Western blot and quantitative reverse transcription PCR (RT-qPCR). RESULTS Hierarchical gene clustering identified target genes that distinguished between HCC and normal liver tissue. For stages I-IV HCC, there were seven commonly upregulated target genes EPHB1, LTK, NTRK2, PTK7, TBK1, TIE1, and TLR3, which were mainly involved in immune and signaling transduction pathways. PTK7 was highly expressed in stage I-IV HCC and was an independent prognostic marker for reduced overall survival (OS). CONCLUSIONS Bioinformatics analysis, combined with patient survival analysis, identified PTK7 gene expression as a potential therapeutic target and prognostic biomarker for all stages of HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Cell Adhesion Molecules/genetics , Computational Biology/methods , Receptor Protein-Tyrosine Kinases/genetics , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/metabolism , Cell Adhesion Molecules/physiology , Cell Line, Tumor , China , Cluster Analysis , Databases, Genetic , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic/genetics , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Neoplasm Staging , Prognosis , Protein Interaction Maps/genetics , ROC Curve , Receptor Protein-Tyrosine Kinases/physiology , Transcriptome/geneticsABSTRACT
Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is influenced by sex and multiple metabolic abnormalities. The present study aimed to compare the overall metabolic changes between male and female HCC patients and identify key metabolic genes. Metabolic genes and pathways were identified based on analyses of publicly available data. Differential expression analysis, gene set enrichment analysis, survival analysis and transcriptional regulation analysis were employed to explore sex differences and identify key metabolic genes in HCC. The results suggested that female patients had more severe metabolic gene expression abnormalities and pathway deregulation than male patients. This study identified 9 key metabolic genes, and only upregulated ALDH1A2 independently increased overall survival risk in patients. Bioinformatic analyses suggest that upregulated GATA3 and TAL1 activate ALDH1A2 and then disrupt amino acid and carbohydrate metabolism, which may increase the risk of HCC. This study identified a novel contribution of upregulated ALDH1A2 to HCC. Future studies are needed to elucidate the potential metabolic mechanism of the role of ALDH1A2 in HCC.
Subject(s)
Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Metabolic Networks and Pathways/genetics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Male , Prognosis , Survival Analysis , Transcription Factors/metabolism , Transcription, GeneticABSTRACT
Townes-Brocks syndrome (TBS) is a rare autosomal dominant congenital anomaly syndrome characterized by the triad of anorectal, hand and external ear malformations. Kidney involvement is less common and may progress to end-stage renal failure (ESRF) early in life. The present study reports the case of a male patient presenting with multiple bilateral cortical kidney cysts at the age of 4 years, at which time the kidneys were of normal size and function. A clinical diagnosis of autosomal recessive polycystic kidney disease was made initially as the patient's parents are clinically healthy. However, the consideration of extra-renal involvements (imperforate anus at birth, preaxial polydactyly and dysplastic right ear) following the progression of the patient to ESRF at the age of 16 years, led to the diagnosis of TBS. This prompted sequencing of the SALL1 gene, which identified a novel heterozygous nonsense mutation in the mutational 'hotspot' of exon 2 (c.874C>T, p.Q292X), and this mutation was not detected in healthy controls. The current case highlights that TBS may present with normal sized, cystic kidneys in childhood, while recognition of extra-renal features of cystic kidney diseases, such as TBS, and genetic testing may facilitate the correct diagnosis and transmission mode. Reaching a correct diagnosis of as TBS is important since this condition has a 50% rate of transmission to offspring and can progress to ESRF early in life.
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PURPOSE: The aim of the study was to detect the expression of Sox10 in human nasopharyngeal carcinoma (NPC) and investigate the relationship between its expression and the clinicopathological characteristics of NPC patients. PATIENTS AND METHODS: Tumor specimens (n=105) were retrospectively collected from patients with NPC diagnosed between 2004 and 2005 who presented at Hunan Cancer Hospital. Immunohistochemistry analyses were performed to characterize the expression of Sox10 in NPC. Kaplan-Meier survival and Cox regression analyses were employed to evaluate the prognosis of 105 NPC patients. RESULTS: The results showed that Sox10 was markedly overexpressed in human NPC tissues. Analysis of clinicopathological parameters showed that high Sox10 expression was significantly correlated with the clinical stage (P=0.032), T classification (P=0.034), and lymph node metastasis (P=0.03). Cox regression analyses further showed that Sox10 expression was an independent prognostic factor for overall survival (P=0.005). This is the first time Sox10 has shown its importance in predicting NPC progressiveness and survival outcomes. CONCLUSION: Sox10 serves as a potential biomarker for NPC patients. It may hopefully become a novel therapeutic target for NPC patients.
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BACKGROUND: Quantitative evaluation of position control ability in stroke patients is needed. Here we report a demonstration of position control ability assessment and test-retest reliability during squat-stand activity on a new system in hemiparetic patients and controls. METHODS: Sixty-two healthy adults and thirty-four hemiparetics were enrolled. RESULTS: During partial weight support, the ICCs ranged from 0.77 to 0.91, which indicated a good reliability. During standard weight bearing and resistance, the ICCs varied from 0.64 to 0.86 and 0.54 to 0.84, respectively, indicating a fair reliability. Compared with the healthy adults, the stroke patients demonstrated poorer position control ability. CONCLUSIONS: The posturography of the squat-stand activity is a new and reliable measurement tool for position control. According to the methods proposed here, hemiparetics can be differentiated from healthy adults using the squat-stand activity. This activity will provide a new evaluation tool and therapy with visual feedback for the stroke patients. TRIAL REGISTRATION: Chinese clinical trial registry, ChiCTR-TRC-10000863.