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Two-dimensional (2D) semiconductors have attracted intense interest for their unique photophysical properties, including large exciton binding energies and strong gate tunability, which arise from their reduced dimensionality1-5. Despite considerable efforts, a disconnect persists between the fundamental photophysics in pristine 2D semiconductors and the practical device performances, which are often plagued by many extrinsic factors, including chemical disorder at the semiconductor-contact interface. Here, by using van der Waals contacts with minimal interfacial disorder, we suppress contact-induced Shockley-Read-Hall recombination and realize nearly intrinsic photophysics-dictated device performance in 2D semiconductor diodes. Using an electrostatic field in a split-gate geometry to independently modulate electron and hole doping in tungsten diselenide diodes, we discover an unusual peak in the short-circuit photocurrent at low charge densities. Time-resolved photoluminescence reveals a substantial decrease of the exciton lifetime from around 800 picoseconds in the charge-neutral regime to around 50 picoseconds at high doping densities owing to increased exciton-charge Auger recombination. Taken together, we show that an exciton-diffusion-limited model well explains the charge-density-dependent short-circuit photocurrent, a result further confirmed by scanning photocurrent microscopy. We thus demonstrate the fundamental role of exciton diffusion and two-body exciton-charge Auger recombination in 2D devices and highlight that the intrinsic photophysics of 2D semiconductors can be used to create more efficient optoelectronic devices.
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Electrocatalytic hydrogen evolution reaction (HER) is critical for green hydrogen generation and exhibits distinct pH-dependent kinetics that have been elusive to understand. A molecular-level understanding of the electrochemical interfaces is essential for developing more efficient electrochemical processes. Here we exploit an exclusively surface-specific electrical transport spectroscopy (ETS) approach to probe the Pt-surface water protonation status and experimentally determine the surface hydronium pKa [Formula: see text] 4.3. Quantum mechanics (QM) and reactive dynamics using a reactive force field (ReaxFF) molecular dynamics (RMD) calculations confirm the enrichment of hydroniums (H3O[Formula: see text]) near Pt surface and predict a surface hydronium pKa of 2.5 to 4.4, corroborating the experimental results. Importantly, the observed Pt-surface hydronium pKa correlates well with the pH-dependent HER kinetics, with the protonated surface state at lower pH favoring fast Tafel kinetics with a Tafel slope of 30 mV per decade and the deprotonated surface state at higher pH following Volmer-step limited kinetics with a much higher Tafel slope of 120 mV per decade, offering a robust and precise interpretation of the pH-dependent HER kinetics. These insights may help design improved electrocatalysts for renewable energy conversion.
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Electroquímica , Hidrógeno , Platino (Metal) , Concentración de Iones de Hidrógeno , Cinética , Platino (Metal)/química , Energía Renovable , AguaRESUMEN
OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.
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Excessive autophagy may lead to degradation and damage of alveolar epithelial cells after lung transplantation, eventually leading to alveolar epithelial cell loss, affecting the structural integrity and function of alveoli. Glutamine (Gln), a nutritional supplement, regulates autophagy through multiple signaling pathways. In this study, we explored the protective role of Gln on alveolar epithelial cells by inhibiting autophagy. In vivo, a rat orthotopic lung transplant model was carried out to evaluate the therapeutic effect of glutamine. Ischemia/reperfusion (I/R) induced alveolar collapse, edema, epithelial cell apoptosis, and inflammation, which led to a reduction of alveolar physiological function, such as an increase in peak airway pressure, and a decrease in lung compliance and oxygenation index. In comparison, Gln preserved alveolar structure and function by reducing alveolar apoptosis, inflammation, and edema. In vitro, a hypoxia/reoxygenation (H/R) cell model was performed to simulate IR injury on mouse lung epithelial (MLE) cells and human lung bronchus epithelial (Beas-2B) cells. H/R impaired the proliferation of epithelial cells and triggered cell apoptosis. In contrast, Gln normalized cell proliferation and suppressed I/R-induced cell apoptosis. The activation of mTOR and the downregulation of autophagy-related proteins (LC3, Atg5, Beclin1) were observed in Gln-treated lung tissues and alveolar epithelial cells. Both in vivo and in vitro, rapamycin, a classical mTOR inhibitor, reversed the beneficial effects of Gln on alveolar structure and function. Taken together, Glnpreserved alveolar structure and function after lung transplantation by inhibiting autophagy.
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Autofagia , Glutamina , Trasplante de Pulmón , Alveolos Pulmonares , Ratas Sprague-Dawley , Daño por Reperfusión , Autofagia/efectos de los fármacos , Animales , Glutamina/metabolismo , Glutamina/farmacología , Masculino , Humanos , Ratones , Ratas , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Apoptosis/efectos de los fármacos , Línea Celular , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/efectos de los fármacos , Células Epiteliales Alveolares/patologíaRESUMEN
Guided by the Global Natural Products Social (GNPS) molecular networking strategy, five undescribed eremophilane-type sesquiterpenoid derivatives (1-5) were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of plant Hypericum beanii collected in Shennongjia Forestry District, Hubei Province. Dipeniroqueforins A-B (1-2), representing a lactam-type sesquiterpenoid skeleton with a highly symmetrical and homodimeric 5/6/6-6/6/5 hexacyclic system, are reported within the eremophilane-type family for the first time. Peniroqueforin D (5) represents the first example of a 1,2-seco eremophilane-type sesquiterpenoid derivative featuring an undescribed 7/6-fused ring system. The structures of these compounds were elucidated by various spectroscopic analyses, DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, these isolates were evaluated for cytotoxicity, and the result uncovered that compound 1 displayed broad-spectrum activity. Further mechanistic study revealed that compound 1 could significantly upregulate the mRNA expression of genes related to the oxidative induction, leading to the abnormal ROS levels in tumor cells and ultimately causing tumor cell apoptosis.
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Antineoplásicos , Penicillium , Sesquiterpenos , Sesquiterpenos Policíclicos , Estructura Molecular , Sesquiterpenos/química , Penicillium/química , Antineoplásicos/químicaRESUMEN
Bisphenols, parabens, and triclosan (TCS) are common endocrine disrupters used in various consumer products. These chemicals have been shown to cross the placental barrier and affect intrauterine development of fetuses. In this study, we quantified serum levels of six bisphenols, five parabens, and TCS in 483 pregnant women from southern China. Quantile-based g-computation showed that combined exposure to bisphenols, parabens, and TCS was significantly (p < 0.05) and negatively associated with birth weight (ß = -39.9, 95% CI: -73.8, -6.1), birth length (ß = -0.19, 95% CI: -0.34, -0.04), head circumference (ß = -0.13, 95% CI: -0.24, -0.02), and thoracic circumference (ß = -0.16, 95% CI: -0.29, -0.04). An inverse correlation was also identified between mixture exposure and gestational age (ß = -0.12, 95% CI: -0.24, -0.01). Bisphenol A (BPA), bisphenol Z (BPZ), bisphenol AP (BPAP), propylparaben (PrP), and TCS served as the dominant contributors to the overall effect. In subgroup analyses, male newborns were more susceptible to mixture exposure than females, whereas the exposure-outcome link was prominent among pregnant women in the first and second trimesters. More evidence is warranted to elucidate the impacts of exposure to mixtures on birth outcomes, as well as the underlying mechanisms.
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Peso al Nacer , Edad Gestacional , Parabenos , Fenoles , Triclosán , Humanos , Femenino , Embarazo , Peso al Nacer/efectos de los fármacos , Adulto , Masculino , Recién Nacido , Exposición Materna , Disruptores Endocrinos , Compuestos de Bencidrilo , China , Trimestres del EmbarazoRESUMEN
The N-oxide strategy plays a crucial role in regulating the performance and safety of energetic materials. This study mainly addresses the question of how the N-oxide group affects the properties of azobistriazole and its derivatives. Our findings indicate that the N-oxide group can increase the density of the system, and its effect on the enthalpy of formation depends on the specific situation. The N-oxide groups can effectively improve the density and energetic properties. Some of the energetic derivatives containing N-oxide groups have a density as high as 2.097 g cm-3 (D3-NO(2)) and a detonation velocity as high as 10 275 m s-1 (C6-NO(2)). The effect of N-oxide groups on the enthalpy of formation depends on the specific circumstances. The effect of N-oxide groups on the stability of azobistriazole energetic derivatives is relatively complex. Among them, the N-oxide group on the triazole ring has an opposite effect on the bond dissociation enthalpy of functional groups. When the N-oxide group is on the 1,2,3-triazole ring, it can improve C-R (R is equal to C(NO2)3, NF2, NHNO2, NO2, and ONO2 respectively) bond dissociation enthalpy, and when it is on the 1,2,4-triazole ring, it will reduce the C-R bond dissociation enthalpy. When the N-oxide group is located on the azo bond, the bond dissociation enthalpy of the azo bond will be significantly reduced. This article systematically explores the effect of N-oxide groups on the properties of azobistriazole energetic derivatives, which will help people better utilize N-oxide groups to design and synthesize new energetic materials.
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BACKGROUND: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. METHODS: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. RESULTS: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group. CONCLUSIONS: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status.
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Gastrectomía , Laparoscopía , Desnutrición , Procedimientos Quirúrgicos Robotizados , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones , Gastrectomía/métodos , Masculino , Femenino , Laparoscopía/métodos , Desnutrición/etiología , Procedimientos Quirúrgicos Robotizados/métodos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Tiempo de Internación/estadística & datos numéricos , Tempo Operativo , Puntaje de PropensiónRESUMEN
INTRODUCTION: Cryobiopsy (CB) using a 1.1-mm cryoprobe under fluoroscopic guidance is feasible and safe for diagnosis of ground glass opacity (GGO) lesions. However, the efficacy of CB combined with cone-beam CT (CBCT) for GGO-predominant pulmonary nodules remains elusive. METHODS: We retrospectively studied patients who underwent CB combined with conventional biopsy under CBCT guidance for GGO-predominant pulmonary nodules with a consolidation-to-tumour ratio <50.0%. RESULTS: A total of 32 patients with GGO-predominant pulmonary nodules were enrolled: 17 pure GGOs and 15 mixed GGOs. The mean lesion diameter was 15.81 ± 5.52 mm and the overall diagnostic yield was 71.9%. Seven lesions were diagnosed by CB alone, which increased the diagnostic outcomes by 21.9%. Diagnostic yields for CB, forceps biopsy (FB), brushing, and guide sheath flushing were 65.6%, 46.9%, 15.6%, and 14.3%, respectively. Univariate analysis revealed that positive computed tomography (CT) bronchus sign (p = 0.035), positive CBCT sign (p < 0.01), and CB-first biopsy sequence (p = 0.036) were significant predictive factors for higher diagnostic yield. Specimens obtained by CB had larger mean sample size (p < 0.01), lower blood cell area (p < 0.01), and fewer crush artefacts (p < 0.01) than specimens from FB. No severe bleeding or other complications occurred. CONCLUSION: CB using a 1.1-mm cryoprobe under CBCT guidance increased diagnostic yield for GGO-predominant pulmonary nodules based on conventional biopsy. Further, it provided larger and nearly intact samples compared with forceps.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Biopsia/métodos , Tomografía Computarizada de Haz Cónico , Nódulos Pulmonares Múltiples/diagnóstico por imagenRESUMEN
In this work, complex Chinese micropatterns are experimentally inscribed in AgInSbTe thin films through laser writing technique. The overlapping inscription strategy is introduced to reduce the size of complex Chinese micropatterns, and the erosion algorithm is used to eliminate sticking effects among fine strokes in complex Chinese micropatterns. The results show that the size of complex Chinese micropatterns can be reduced to around 15.41µm×15.41µm. The width of the finest stroke is only 0.45 µm. This method can achieve a fidelity of 95%. This work helps with the long-term preservation of massive Chinese character archives.
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PURPOSE OF REVIEW: Tension-type headaches (TTH) significantly diminish patients' quality of life and increase absenteeism, thereby imposing a substantial economic burden. Animal models are essential tools for studying disease mechanisms and drug development. However, until now, little focus has been placed on summarizing the animal models of TTH and associated mechanistic studies. This narrative review discusses the current animal models of TTH and related mechanistic studies to provide insights into the pathophysiological mechanisms of and treatments for TTH. RECENT FINDINGS: The primary method for constructing an animal model of TTH involves injecting a solution of pain relievers, such as adenosine triphosphate, nerve growth factor, or a high concentration of salt solution, into the neck to initiate harmful cervical muscle responses. This model enables the examination of the interaction between peripheral muscles and central sensitization, which is crucial for understanding the pathophysiology of TTH. Mechanistic studies based on this model have investigated the effect of the P2X receptor antagonist, P2X7 receptor blockade, the P2Y1 receptor agonist 2-MESADP, P2Y1 receptor antagonist MRS2179, nitric oxide synthase inhibitors, and acetylsalicylic acid. Despite notable advancements, the current model of TTH has limitations, including surgical complexity and the inability to replicate chronic tension-type headache (CTTH). To gain a more comprehensive understanding and develop more effective treatment methods, future studies should focus on simplifying surgical procedures, examining other predisposing factors, and establishing a model for chronic TTH. This will offer a deeper insight into the pathophysiological mechanism of TTH and pave the way for improved treatment approaches.
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Modelos Animales de Enfermedad , Cefalea de Tipo Tensional , Cefalea de Tipo Tensional/fisiopatología , Cefalea de Tipo Tensional/tratamiento farmacológico , Cefalea de Tipo Tensional/terapia , Animales , HumanosRESUMEN
Daunorubicin (DNR-) induced cardiotoxicity seriously restricts its clinical application. Transient receptor potential cation channel subfamily C member 6 (TRPC6) is involved in multiple cardiovascular physiological and pathophysiological processes. However, the role of TRPC6 anthracycline-induced cardiotoxicity (AIC) remains unclear. Mitochondrial fragmentation greatly promotes AIC. TRPC6-mediated ERK1/2 activation has been shown to favor mitochondrial fission in dentate granule cells. The aim of the present study was to elucidate the effects of TRPC6 on daunorubicin- induced cardiotoxicity and identify the mechanisms associated with mitochondrial dynamics. The sparkling results showed that TRPC6 was upregulated in models in vitro and in vivo. TRPC6 knockdown protected cardiomyocytes from DNR-induced cell apoptosis and death. DNR largely facilitated mitochondrial fission, boosted mitochondrial membrane potential collapse and damaged debilitated mitochondrial respiratory function in H9c2 cellsï¼these effects were accompanied by TRPC6 upregulation. siTRPC6 effectively inhibited these mitochondrial adverse aspects showing a positive unexposed effect on mitochondrial morphology and function. Concomitantly, ERK1/2-DRP1 which is related to mitochondrial fission was significantly activated with amplified phosphorylated forms in DNR-treated H9c2 cells. siTRPC6 effectively suppressed ERK1/2-DPR1 over activation, hinting at a potential correlation between TRPC6 and ERK1/2-DRP1 by which mitochondrial dynamics are possibly modulated in AIC. TRPC6 knockdown also raised the Bcl-2/Bax ratio, which may help to block mitochondrial fragmentation-related functional impairment and apoptotic signaling. These findings suggested an essential role of TRPC6 in AIC by intensifying mitochondrial fission and cell death via ERK1/2-DPR1, which could be a potential therapeutic target for AIC.
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Daunorrubicina , Miocitos Cardíacos , Canal Catiónico TRPC6 , Animales , Ratas , Apoptosis , Cardiotoxicidad/metabolismo , Muerte Celular , Daunorrubicina/toxicidad , Dinaminas/metabolismo , Sistema de Señalización de MAP Quinasas , Dinámicas Mitocondriales , Miocitos Cardíacos/metabolismo , Canales Catiónicos TRPC/genética , Canales Catiónicos TRPC/metabolismo , Canal Catiónico TRPC6/metabolismoRESUMEN
Oral cancer, primarily oral squamous cell carcinomas (OSCC), is a major health concern worldwide. The current gold standard for the diagnosis of OSCC is biopsy and histopathological analysis, which is invasive and can place a huge financial burden on the healthcare system. Optical coherence tomography-based angiography (OCTA) is a non-invasive imaging technique that shows promise as an imaging modality to aid the diagnosis of OSCC. This Letter outlines the development of a handheld intraoral OCT probe applied to a swept-source OCT system with an angiography function for oral applications. The probe has a thin body with a diameter of 17.8 mm and a two-lens system with a working distance that is adjustable from 20.92 mm to 24.08 mm, a field of view 9 mm in diameter, an imaging depth of â¼1.7 mm, and resolutions of 39.38â µm (laterally) and 33.37â µm (axially). This probe was used to scan 14 oral sites to evaluate its ability to scan various sites in the oral cavity. This system has the potential to reduce invasive procedures and aid early OSCC diagnosis.
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Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Tomografía de Coherencia Óptica , Angiografía , Neoplasias de la Boca/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagenRESUMEN
We report an all-Si microring (MRR) avalanche photodiode (APD) with an ultrahigh responsivity (R) of 65 A/W, dark current of 6.5 µA, and record gain-bandwidth product (GBP) of 798â GHz at -7.36â V. The mechanisms for the high responsivity have been modelled and investigated. Furthermore, open eye diagrams up to 20 Gb/s are supported at 1310â nm at -7.36â V. The device is the first, to the best of our knowledge, low cost all-Si APD that has potential to compete with current commercial Ge- and III-V-based photodetectors (PDs). This shows the potential to make the all-Si APD a standard "black-box" component in Si photonics CMOS foundry platform component libraries.
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BACKGROUND: A large proportion of the patients with cancer do not respond to immunotherapies. Recent studies suggested an important role for tumor-infiltrating cytotoxic T lymphocytes (CTL) in enhancing response to immunotherapy. Here, we aim to identify gene that induce proliferative and cytotoxic states of CD8+ T cells, and to investigate its effect on CAR-T cells against colorectal cancer. METHODS: Correlation between the expression of IFI35 with the activation and cytotoxicity of CD8+ T cells was assessed with TCGA and proteomic databases. Then we constructed murine colon cancer cells over-expressing IFI35 and tested their effect on anti-tumor immunity in both immunodeficient and immunocompetent mouse models. Flow cytometry and immunohistochemistry were performed to assess the immune microenvironment. Western blot analysis was used to identify the potential down-stream signaling pathway regulated by IFI35. We further investigated the efficacy of the rhIFI35 protein in combination with immunotherapeutic treatment. RESULTS: The transcriptional and proteomic analysis of the activation and cytotoxicity of CD8+ T cells in human cancer samples demonstrated that IFI35 expression is correlated with increased CD8+ T cell infiltration and predicted a better outcome in colorectal cancer. The number and cytotoxicity of CD8+ T cells were significantly increased in IFI35-overexpressing tumors. Mechanistically, we identified that the IFNγ-STAT1-IRF7 axis stimulated IFI35 expression, and that IFI35-mediated regulation of CD8+ T cell proliferation and cytotoxicity was dependent on PI3K/AKT/mTOR signaling pathway in vitro. Furthermore, IFI35 protein enhanced the efficacy of CAR-T cells against colorectal cancer cells. CONCLUSION: Our findings identify IFI35 as a new biomarker that can enhance the proliferation and function of CD8+ T cells, as well as increase the efficacy of CAR-T cells against colorectal cancer cells.
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Antineoplásicos , Neoplasias del Colon , Humanos , Animales , Ratones , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt/genética , Linfocitos T CD8-positivos , Proteómica , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Microambiente TumoralRESUMEN
Autophagy is a conservative and important process that exists in all eukaryotic cells in nature. Cyprinid herpesvirus 3 (CyHV-3), also known as KHV (Koi Herpesvirus), is a pathogen that mainly infecting common carp and koi. In the present study, we identified the CcLC3B gene, with a length of 379 bp and displaying a close evolutionary relationship with other sixteen different species, the tissue distribution and expression pattern of CcLC3 were also identified. We found that CyHV-3 infection could promote autophagy in CCB cells at the early stage but inhibit autophagy at the late stage by using confocal fluorescence microscopy, transmission electron microscopy and western blotting. And we measured the protein levels associated with the Akt/mTOR signalling pathway, intracellular replication of CyHV-3 at the mRNA and protein levels as well as viral titters. Collectively, the results taken together suggested that CyHV-3 infection could promote autophagy in CCB cells at the early stage but inhibit autophagy at the late stage via mTOR and that promoting autophagy could facilitate CyHV-3 intracellular replication and extracellular viral yields in CCB cells. These findings revealed the relationship between CyHV-3 and autophagy and provided a novel treatment strategy targeting the autophagy signalling pathway against CyHV-3 infection.
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Cyprinid herpesvirus type 3 (CyHV-3), also called Koi herpesvirus (KHV), which leads to mass cyprinid mortality and enormous economic losses. To establish an infection, CyHV-3 needs to counteract host antiviral responses. CD81 belongs to the evolutionary conserved tetraspanin family of proteins. Several studies have shown that different members of the tetraspanin superfamily modulates different virus infectious processes. Here we aimed at analysing the role of CD81 in CyHV-3 infection. In this study, we cloned and characterized the CD81 of Common Carp, the open reading frame of CcCD81 gene was 702 bp, which encoded 234 amino acids with four transmembrane domains (TM1 to TM4), a small extracellular loop (SEL), and a large extracellular loop (LEL). Tissue distribution analysis showed that CcCD81 was widely expressed in all the tested tissues with the highest expression in head kidney, followed by a high expression in brain. Subsequently, expression levels of CcCD81 were significantly increased in CCB cells within the first 3h after infection, meanwhile, the expression of viral gene VP136 was reduced after CcCD81 knockdown in CCB cells post CyHV-3 infection. Furthermore, CcCD81 knockdown can significantly reduce the autophagy process and increase the promoter activity of ISRE and IFN-1 in the CCB cells after viral infection, as well as other genes involved in the IFN signaling pathway, including RIG-1ãMDA5ãMAVSãTBK1 and IRF3. Taking the data together, we revealed that CcCD81 mediates autophagy and blocks RIG-1-mediated antiviral signaling and negatively regulates the promoter activity of type I interferon (IFN) promoting virus replication. These results reveal a new link between autophagy and four-transmembrane-domain protein superfamily and contribute to elucidate the mechanism of CyHV-3 infection.
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Carpas , Enfermedades de los Peces , Infecciones por Herpesviridae , Herpesviridae , Interferón Tipo I , Animales , Infecciones por Herpesviridae/veterinaria , Carpas/genética , Carpas/metabolismo , Herpesviridae/fisiología , Interferón Tipo I/genética , Antivirales , Autofagia , Transducción de Señal , Tetraspaninas , Replicación ViralRESUMEN
PURPOSE: The aim of the study was to compare and explore the agreement between the nomogram tool and ultrasound biomicroscopy (UBM) images method to calculate the ultrasound cycloplasty (UCP) probe model in Chinese glaucoma patients. METHODS: Retrospective analysis of Chinese glaucoma patients who visited Zhongshan Ophthalmic Center in Guangzhou from January to December 2019 and were eligible for UCP surgery. Visual acuity, intraocular pressure (IOP), ocular axial length (AL), and horizontal corneal diameter (white to white [WTW]) were measured. UBM images with clear ciliary body imaging and AL and WTW data were sent to trained personnel for probe model measurements. The data calculated by both methods were analyzed using unweighted and weighted κ statistics. The level of agreement refers to Landis and Koch's guideline for the strength of agreement indicated with weighted κ values. RESULTS: 1,061 eyes of 642 patients were involved, with a mean age of 61.66 ± 11.66 years. Their best-corrected visual acuity converted to logarithm of minimal-angle-of-resolution (logMAR) scores of -0.18-3.00 with a mean value of 0.69 ± 0.77. IOP was 22.0-60.0 mm Hg with a mean of 27.97 ± 5.66 mm Hg. The mean AL and WTW were 22.88 ± 1.33 (19.15-32.14) mm and 11.52 ± 0.49 (10.00-12.90) mm, respectively. The agreement between the two methods was fair (weighted κ = 0.299), matching in 62.86% of eyes (weighted κ = 0.299, κ = 0.264). The agreement in primary open angle glaucoma, acute primary angle-closure glaucoma, chronic primary angle-closure glaucoma, and secondary glaucoma patients was 60.85% (weighted κ = 0.336, κ = 0.301), 65.06% (weighted κ = 0.146, κ = 0.127), 62.26% (weighted κ = 0.204, κ = 0.184), and 57.97% (weighted κ = 0.332, κ = 0.280) of eyes, respectively. CONCLUSION: The agreement between UBM images and the nomogram tool to calculate the UCP probe model of Chinese patients is at a fair level. The nomogram tool prefers to use larger probes. Improvements to the nomogram tool, such as including data from more ethnic groups and being able to calculate separately for different types of glaucoma, are needed to improve accuracy. The inclusion of parameters or images from more directions of the eye may help measure probe models more accurately for both the nomogram tool and the UBM image measurement.
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Glaucoma de Ángulo Cerrado , Glaucoma de Ángulo Abierto , Humanos , Persona de Mediana Edad , Anciano , Microscopía Acústica/métodos , Estudios Retrospectivos , Glaucoma de Ángulo Abierto/diagnóstico por imagen , Glaucoma de Ángulo Abierto/cirugía , Nomogramas , Presión Intraocular , ChinaRESUMEN
Recent advances in electronics miniaturization have led to the development of low-power, low-cost, point-of-care ultrasound scanners. Low-cost systems employing simple bi-level pulse generation devices need only utilize binary phase modulated coded excitations to significantly improve sensitivity; however the performance of complementary codes in the presence of nonlinear harmonic distortion has not been thoroughly investigated. Through simulation, it was found that nonlinear propagation media with little attenuative properties can significantly deteriorate the Peak Sidelobe Level (PSL) performance of complementary Golay coded pulse compression, resulting in PSL levels of -62 dB using nonlinear acoustics theory contrasted with -198 dB in the linear case. Simulations of 96 complementary pairs revealed that some pairs are more robust to sidelobe degradation from nonlinear harmonic distortion than others, up to a maximum PSL difference of 17 dB between the best and worst performing codes. It is recommended that users consider the effects of nonlinear harmonic distortion when implementing binary phase modulated complementary Golay coded excitations.
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Acústica , Ultrasonografía/métodos , Simulación por ComputadorRESUMEN
OBJECTIVES: This study aimed to assess the activity, distribution, and colocalization of cathepsin K (catK) and matrix metalloproteases (MMPs) in both intact and eroded dentin in vitro. MATERIALS AND METHODS: Eroded dentin was obtained by consecutive treatment with 5% citric acid (pH = 2.3) for 7 days, while intact dentin remained untreated. Pulverized dentin powder (1.0 g) was extracted from both intact and eroded dentin using 5 mL of 50 mM Tris-HCl buffer (0.2 g/1 mL, pH = 7.4) for 60 h to measure the activity of catK and MMPs spectrofluorometrically. In addition, three 200-µm-thick dentin slices were prepared from intact and eroded dentin for double-labeling immunofluorescence to evaluate the distribution and colocalization of catK and MMPs (MMP-2 and MMP-9). The distribution and colocalization of enzymes were analyzed using inverted confocal laser scanning microscopy (CLSM), with colocalization rates quantified using Leica Application Suite Advanced Fluorescent (LAS AF) software. One-way analysis of variance (ANOVA) was used to analyze the fluorescence data related to enzyme activity (α = 0.05). RESULTS: The activity of catK and MMPs was significantly increased in eroded dentin compared with intact dentin. After erosive attacks, catK, MMP-2, and MMP-9 were prominently localized in the eroded regions. The colocalization rates of catK with MMP-2 and MMP-9 were 13- and 26-fold higher in eroded dentin, respectively, than in intact dentin. CONCLUSIONS: Erosive attacks amplified the activity of catK and MMPs in dentin while also altering their distribution patterns. Colocalization between catK and MMPs increased following erosive attacks. CLINICAL RELEVANCE: CatK, MMP-2, and MMP-9 likely play synergistic roles in the pathophysiology of dentin erosion.