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Organic transistors based on organic semiconductors together with quantum dots (QDs) are attracting more and more interest because both materials have excellent optoelectronic properties and solution processability. Electronics based on nontoxic QDs are highly desired considering the potential health risks but are limited by elevated surface defects, inadequate stability, and diminished luminescent efficiency. Herein, organic synaptic transistors based on environmentally friendly ZnSe/ZnS core/shell QDs with passivating surface defects are developed, exhibiting optically programmable and electrically erasable characteristics. The synaptic transistors feature linear multibit storage capability and wavelength-selective memory function with a retention time above 6000 s. Various neuromorphic applications, including memory enhancement, optical communication, and memory consolidation behaviors, are simulated. Utilizing an established neuromorphic model, accuracies of 92% and 91% are achieved in pattern recognition and complicated electrocardiogram signal processing, respectively. This research highlights the potential of environmentally friendly QDs in neuromorphic applications and health monitoring.
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It has been reported that it was selective to produce ammonia on metallic cobalt in the electrocatalytic nitric oxide reduction reaction (eNORR), where hexagonal close-packed (hcp) cobalt outperforms face-centered cubic (fcc) cobalt. However, hydroxylamine is more selectively produced on a cobalt single-atom catalyst (Co-SAC). Herein, we uncover the structural sensitivity over hcp-Co, fcc-Co, and Co-SAC in eNORR by employing a recently developed constant potential simulation method and microkinetic modeling. It was found that the superior activity for ammonia production on hcp-Co can be attributed to its facile electron and proton transfer and a stronger lateral suppression effect from NO* over fcc-Co. The exceptional hydroxylamine selectivity on Co-SAC is due to the modified electronic structure, namely, a positively charged active center. It was found that it is more favorable to produce NOH* over hcp-Co and fcc-Co, while HNO* is more preferable on Co-SAC, which are firmly correlated with the vertical and strong NO adsorption on the former and the moderate adsorption on the latter. In other words, a key factor for selectivity control is the first step of NO* protonation. Therefore, the local structure and electronic structure of the catalysts can be critical in regulating the activity and selectivity in eNORR.
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AIMS: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses a significant threat to human health, necessitating urgent development of new antimicrobial agents. Silver nanoparticles (AgNPs), which are among the most widely used engineered nanomaterials, have been extensively studied. However, the impact of AgNPs on CRKP and the potential for drug resistance development remain inadequately explored. METHODS AND RESULTS: In this study, broth dilution method was used to determine the minimum inhibitory concentration (MIC) was determined using the broth dilution method. Results indicated MIC values of 93.1 ± 193.3 µg ml-1 for AgNPs, 2.3 ± 5.1 µg ml-1 for AgNO3, and 25.1 ± 48.3 µg ml-1 for imipenem (IMI). The combined inhibitory effect of AgNPs and IMI on CRKP was assessed using the checkerboard method. Moreover, after 6-20 generations of continuous culture, the MIC value of AgNPs increased 2-fold. Compared to IMI, resistance of Kl. pneumoniae to AgNPs developed more slowly, with a higher fold increase in MIC observed after 20 generations. Whole-genome sequencing revealed four nonsynonymous single nucleotide polymorphism mutations in CRKP after 20 generations of AgNP treatment. CONCLUSION: We have demonstrated that AgNPs significantly inhibit CRKP isolates and enhance the antibacterial activity of imipenem against Kl. pneumoniae. Although the development of AgNP resistance is gradual, continued efforts are necessary for monitoring and studying the mechanisms of AgNP resistance.
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Antibacterianos , Carbapenémicos , Imipenem , Klebsiella pneumoniae , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Plata , Imipenem/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Plata/farmacología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Humanos , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Farmacorresistencia Bacteriana/genéticaRESUMEN
Artificial reefs (ARs) are a preferred option for managers due to their distinctive hydrodynamic properties, which support a highly productive local ecosystem. However, the hydrodynamics characteristics of ARs in natural marine environments have not been conducted. Being the first to explore the spatiotemporal characteristic of flow fields around ARs along tidal cycles in marine environments, this study redefined the upwelling and downwelling of ARs, based on natural vertical velocities, and separated the upwelling into co-direction upwelling and re-direction upwelling, and the downwelling into co-direction downwelling and re-direction downwelling. This study simulated the flow field in the Wanshan ARs area of the Pearl River Estuary along the tidal cycles using the MIKE3-FM. Numerical simulations revealed that (1) co-direction upwelling and co-direction downwelling were the dominant components of the vertical flow field effects of ARs; (2) the areas sum of upwelling and downwelling were largest in the medium water column, with about 1.6 and 1.03 times as large as the bottom and surface water column, respectively, while the fluxes sum of the upwelling and downwelling were largest in bottom water column, with approximately 1.3 and 2.2 times larger than those in the middle and surface water columns; (3) the area and volume of the upwelling and downwelling gradually decreased along neap-spring tide, exhibited significantly negative correlations with current speeds; while the upwelling flux and downwelling flux gradually increased along neap-spring tide; exhibited a significantly positive correlation with current speed; (4) the effects of tide to upwelling and downwelling of AR are forced by the northward velocity of current speed, the net flux of upwelling and downwelling showed a significant positive correlation with the northward velocity of current speed (r = 0.94). These results could provide a reference for assessing the flow field effect of ARs and a guide for the configuration and management of ARs.
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Estuarios , Ríos , Ecosistema , Arrecifes de Coral , Hidrodinámica , Movimientos del AguaRESUMEN
PURPOSE: Our study was to investigate the correlation correlation between FDG uptake and PD-L1 expression of liver metastasis in patients with colon cancer, and to determine the value of FDG-PET in predicting PD-L1 expression in liver metastasis of colon cancer. METHODS: A total of 72 patients with confirmed liver metastasis of colon cancer were included in this retrospective study. The PD-L1 expression and immune cell infiltrating of tumors were determined through immunohistochemistry staining. The SUVmax of liver metastasis lesions were assessed using 18 F-FDG PET/CT. The correlation between PD-L1 expression and the clinicopathological were evaluated by the Cox proportional hazards model and the Kaplan-Meier survival analysis. RESULTS: PD-L1 expression was significantly correlated with FDG uptake (SUVmax), tumor size, differentiation, survival and cytotoxic T cells infiltration in liver metastasis of colon cancer (P < 0.05). And liver metastases with high counts of infiltrating cytotoxic T cells showed greater FDG uptake than those with low counts of infiltrating cytotoxic T cells. The SUVmax of liver metastases and the degree of differentiation of metastases were closely related to PD-L1 expression, and were independent risk factors.The combined assessment of SUVmax values and tthe degree of differentiation of metastase can help determine PD-L1 expression in liver metastasis of colon cancer. CONCLUSIONS: FDG uptake in liver metastasis of colon cancer was positively correlated with the PD-L1 expression and the number of cytotoxic T cells infiltration. The joint evaluation of two parameters, SUVmax and degree of differentiation, can predict PD-L1 expression in liver metastases.
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Antígeno B7-H1 , Neoplasias del Colon , Neoplasias Hepáticas , Neoplasias del Colon/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Humanos , Antígeno B7-H1/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Linfocitos T Citotóxicos , Masculino , Femenino , Persona de Mediana Edad , AncianoRESUMEN
Renal clear cell carcinoma (ccRCC) and the tumor microenvironment (TME) influence each other, leading to the tumor microenvironment that can guide the corresponding treatment. With the deepening of research, some treatment options have achieved good results, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, and so on. As the link between TME and malignancy is constantly discovered, more targeted studies on different components of TME are increasing, and this targeted therapy is a new method for treating ccRCC, and also a current research hotspot. This review summarizes the characteristics of the ccRCC tumor microenvironment, the outcomes of different treatments, and some potential targets.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Microambiente Tumoral , Inhibidores de Puntos de Control Inmunológico , Neoplasias Renales/tratamiento farmacológicoRESUMEN
Alimentary toxic aleukia (ATA) is correlated with consuming grains contaminated by Fusarium species, particularly T-2 toxin, which causes serious hurt to human and animal health, chiefly in disorders of the haematopoietic system. However, the mechanism of haematopoietic dysfunction induced by T-2 toxin and the possible target pathway for the treatment of T-2 toxin-induced haematopoietic disorder of ATA remains unclear. In this study, genomes and proteomics were used for the first time to investigate the key differential genes and proteins that inhibit erythroid differentiation of K562 cells caused by T-2 toxin, and it was found that heat shock protein 27 (HSP27) and membrane-spanning 4-domains, subfamily A, member 3 (MS4A3) may play an important role in erythroid differentiation. Meanwhile, MS4A3 interference can inhibit the occurrence of erythroid differentiation of K562 cells and promote the phosphorylation of HSP27. Moreover, the binding of HSP27 to MS4A3 in natural state can activate the phosphorylation site of HSP27 (Ser-83), while T-2 toxin can abolish the activation of phosphorylation site by inhibiting the expression of MS4A3. These findings for the first time demonstrated that the MS4A3-HSP27 pathway may function an efficient therapeutic target pathway for treating T-2 toxin elicited haematopoietic disorders of ATA.
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Proteínas de Choque Térmico HSP27 , Toxina T-2 , Animales , Humanos , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Toxina T-2/toxicidad , Fosforilación , Diferenciación Celular , Células K562 , Proteínas de la Membrana/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMEN
Icing phenomenon that occurs universally in nature and industry gets a great impact on human life. Over the past decades, extensive efforts have been made for a wide range of anti-icing/deicing surfaces, but the preparation of anti-icing/deicing interfaces that combine stability, rapid self-healing and excellent anti-icing/deicing performance remains a challenge. In this study, a photothermal solid slippery surface with excellent comprehensive performance is prepared by integrating cellulose acetate film, carbon nanotubes with paraffin wax (CCP). Apart from the excellent anti-icing and deicing properties at -17 ± 1.0 °C under 1 sun illumination, the surface can further achieve deicing at temperatures as low as -22 ± 1.0 °C under infrared light. The fabricated surface also exhibits great stability when placed in harsh conditions such as underwater or ultra-low temperature environments for over 30 days. Even when suffering from physical damage, the prepared surface can rapidly self-repair under 1 sun illumination or near-infrared (NIR) illumination within 16.0 ± 1.5 s. Due to the rapid and repeatable self-healing performance, the lubricating properties of the interface material do not deteriorate even after 50 repeated abrasing-repairing cycles. The photothermal solid slippery surface possesses wide-ranging applications and commercial value at high latitude and altitude regions.
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Nanotubos de Carbono , Humanos , Frío , Rayos Infrarrojos , Parafina , TemperaturaRESUMEN
Hydroquinone (HQ) is an important metabolites of benzene in the body, and it has been found to result in cellular DNA damage, mutation, cell cycle imbalance, and malignant transformation. The JNK1 signaling pathway plays an important role in DNA damage repair. In this study, we focused on whether the JNK1 signaling pathway is involved in the HQ-induced cell cycle abnormalities and the underlying mechanism. The results showed that HQ induced abnormal progression of the cell cycle and initiated the JNK1 signaling pathway. We further confirmed that JNK1 suppression decelerated the cell cycle progression through inhibiting pRb/E2F1 signaling pathway and triggering p53/p21 pathway. Therefore, we concluded that JNK1 might be involved in HQ-induced malignant transformation associated with activating pRb/E2F1 and inhibiting p53/p21 signaling pathway which resulting in accelerating the cell cycle progression.
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Hidroquinonas , Proteína p53 Supresora de Tumor , Proteína p53 Supresora de Tumor/metabolismo , Hidroquinonas/toxicidad , División Celular , Transducción de SeñalRESUMEN
Growth retardation is a global public health problem that is highly prevalent especially in low-and middle-income countries, which is closely related to the consumption of grains contaminated with T-2 toxin, a risk for human and animal health. However, the possible targets that can relieve T-2 toxin-induced growth retardation still need to be explored. In the present study, T-2 toxin was used as an environmental exposure factor to induce growth retardation and further explore the regulatory role of lncRNA in growth retardation. The present study systematically characterised the expression profiles of lncRNAs and identified a lncRNA lncMST that is related to growth retardation in T-2 toxin-administered rats. Functionally, lncMST could alleviate cell cycle arrest and apoptosis in T-2 toxin-treated GH3 cells. Mechanistically, lncMST, serve as an inducible chaperone RNA, involved in the paradigm "Chemical-induced stress related growth retardation", through recruiting the EPRS/HSP90AB1 complex to increase HDAC6 expression, thus further alleviating T-2 toxin-induced growth retardation. These findings for the first time demonstrate that the probable therapeutic relationship between lncMST and growth retardation, providing an explanation and therapeutic targets for the pathogenesis of growth retardation.
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ARN Largo no Codificante , Toxina T-2 , Humanos , Animales , Ratas , Toxina T-2/toxicidad , ARN Largo no Codificante/genética , Apoptosis , Exposición a Riesgos Ambientales , Trastornos del Crecimiento , Proteínas HSP90 de Choque Térmico/genéticaRESUMEN
Glaesserella parasuis (GPS), a causative agent of Glässer's disease, is thought to be the main fatal cause of peritonitis in swine, thus resulting in high mortality and morbidity and significant economic losses to the swine industry. However, the mechanisms of GPS infection-induced apoptosis and possible therapeutic pathway for GPS infection in peritonitis remain unclear. Baicalin has important biological functions during disease treatment, such as antiviral, bacterial inhibition, anti-apoptosis, and anti-inflammatory. However, whether baicalin has anti-apoptotic effects during the process of GPS infection in peritonitis is unclear. In the present study, the anti-apoptotic effect and mechanisms of baicalin in GPS infection-induced apoptosis were investigated in porcine peritoneal mesothelial cells (PPMC). The results showed that baicalin could inhibit the apoptosis rate occurrence of PPMC induced by GPS to various degrees and inhibit the expression of apoptosis-related genes and cleaved caspase-3. Meanwhile, baicalin significantly antagonized the expression of p-JNK, p-p38, and p-ERK induced by GPS in PPMC. These findings for the first time demonstrate that baicalin exerted the effect of antagonizing GPS induced apoptosis in PPMC by inhibiting the activation of the PKC-MAPK pathway and could be a therapeutic option in the management of GPS infection.
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Haemophilus parasuis , Peritonitis , Enfermedades de los Porcinos , Animales , Flavonoides/farmacología , Flavonoides/uso terapéutico , Peritonitis/tratamiento farmacológico , Porcinos , Enfermedades de los Porcinos/tratamiento farmacológicoRESUMEN
Obesity syndromes, characterized by abnormal lipid, cholesterol, and glucose metabolism, are detrimental to human health and cause many diseases, including obesity and type II diabetes. Increasing evidence has shown that long noncoding RNA (lncRNA), transcripts longer than 200 nucleotides that are not translated into proteins, play an important role in regulating abnormal metabolism in obesity syndromes. For the first time, we systematically summarize how lncRNA is involved in complex obesity metabolic syndromes, including the regulation of lipid, cholesterol, and glucose metabolism. Moreover, we discuss lncRNA involvement in food intake that mediates obesity syndromes. Furthermore, this review might shed new light on a lncRNA-based strategy for the prevention and treatment of obesity syndromes. Recent investigations support that lncRNA is a novel molecular target of obesity syndromes and should be emphasized. Namely, lncRNA plays a crucial role in the development of obesity syndrome process. Various lncRNAs are involved in the process of lipid, cholesterol, and glucose metabolism by regulating gene transcription, signaling pathway, and epigenetic modification of metabolism-related genes, proteins, and enzymes. Food intake could also induce abnormal expression of lncRNA associated with obesity syndrome, especially high-fat diet. Notably, some nanomolecules and natural extracts may target lncRNAs, associated with obesity syndrome, as a potential treatment for obesity syndromes.
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Obesidad , ARN Largo no Codificante , Colesterol/metabolismo , Glucosa/metabolismo , Humanos , Metabolismo de los Lípidos , Obesidad/genética , Obesidad/terapia , ARN Largo no Codificante/genéticaRESUMEN
A Gram-stain-positive, aerobic, non-motile, non-spore-forming and coccus-shaped strain, designated strain G463T, was isolated from the rhizosphere soil of Salicornia europaea L. collected from Lake Gudzhirganskoe in Siberia. Based on 16S rRNA gene phylogeny, strain G463T belonged to the genus Hoyosella, with the highest 16S rRNA gene sequence similarity to Hoyosella altamirensis DSM 45258T (96.1%). The major fatty acids were C17:1 ω8c, C16:0, C15 : 0 and C17:0. The strain contained meso-diaminopimelic acid as the cell-wall diagnostic diamino acid and arabinose, galactose and ribose as the whole-cell sugars. MK-8 and MK-7 were the predominant menaquinones. The polar lipid profile comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, one unidentified phosphoglycolipid, two unidentified glycolipids and several unidentified lipids. Acetyl was the muramyl residue. Mycolic acids (C28-C34) were present. The G+C content of the genomic DNA was 68.3 mol%. Based on its phylogenetic, phenotypic and chemotaxonomic features, strain G463T was considered to represent a novel species of the genus Hoyosella, for which the name Hoyosella lacisalsi sp. nov. is proposed. The type strain is G463T (=JCM 33650T=CGMCC 1.17230T).
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Lagos , Mycobacteriaceae/clasificación , Filogenia , Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano/genética , Ácidos Grasos/química , Lagos/microbiología , Mycobacteriaceae/aislamiento & purificación , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Siberia , Vitamina K 2/químicaRESUMEN
The majority of current drugs against diseases, such as cancer, can bind to one or more sites in a protein and inhibit its activity. There are, however, well-known limits on the number of druggable proteins, and complementary current drugs with compounds that could selectively target DNA or RNA would greatly enhance the availability of cellular probes and therapeutic progress. We are focusing on the design of sequence-specific DNA minor groove binders that, for example, target the promoter sites of transcription factors involved in a disease. We have started with AT-specific minor groove binders that are known to enter human cells and have entered clinical trials. To broaden the sequence-specific recognition of these compounds, several modules that have H-bond acceptors that strongly and specifically recognize G·C base pairs were identified. A lead module is a thiophene-N-alkyl-benzimidazole σ-hole-based system with terminal phenyl-amidines that have excellent affinity and selectivity for a G·C base pair in the minor groove. Efforts are now focused on optimizing this module. In this work, we are evaluating modifications to the compound aromatic system with the goal of improving GC selectivity and affinity. The lead compounds retain the thiophene-N-alkyl-BI module but have halogen substituents adjacent to an amidine group on the terminal phenyl-amidine. The optimum compounds must have strong affinity and specificity with a residence time of at least 100 s.
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Amidinas/química , Bencimidazoles/química , ADN/análisis , ADN/química , Tiofenos/química , Emparejamiento Base , Humanos , Estructura MolecularRESUMEN
A series of small diamidines with thiophene and modified N-alkylbenzimidazole σ-hole module represent specific binding to single Gâ C base pair (bp) DNA sequence. The variation of N-alkyl or aromatic rings were sensitive to microstructures of the DNA minor groove. Thirteen new compounds were synthesized to test their binding affinity and selectivity. The dicyanobenzimidazoles needed to synthesize the target diamidines were made via condensation/cyclization reactions of different aldehydes with different 3-amino-4-(alkyl- or phenyl-amino) benzonitriles. The final diamidines were synthesized using lithium bis-trimethylsilylamide (LiN[Si(CH3 )3 ]2 ) or Pinner methods. The newly synthesized compounds showed strong binding and selectivity to AAAGTTT compared to similar sequences AAATTT and AAAGCTTT investigated by several biophysical methods including biosensor-SPR, fluorescence spectroscopy, DNA thermal melting, ESI-MS spectrometry, circular dichroism, and molecular dynamics. The binding affinity results determined by fluorescence spectroscopy are in accordance with those obtained by biosensor-SPR. These small size single Gâ C bp highly specific binders extend the compound database for future biological applications.
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ADN/química , Pentamidina/química , Tiofenos/química , Emparejamiento Base , Técnicas Biosensibles/métodos , Dicroismo Circular , Espectrometría de FluorescenciaRESUMEN
Cyanine compounds have previously shown excellent in vitro and promising in vivo antileishmanial efficacy, but the potential toxicity of these agents is a concern. A series of 22 analogs of thiazole orange ((Z)-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium salt), a commercial cyanine dye with antileishmanial activity, were synthesized in an effort to increase the selectivity of such compounds while maintaining efficacy. Cyanines possessing substitutions on the quinolinium ring system displayed potency against Leishmania donovani axenic amastigotes that differed little from the parent compound (IC50 12-42â¯nM), while ring disjunction analogs were both less potent and less toxic. Changes in DNA melting temperature were modest when synthetic oligonucleotides were incubated with selected analogs (ΔTmâ¯≤â¯5⯰C), with ring disjunction analogs showing the least effect on this parameter. Despite the high antileishmanial potency of the target compounds, their toxicity and relatively flat SAR suggests that further information regarding the target(s) of these molecules is needed to aid their development as antileishmanials.
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Benzotiazoles/síntesis química , Leishmaniasis Visceral/metabolismo , Quinolinas/síntesis química , Animales , Descubrimiento de DrogasRESUMEN
Photocatalysis induced by sunlight is one of the most promising approaches to environmental protection, solar energy conversion, and sustainable production of fuels. The computational modeling of photocatalysis is a rapidly expanding field that requires to adapt and to further develop the available theoretical tools. The coupled transfer of protons and electrons is an important reaction during photocatalysis. In this work, we present the first step of our methodology development in which we apply the existing kinetic theory of such coupled transfer to a model system, namely, methanol photodissociation on the rutile TiO2(110) surface, with the help of high-level first-principles calculations. Moreover, we adapt the Stuchebrukhov-Hammes-Schiffer kinetic theory, where we use the Georgievskii-Stuchebrukhova vibronic coupling to calculate the rate constant of the proton coupled electron transfer reaction for a particular pathway. In particular, we propose a modified expression to calculate the rate constant, which enforces the near-resonance condition for the vibrational wave function during proton tunneling.
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BACKGROUND At present, the relationships among COVID-19 disease progression, patient prognosis, and immune status are unclear. This single-center retrospective study evaluated the correlation between serum interleukin-6 (IL-6) levels at admission with the severity of COVID-19 pneumonia, as determined by admission to the intensive Care Unit (ICU). MATERIAL AND METHODS Patients admitted to The First Affiliated Hospital of Bengbu Medical College in Bengbu City, Anhui Province, China, in January and February 2020 for COVID-19 pneumonia were enrolled in this study. COVID-19 infection was confirmed by the detection of SARS-CoV-2 nucleic acid in throat swab samples using real-time fluorescent reverse transcription PCR. Serum IL-6 concentrations at admission were measured by ELISA. Correlations between serum IL-6 concentrations and ICU admission due to the development of severe COVID-19 pneumonia were evaluated. RESULTS This study enrolled 68 patients with novel coronavirus pneumonia. IL-6 concentrations were significantly higher in patients with more severe than less severe COVID-19 pneumonia. Eight of 40 patients with severe COVID-19 pneumonia became critically ill and required ICU admission. IL-6 concentrations were significantly higher in patients with severe COVID-19 pneumonia who were than who were not treated in the ICU. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.816 (P<0.01), indicating that IL-6 was prognostic of disease severity in patients with COVID-19 pneumonia. CONCLUSIONS Serum IL-6 concentration is closely associated with the severity of COVID-19. Continuous monitoring of IL-6 has clinical value in evaluating patient condition.
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COVID-19/diagnóstico , Interleucina-6/sangre , SARS-CoV-2/inmunología , Adulto , Anciano , COVID-19/sangre , COVID-19/epidemiología , COVID-19/inmunología , China/epidemiología , Enfermedad Crítica/epidemiología , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Pandemias , Admisión del Paciente , Pronóstico , Curva ROC , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Malignant tumor endangers seriously the health of all mankind. Multidrug resistance (MDR) is one of the main causes of clinical tumor chemotherapy failure. Curcumin (CUR) has not only antitumor activity but also reversing tumor MDR effect. CUR reverses tumor MDR via regulating related signal pathways or corresponding expressed proteins or gene. When combined with chemotherapeutic agents, CUR can be a chemotherapeutic sensitive agent to enhance chemotherapy efficacy and weaken tumor MDR. On the other hand, to improve the MDR reversal effect of CUR, its derivatives have been extensively studied. Therefore, this article mainly focuses on reviewing the application of CUR and its derivatives in MDR and its mechanism of reversing MDR.
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Curcumina/análogos & derivados , Curcumina/uso terapéutico , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Curcumina/farmacología , Humanos , Neoplasias/patología , Fitoterapia , Transducción de Señal/efectos de los fármacosRESUMEN
Immunity imbalance and barrier damage in the intestinal mucosa are the main pathogenic factors of Crohn's disease (CD). Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES) is a glutaminase 1 (Gls1) inhibitor with the dual functions of increasing glutamine levels and immune regulation. In this study, we focused on the role of BPTES in CD-like enteritis and the possible mechanisms. We found that Gls1 expression was significantly increased in CD intestinal tissue compared with control tissue. Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide treatment significantly ameliorated chronic colitis in the IL-10-/- , as manifested by decreased disease activity index, body weight change, histological inflammatory degree and inflammatory cytokine expression. Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide treatment exerted protective effects on CD that were associated with the maintenance of intestinal barrier integrity and the Th/Treg balance. Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide treatment may act in part through TCR-mediated mammalian target of rapamycin complex 1 (mTORC1) signalling activation. In conclusion, inhibition of Gls1 expression attenuated chronic colitis by maintaining intestinal barrier integrity and the Th/Treg balance, thereby ameliorating CD-like colitis.