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INTRODUCTION: Increasing evidence reveals critical roles for CHD2 in children with developmental and epileptic encephalopathy. OBJECTIVES: The aim was to present clinical analysis results of five cases with CHD2 mutations and 157 reported cases with non-copy number variations (non-CNV) of CHD2. METHODS: This study recruited pediatric epilepsy patients with CHD2 mutations and clinical data from November 2016 to October 2023 in the Linyi People's Hospital, China. Whole-exome and gene panel sequencing were employed to find mutations. The HGMD and PubMed databases were examined for documented cases that had CHD2 mutations. RESULTS: This study reports five cases with CHD2 mutations: c.3543T > A, c.1850A > G, c.2536C > T, c.4233_4236del, c.3782G > C. Three novel mutations (c.3543T > A, c.1850A > G, c.2536C > T) have never been reported. c.4233_4236del has been reported in three cases, indicating that this locus may be a mutation hotspot. c.3782G > C has been reported in one case. All five patients had seizures before the age of four. Three patients had varying degrees of developmental delay, and four patients had varying degrees of intellectual disability. All of them had controlled seizures after Valproic acid (VPA) monotherapy or VPA in combination with other medications. Furthermore, we reviewed 157 reported cases having non-CNV mutations of CHD2. Most mutations of these cases were de novo. Epilepsy, developmental delay, and intellectual disability were the typical clinical phenotypes. We also found a significant clustering of the mutations near the C-terminus of the CHD2 protein (P < 0.001). CONCLUSION: This study reports new CHD2 genotypes and analyzes reported CHD2 mutation cases. Given its significance in epileptic encephalopathies, research on the CHD2 gene may provide new insights into epileptogenesis.
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BACKGROUND: Autogenous arteriovenous fistula (AVF) is the preferred vascular access mode. However, the earliest possible time for AVF puncture and whether premature puncture affects the AVF patency rate remain unclear. METHODS: In this multicenter retrospective cohort study, adult uremic patients who underwent AVF surgery for the first time at Taizhou Hospital or Enze Hospital of Zhejiang Province between September 1, 2018 and August 31, 2021 were enrolled. All patients were followed up for 1 year after puncture, and the status of fistula establishment and puncture, subsequent patency, loss to follow-up, renal transplantation, conversion to peritoneal dialysis, abandonment of the fistula, and death, were recorded. RESULTS: A total of 465 patients with AVFs were included in this study, including 59 (12.7%) patients with fistulas that were cannulated within 30 days. In the early puncture group, the levels of serum creatinine and urea nitrogen were higher, while the levels of hemoglobin and albumin were lower, suggesting that these patients needed urgent dialysis. Furthermore, the rate of non-cuffed catheter use was higher, while the rate of cuffed catheter use was lower, and femoral vein puncture was preferred over internal jugular vein puncture. The mean duration of catheter indwelling was shorter in the early puncture group (19 vs 70 days, p < 0.001). The estimated AVF primary and cumulative functional patency at 12 months was 81.1% versus 82.3% and 98.3% versus 98.7% in the early puncture and control groups, respectively. Kaplan-Meier analysis revealed no significant difference in AVF primary and cumulative functional patency between the two groups. CONCLUSIONS: In patients with an established fistula in urgent need of hemodialysis, to avoid new catheterization, a puncture can be performed within 30 days in those with well-developed blood vessels after adequate ultrasound and clinical evaluation without affecting the patency of the fistula.
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To produce functional protective textiles with minimal environmental footprints, we developed durable superhydrophobic antimicrobial textiles. These textiles are characterized by a micro-pleated structure on polyester fiber surfaces, achieved through a novel plasma impregnation crosslinking process. This process involved the use of water as the dispersion medium, water-soluble nanosilver monomers for antimicrobial efficacy, fluorine-free polydimethylsiloxane (PDMS) for hydrophobicity, and polyester (PET) fabric as the base material. The altered surface properties of these fabrics were extensively analyzed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS), thermogravimetric analysis (TGA), and water contact angle (WCA) measurements. The antimicrobial performance of the strains was evaluated using Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. After treatment, the fabrics exhibited enhanced hydrophobic and antimicrobial properties, which was attributed to the presence of a micro-pleated structure and nanosilver. The modified textiles demonstrated a static WCA of approximately 154° and an impressive 99.99% inhibition rate against both test microbes. Notably, the WCA remained above 140° even after 500 washing cycles or 3000 friction cycles.
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Antiinfecciosos , Poliésteres , Plata , Poliésteres/química , Textiles , Antiinfecciosos/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Agua/químicaRESUMEN
PURPOSE: Seizure threshold 2 protein homolog gene (SZT2, MIM: 615463) related diseases are extremely rare autosomal recessive disorders with a wide spectrum of clinical phenotypes ranging from mild intellectual impairment to severe developmental epileptic encephalopathy (DEE). Most SZT2 related diseases are accompanied by craniofacial malformation and corpus callosum malformation. This study attempts to analyze and summarize the clinical phenotype and genetic characteristics of SZT2 related diseases, providing a basis for early diagnosis, treatment, and prognosis. METHOD: We analyzed the clinical characteristics of a Chinese child with pathogenic variants of SZT2. We also performed whole-exome sequencing (WES) on the patient. In addition, we conducted a literature review of previously reported patients with pathogenic mutations in the SZT2 gene. RESULT: The proband was a boy aged 1 year and 9 months with severe global developmental delay, transient drug-controlled focal epilepsy, cluster epilepsy, autism spectrum disorder, craniofacial deformity, hypotonia, focal EEG discharge, corpus callosum malformation, and persistent cavum septum pellucidum. WES revealed that the patient carried the SZT2 gene c.7584dupA and c.6302A>C complex heterozygous variants; the former being Likely Pathogenic (LP) and the latter Uncertain Significance (VUS) according to ACMG classification guidelines. According to our literature review, 43 cases of SZT2 related diseases have been reported so far; these include 15 cases with homozygous variations and 28 cases with complex heterozygous variations. A total of 57 types of variation were found, including 47 genetic variants, 2 de novo variants, and 8 unknown genetic modes. In addition, 2 high-frequency variants were found (c.5949_5951delTGT and c.6553C>T). The main clinical manifestations of the 40 patients were global developmental delay (GDD) of varying degrees (38/40, 95.00 %), seizures (36/40, 90.00 %), cranial deformity (27/40, 67.50 %), facial deformity (22/40, 55.00 %), hypotonia (22/40, 55.00 %), abnormal interseizure EEG discharge (26/40, 65.00 %), slow background activity (20/40, 50.00 %), corpus callosum deformity (18/40, 45.00 %). There was also one case of sudden unexpected death in epilepsy (SUDEP) and 3 cases of death from infection. In addition, three fetuses with the same variant had hydrocephalus and encephalocele. CONCLUSION: The compound heterozygous mutation of c.7584dupA and c.6302A>C in the SZT2 gene is the genetic etiology of this patient, expanding the mutation spectrum of SZT2 related diseases. Early genetic testing is the best choice for clear diagnosis, treatment, and prognosis.
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Trastorno del Espectro Autista , Epilepsia , Malformaciones del Sistema Nervioso , Niño , Masculino , Humanos , Agenesia del Cuerpo Calloso/complicaciones , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/complicaciones , Hipotonía Muscular/complicaciones , Epilepsia/complicaciones , Malformaciones del Sistema Nervioso/complicaciones , Fenotipo , Proteínas del Tejido Nervioso/genéticaRESUMEN
Background: Small cell lung cancer (SCLC) is a common subtype of lung cancer, and there is currently no established method for the early identification of SCLC. We prepared a novel rare-earth near-infrared (NIR) downconversion nanoprobe to identify SCLC cells. Methods: The shell precursors Gd-OA and Na-TFA-OA were prepared, and the NaYF4:Nd@NaGdF4-ProGRP antibody probe was obtained after synthesizing downconversion fluorescent nanocrystals. The probe was used for NIR identification of cancer cells and subcutaneous tumors in nude mice. The biotoxicity of the probe to SCLC cells and nude mice was studied. Results: The NaYF4:Nd@NaGdF4-ProGRP antibody probe was successfully prepared, with a size of 44 nm, an NIR emission peak at approximately 1060 nm, and a concentration of 40 µmol/mL. The probe could achieve accurate NIR identification of SCLC cells and subcutaneous tumors in nude mice. Optimal images of the subcutaneous tumor model were obtained approximately 10 minutes after probe injection. There was no significant change in the hematology indices, respiratory rate, or heart rate of nude mice after the probe was injected (all P > 0.05). Conclusion: We have successfully prepared a low-toxicity probe that can identify SCLC cells, which may be useful for the early detection of SCLC. And conduct theoretical exploration for non-invasive identification and identification of some early metastatic lesions without pathological sampling in the future.
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Neoplasias Pulmonares , Nanopartículas , Carcinoma Pulmonar de Células Pequeñas , Ratones , Animales , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Ratones Desnudos , Nanopartículas/toxicidad , Nanopartículas/químicaRESUMEN
Lung cancer has been the leading cause of cancer-related deaths worldwide for decades. Despite the increasing understanding of the underlying disease mechanisms, the prognosis still remains poor for many patients. Novel adjuvant therapies have emerged as a promising treatment method to augment conventional methods and boost the therapeutic effects of primary therapies. Adjuvant therapy based on nanomedicine has gained considerable interest for supporting and enhancing traditional therapies, such as chemotherapy, immunotherapy, and radiotherapy, due to the tunable physicochemical features and ease of synthetic design of nanomaterials. In addition, nanomedicine can provide protective effects against other therapies by reducing adverse side effects through precise disease targeting. Therefore, nanomedicine-based adjuvant therapies have been extensively employed in a wide range of preclinical and clinical cancer treatments to overcome the drawbacks of conventional therapies. In this review, we mainly discuss the recent advances in adjuvant nanomedicine for lung cancer treatment and highlight their functions in improving the therapeutic outcome of other therapies, which may inspire new ideas for advanced lung cancer therapies and stimulate research efforts around this topic.
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Neoplasias Pulmonares , Nanoestructuras , Neoplasias , Humanos , Nanomedicina , Neoplasias Pulmonares/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Terapia Combinada , Neoplasias/tratamiento farmacológicoRESUMEN
Background: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is considered a key negative regulator in T-cell-mediated response. However, few studies have been reported on the relationship between TIM-3 expression in tumor-associated macrophages (TAMs) and clinicopathological characteristics of patients. This study evaluated the correlation between the expression of TIM-3 on the surface of TAMs macrophages in tumor matrix and the clinical outcome of patients with non-small cell lung cancer (NSCLC). Methods: The expression of CD68, CD163 and TIM-3 in 248 NSCLC patients who underwent surgery in Zhoushan Hospital from January 2010 to January 2013 was detected by immunohistochemistry (IHC). From the date of operation to the date of death, overall survival (OS) was measured to analyze the relationship between the expression of Tim-3 and the prognosis of NSCLC patients. Results: The study assessed 248 patients with NSCLC. TIM-3 expression in TAMs was more frequently identified in patients with higher carcinoembryonic antigen (CEA) levels, lymph node metastasis, higher grade, high CD68 expression, and high CD163 expression (P<0.05). The OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups (P=0.01). Patients with high TIM-3 and CD68/CD163 expressions had the worst prognosis, whereas patients with low expressions of both TIM-3 and CD68/CD163 had the best prognosis (P<0.05). In NSCLC, the OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups (P=0.01). In lung adenocarcinoma, the OS of the high TIM-3 expression groups was shorter than that of the low TIM-3 expression groups(P=0.03). Conclusions: TIM-3 expression in TAMs may be a promising prognostic biomarker for NSCLC or adenocarcinoma. Our results demonstrated that high TIM-3 expression in TAMs was an independent predictor of worse prognosis in patients.
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BACKGROUND: Pathogenic variants of ATP1A2 (OMIM ID: 182340) are usually associated with familial hemiplegic migraine type 2 (FHM-2), alternating hemiplegia of childhood (AHC), early infantile epileptic encephalopathy (EIEE), transient cytotoxic edema, and so on. Here, we present a novel heterozygous ATP1A2 variant in a girl with alternating hemiplegia, febrile seizures, developmental delay (which subsequently subsided), and MELAS-like syndrome (as indicated by brain MRI). The patient did not experience migraine with aura. METHODS: The patient was an 8-year-old girl with normal growth and development. Beginning from the age of 3 years and 8 months, the patient experienced several episodes of alternating limb paralysis. The episodes were accompanied by the appearance of MELAS-like findings on brain MRI, which corresponded to the hemiplegia. There were abnormal linear signals in the cerebral cortex on the opposite side of the hemiplegic limb. Each time the patient recovered from hemiplegia, and each time MRI showed no lesions remained after recovery. No obvious abnormality was found in other examinations. Finally, the patient underwent whole-exome sequencing (WES). RESULTS: WES revealed a novel and de novo heterozygous variant in the ATP1A2 (NM_000702.3) c.335C>A:p.Ala112Asp (not previously reported). We examined the variant position in the 3D protein structure and found that a missense mutation at this site is a nonconservative substitution. The variation is nonpolymorphic. It occurs at a very low frequency in the population, and its ACMG classification is likely pathogenic. CONCLUSION: At present, there are limited reports of mutations in the ATP1A2 gene causing AHC. This is the first case of brain MRI showing MELAS-like imaging in an AHC patient, and more cases are needed for verification. Early genetic testing and family screening can aid in the diagnosis and treatment of genetic diseases. The relationship between ATP1A2 gene mutation genotype and clinical phenotype needs to be further studied.
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Hemiplejía , Síndrome MELAS , Humanos , Pueblos del Este de Asia , Hemiplejía/genética , Síndrome MELAS/genética , ATPasa Intercambiadora de Sodio-Potasio/genética , Femenino , NiñoRESUMEN
"Core sliding" in metal nanoclusters drives the reconstruction of external structural units and provides an ideal platform for mapping their precise transformation mechanism and evolution pathway. However, observing the movement behavior of metal atoms in experiments is still challenging because of the uncertain stability of intermediates. In this work, a series of Au-Cd alloy nanoclusters with continuously assembled kernels (one icosahedral building block assembled with 0 to 3 tetrahedral units) were constructed. As the assembly continued, it eventually led to the Cd atom doping into the inner positions of the clusters. Importantly, the Cd doped into the interior of the cluster exhibits a different behavior than the surface or external Cd atoms (dispersion doping vs localized occupy), which provides experimental evidence of the sliding behavior in the nanocluster kernel. Furthermore, density functional theory (DFT) calculations reveal that this sliding behavior in the inner sites of nanoclusters is an energetically favorable process. In addition, these Au-Cd nanoclusters exhibit tunable optical properties with different assembly patterns in their kernels.
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Mitochondrial function and homeostasis are critical to the proliferation of lung cancer cells. T-cell immunoglobulin and mucin domain-containing molecule 4 (TIM-4) promotes the development and progression of lung cancer. However, the role of TIM-4 in mitochondria homeostasis in tumor cells remains completely unknown. In this study, we found that TIM-4 promoted growth and proliferation of lung cancer cells by the oxidative phosphorylation (OXPHOS) pathway. Consistently, inhibition of OXPHOS reversed TIM-4-induced proliferation of lung cancer cells. Notably, TIM-4 promoted mitochondrial fusion via enhancing L-OPA1 protein expression. Mechanistically, TIM-4 regulated protein of L-OPA1 through the PI3K/AKT pathway, and TIM-4 interacted with ANXA2 to promote the activation of PI3K/AKT signaling. Collectively, TIM-4 promotes oxidative phosphorylation of lung cancer cells to accelerate tumor progress via ANXA2/PI3K/AKT/OPA1 axis, which sheds significant new lights on the potential role of TIM-4 in regulating tumor cell metabolism.
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Anexina A2 , Neoplasias Pulmonares , Humanos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Neoplasias Pulmonares/genética , Mitocondrias , Homeostasis , GTP FosfohidrolasasRESUMEN
LINC00599 has been reported to be upregulated in response to cigarette smoking. However, the effect and underlying mechanism of LINC00599 in chronic obstructive pulmonary disease (COPD) are still under exploration. In this study, LINC00599 was upregulated in the COPD patients and was of clinical value to distinguish COPD patients. COPD cell models were established using 16HBE cells under cigarette smoke extract (CSE) treatment. LINC00599 levels were elevated in a dose and time-dependent way in response to CSE stimulation. The effect of LINC00599 on CSE-induced 16HBE cells was explored. The results showed that LINC00599 deficiency reversed the CSE-induced inhibition on cell viability and proliferation, and rescued the CSE-induced enhancement on cell 16HBE cell apoptosis and inflammation response. Moreover, LINC00599 bound with miR-212-5p to upregulate the BASP1 (brain abundant membrane attached signal protein 1) expression. MiR-212-5p was expressed at a low level in the tissue samples of COPD patients, and its levels were upregulated in LINC00599 silenced cells. BASP1 was targeted by miR-212-5p and its upregulation was identified in the tissue samples of COPD patients and cell models. BASP1 levels were downregulated after miR-212-5p overexpression or LINC00599 silencing. Moreover, the rescue assays demonstrated that BASP1 overexpression reversed the effect of silenced LINC00599 on 16HBE cells after CSE treatment, which indicated that LINC00599 promoted the COPD development by regulating BASP1 expression. In conclusion, LINC00599 facilitated CSE-induced cell apoptosis and inflammation response, while inhibiting the cell viability and proliferation in COPD progression via modulating miR-212-5p/BASP1 axis.
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MicroARNs , Enfermedad Pulmonar Obstructiva Crónica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Inflamación/metabolismo , Apoptosis , Células Epiteliales/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas Represoras/metabolismoRESUMEN
Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common systemic vasculitis in children, characterized by diverse clinical manifestations with a wide spectrum ranging from isolated cutaneous vasculitis to systemic involvement. The incidence of IgAV is geographically and ethnically variable, with a prevalence in autumn and winter, suggesting a driving role that genetic and environmental factors play in the disease. Although IgAV has a certain degree of natural remission, it varies widely among individuals. Some patients can suffer from severe renal involvement and even progress to end-stage renal disease. Its pathogenesis is complex and has not been fully elucidated. The formation of galactose-deficient IgA1 (Gd-IgA1) and related immune complexes plays a vital role in promoting the occurrence and development of IgAV nephritis. In addition, neutrophil activation is stimulated through the binding of IgA to the Fc alpha receptor I expressed on its surface, resulting in systemic vascular inflammation and tissue damage. Starting from the epidemiological characteristics, this article will review the role of immunological factors such as Gd-IgA1, autoantibodies, circulating immune complexes, complement system, cellular immunization, and the contributions of environmental and genetic factors in the pathogenesis of IgAV, and conclude with the major biomarkers for IgAV.
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Vasculitis por IgA , Niño , Humanos , Vasculitis por IgA/epidemiología , Complejo Antígeno-Anticuerpo , Galactosa , Inmunoglobulina A , Biomarcadores , Factores Inmunológicos , AutoanticuerposRESUMEN
The tumour suppressive role of miRNA320a is observed in many cancer types like in colon, lung, breast, and osteosarcoma but it is inversely reported in prostate cancer and in MPM cell lines. miRNA320a targets programmed death ligand 1 (PDL1) negatively in many cancer types and recently in Malignant pleural mesothelioma. In this background it is important to understand the regulatory mechanism of miRNA320a in determining PDL1 expression in different pathological stages of lung cancer. Histology was used to grade the initial and advanced stage of lung cancer following carcinogenic injection. Immunohistochemistry and Western blotting technique were used to analyse PDL1 protein expression. In-situ hybridization was used to determine miRNA320a signals. Initially, using the chemical carcinogen Diethylnitrosamine (25 µg/g), we successfully initiate initial and advanced stage of lung cancer following 6 months and 9 months of carcinogenic injection. The formation of initial and advanced stage of lung cancer is confirmed through histopathological changes which show neoplastic appearance in initial lung cancer and appearance of more mitotic cells along with tissue hardness in the advanced lung cancer stages. In miRNA320a blocked tissue the cancer condition becomes worse with decreased tissue elasticity along with more proliferative cells. Immunohistochemistry and Western blotting studies show that PDL1 is overexpressed in the advanced stages rather than in initial lung cancer because the expression of miRNA320a is overexpressed in initial stages but restricted in advanced stages of lung cancer. miRNA32a blocking studies confirm that miRNA320a expression act as a tumour suppressor that directly controls PDL1 expression that lack of miRNA320a enhances PDL1 expression as well as it triggers lung cancer advances. In summary, miRNA320a possess tumour suppressor function that limits PDL1 expression in initial lung cancer but its control over PDL1 suppression is lost once miRNA320a is downregulated in advanced stage of lung cancer.
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Antígeno B7-H1 , Neoplasias Pulmonares , MicroARNs , Animales , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinógenos , Dietilnitrosamina/toxicidad , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , MicroARNs/genética , MicroARNs/metabolismo , PronósticoRESUMEN
With the hot development of football, sports injuries caused by football have also received special attention. In football games, although there are medical staff on and off the field always on call to protect the safety of players, because of the complexity of diagnosis work, medical staff can easily lead to diagnostic errors due to factors such as fatigue, which seriously affects the condition of athletes. Image processing is a technology that uses computer to process images, which can greatly overcome the uncertain factors brought by manual diagnosis. Based on this, this paper uses image processing technology and pattern recognition as technical means to explore the specific application of image processing in football injury diagnosis. This paper firstly takes football clubs as the main research object and analyzes and explores the specific utility of image segmentation and feature recognition in sports injury image processing. Then, starting from the relevant image features, the paper analyzes and compares the sensitivity of support vector machine pattern recognition and neural network pattern recognition in football injury diagnosis. This article comprehensively summarizes the application of image processing technology in the diagnosis of football injuries and puts forward constructive suggestions for its subsequent development. Experiments show that the effect of pattern recognition is often different for different injury parts of football. Among them, the sensitivity of pattern recognition based on image processing can reach 68.9%, and the detection rate of football injuries can also be maintained at about 81.2%. This fully shows that image processing technology can play an active role in the actual football injury diagnosis, and provide very valuable information for clinical diagnosis.
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The antibiotic options available for Mycobacterium abscessus (M. abscessus) infection are limited and no definitive therapeutic strategies have been formulated. The recent discovery that rifabutin is active against M. abscessus has raised interest in using rifabutin to treat this intractable disease. In this study, we evaluated the in vitro activity of rifabutin against 194 M. abscessus clinical isolates collected during 2012 January to 2017 December. As expected, rifabutin demonstrated considerably lower MICs against M. abscessus, with an MIC50 of 2 µg/mL and MIC90 of 4 µg/mL, respectively. Notably, the anti-M.abscessus activity was even stronger among clarithromycin-insusceptible strains. In addition, M. abscessus isolates with a rough morphotype were more sensitive to rifabutin compared with those forming smooth colonies when considered as a whole or in separate subspecies. Results from synergistic experiments revealed that the in vitro activity of rifabutin was significantly enhanced by the addition of amikacin, suggesting a promising strategy for M. abscessus infection combination treatment. Finally, five and three mutation patterns in rpoB and arr, respectively, were identified among the 194 strains through whole genome sequencing. However, none of them conferred rifabutin resistance. Our study is among the first to report the susceptibility of M. abscessus to rifabutin in vitro with a large amount of clinical isolates, suggesting that rifabutin is active, both alone and in combination, against M. abscessus and is worth considering as part of a combination treatment regimen for M. abscessus infections.
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Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Antibacterianos/farmacología , Claritromicina/farmacología , Claritromicina/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Rifabutina/farmacología , Rifabutina/uso terapéuticoRESUMEN
T-cell immunoglobulin domain and mucin domain 4 (TIM-4) is a transmembrane protein that promotes epithelial-mesenchymal transition (EMT), migration and invasion of non-small cell lung cancer (NSCLC) cells. Most transmembrane proteins are modified by N-glycosylation and the importance of protein N-glycosylation in cancer cell metastasis has been well appreciated. However, whether TIM-4 is modified by N-glycosylation and the role of TIM-4 N-glycosylation in NSCLC remains largely unknown. In the current study, we reported that TIM-4 was extensively N-glycosylated at Asn291. After the removal of N-glycosylation, the stability of TIM-4 protein was decreased and TIM-4 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated ERAD. Thus, the expression of TIM-4 on the cell surface was decreased, which suppressed TIM-4-mediated metastasis in NSCLC. In summary, the present study identifies TIM-4 N-glycosylation and its role in NSCLS migration, which would provide a valuable biomarker for developing drugs targeting N-glycosylation at Asn291 on TIM-4.
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We know little about the antigen bias in SARS-CoV-2 humoral response and the epitopes of spike recognized by the immune system in asymptomatic (AS) patients and symptomatic (S) patients. Here, we used a microarray to evaluate the humoral immune response in the sera collected from 33 COVID-19-recovered patients up to 1 year. We found that the levels of IgG and IgM induced by the 23 proteins differed significantly in the same patients, and were able to distinguish AS and S patients. The N- and S-specific antibodies were detected even at 12 months after onset. Five epitopes were identified to be associated with the clinical adverse events, and three peptides located in RBD. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses between AS and S recovered patients and provide insights to promote precise development of SARS-CoV-2 vaccines.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Vacunas contra la COVID-19 , Humanos , Inmunidad Humoral , Glicoproteína de la Espiga del CoronavirusRESUMEN
Biofilm formation is an important factor for Mycobacterium abscessus to resist harsh environment and produce drug resistance. The anti-biofilm activity of a newly designed antibacterial peptide, RP557, was investigated. The effect of RP557 alone or in combination with several clinically effective antibiotics, including clarithromycin, amikacin, cefoxitin and imipenem, on M. abscessus growth in biofilms was determined. Microstructural changes in biofilms after RP557 treatment were observed by scanning electron microscope. The effect of RP557 on the viability of bacteria was determined by Syto9/PI staining and fluorescence microscopy. Finally, the potential mechanism of RP557 action on biofilm development was explored by transcriptome analysis. M. abscessus growing in biofilms showed increased resistance to antimicrobial drugs. RP557 alone exhibited only moderate anti-M. abscessus activity in vitro, but significantly increased the antibiotic sensitivity of M. abscessus in biofilms. The inhibitory effect of RP557 on biofilm formation was visualized by the scanning electron microscope; fluorescence staining demonstrated increased bacterial death in response to RP557 treatment. Furthermore, comparative analysis of transcriptomic data suggested RP557 may inhibit biofilm formation by down-regulating nitrogen and fatty acid metabolism, as well as peptidoglycan biosynthesis. As such, RP557 is a potential candidate to include in novel strategies to treat M. abscessus infections.
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Mycobacterium abscessus , Antibacterianos/farmacología , Biopelículas , PéptidosRESUMEN
Metal halide perovskite (MHP) nanocrystals (NCs) have shown promising application in photocatalytic CO2 reduction, but their activities are still largely restrained by severe charge recombination and narrow solar spectrum response. Assembly of heterojunctions can be beneficial to the charge separation in MHPs while the assembly process usually brings native interfacial defects, impeding efficient charge separation between two materials. Herein, an in-situ generation strategy was developed to prepare CsPbBr3 /WO3 heterojunction, using WO3 nanosheets (NSs) as growing substrate for the growth of CsPbBr3 NCs. The developed CsPbBr3 /WO3 heterojunction exhibited a high-quality interface, greatly facilitating charge transfer between two semiconductors. The hybrid photocatalyst displayed an excellent activity toward CO2 reduction, which was about 7-fold higher than pristine CsPbBr3 NCs and 3.5-fold higher than their assembled counterparts. The experimental results and theoretical simulations revealed that a Z-scheme mechanism with a favorable internal electric field was responsible for the good performance of CsPbBr3 /WO3 heterojunction. By using O-defective WO3 NSs as a near-infrared (NIR) light absorber, the CsPbBr3 /WO3 heterojunction could harvest NIR light and showed an impressive activity toward CO2 reduction. This work demonstrates a new strategy to design MHP-based heterojunctions by synergistically considering the interface quality, charge transfer mode, interfacial electric field, and light response range between two semiconductors.
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The superhydrophobic surface can be prepared by two methods; one is by reducing the surface energy, and the other is by constructing a micro-nano rough structure. To achieve high superhydrophobic performance in terms of durability, the firm combination of hydrophobic coating and substrate is particularly important. Here, we use polydimethylsiloxane (PDMS) as a low surface energy monomer, water-borne polyurethane (WPU) as a dispersing aid, and use high-power ultrasound to disperse PDMS in water to make emulsion. The polyester matrix is etched by atmospheric plasma, dipped in PDMS emulsion, dried, and finally baked to induce PDMS on the surface of polyester fiber to cross-link into film. A series of tests on the self-cleaning polyester fabric prepared by this method show that when the concentration of PDMS is 8 g/L and the mass ratio of PDMS to WPU is 20:1, the water contact angle (WCA) reaches the maximum value of 148.2°, which decreases to 141.5° after 200 times of washing and 138.6° after 5000 times of rubbing. Before and after PDMS coating, the tensile strength of polyester fabric increases from 489.4 N to 536.4 N, and the water vapor transmission decreases from 13,535.7 g/(m2·d) to 12,224.3 g/(m2·d). This research is helpful to the large-scale production of self-cleaning polyester fabric. In the future, on the basis of this research, we will add functional powder to endow self-cleaning polyester fabric with higher hydrophobicity and other properties.