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The bifunctional oxygen electrocatalyst is the Achilles' heel of achieving robust reversible Zn-air batteries (ZABs). Herein, durable bifunctional oxygen electrocatalysis in alkaline media is realized on atomic Fe-N4-C sites reinforced by NixCo3-xO4 (NixCo3-xO4@Fe1/NC). Compared with that of pristine Fe1/NC, the stability of the oxygen evolution reaction (OER) is increased 10 times and the oxygen reduction reaction (ORR) performance is also improved. The steric hindrance alters the valence electron at the Fe-N4-C sites, resulting in a shorter Fe-N bond and enhanced stability of the Fe-N4-C sites. The corresponding solid-state ZABs exhibit an ultralong lifespan (>460 h at 5 mA cm-2) and high rate performance (from 2 to 50 mA cm-2). Furthermore, the structural evolution of NixCo3-xO4@Fe1/NC before and after the OER and ORR as well as charge-discharge cycling is explored. This work develops an efficient strategy for improving bifunctional oxygen electrocatalysis and possibly other processes.
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The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC50 value of 0.03 ± 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.
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Inhibidores Enzimáticos , Epóxido Hidrolasas , Animales , Benzamidas/farmacología , Benzamidas/uso terapéutico , Inhibidores Enzimáticos/química , Dolor , Ratas , Relación Estructura-Actividad , Urea/farmacología , Urea/uso terapéuticoRESUMEN
Methylpyridines are a class of highly toxic pyridine derivatives. In this study, a novel degrading bacterium was isolated for 3-methylpyridine (3-MP) degradation (Gordonia rubripertincta ZJJ, GenBank accession NO. OP430847.1; CCTCC M 2022975). The maximum specific degradation rate, half-saturation constant and inhibition constant were fitted to be 0.48 h-1, 88.3 mg L-1 and 924.0 mg L-1, respectively. During 3-MP biodegradation, the lost total organic carbon was transformed into CO2 (67.4 %) and biomass (32.6 %), and ammonia nitrogen was almost the sole inorganic species with a conversion rate of 36.3 %. Three metabolic pathways were possibly involved in 3-MP degradation: I) methyl oxidation followed by ring hydroxylation and hydrogenation; II) rupture of C=C and C-N bonds after ring reduction; III) initial ring hydroxylation. The study not only provides a novel strain for the high-efficient degradation of 3-MP, but also contributes to an in-depth understanding of 3-MP biotransformation.
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BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.
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It is an urgent need to improve the depth of discharge (DOD) of Zn-air batteries (ZABs), considering that most reported ZABs with long cycle life are realized at low DOD (<1%). In this work, our solid-state ZABs achieved a long cycle life of more than 220 h at 3.2% DOD (the discharge capacity of 10 mA h cm-2 per cycle). Moreover, benefiting from excellent bifunctional oxygen electrocatalysts (Fe@BNC) and robust Zn|electrolyte interface, the ZABs displayed a long cycle life of 120 h even at high DOD of 23.4% and large discharge capacity of 72 mA h cm-2. Additionally, the impact of Zn|electrolyte interface on the cycle time at different DODs is analysed and discussed. The unstable interface exacerbated the dendrite growth and uneven deposition of Zn at high DOD, leading to the decay of the cycle life. The work gives insights into the mechanism of the effect of DOD on the cycle life of the batteries.
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Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the pathogen of the Coronavirus disease-19 (COVID-19), is still devastating the world causing significant chaos to the international community and posing a significant threat to global health. Since the first outbreak in late 2019, several lines of intervention have been developed to prevent the spread of this virus. Nowadays, some vaccines have been approved and extensively administered. However, the fact that SARS-CoV-2 rapidly mutates makes the efficacy and safety of this approach constantly under debate. Therefore, antivirals are still needed to combat the infection of SARS-CoV-2. Papain-like protease (PLpro) of SARS-CoV-2 supports viral reproduction and suppresses the innate immune response of the host, which makes PLpro an attractive pharmaceutical target. Inhibition of PLpro could not only prevent viral replication but also restore the antiviral immunity of the host, resulting in the speedy recovery of the patient. In this review, we describe structural and functional features on PLpro of SARS-CoV-2 and the latest development in searching for PLpro inhibitors. Currently available inhibitors targeting PLpro as well as their structural basis are also summarized.
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To utilize intermittent renewable energy as well as achieve the goals of peak carbon dioxide emissions and carbon neutrality, various electrocatalytic devices have been developed. However, the electrocatalytic reactions, e.g., hydrogen evolution reaction/oxygen evolution reaction in overall water splitting, polysulfide conversion in lithium-sulfur batteries, formation/decomposition of lithium peroxide in lithium-oxygen batteries, and nitrate reduction reaction to degrade sewage, suffer from sluggish kinetics caused by multielectron transfer processes. Owing to the merits of accelerated charge transport, optimized adsorption/desorption of intermediates, raised conductivity, regulation of the reaction microenvironment, as well as ease to combine with geometric characteristics, the built-in electric field (BIEF) is expected to overcome the above problems. Here, we give a Review about the very recent progress of BIEF for efficient energy electrocatalysis. First, the construction strategies and the characterization methods (qualitative and quantitative analysis) of BIEF are summarized. Then, the up-to-date overviews of BIEF engineering in electrocatalysis, with attention on the electron structure optimization and reaction microenvironment modulation, are analyzed and discussed in detail. In the end, the challenges and perspectives of BIEF engineering are proposed. This Review gives a deep understanding on the design of electrocatalysts with BIEF for next-generation energy storage and electrocatalytic devices.
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Quasi-solid-state Zn-air batteries are usually limited to relatively low-rate ability (<10 mA cm-2), which is caused in part by sluggish oxygen electrocatalysis and unstable electrochemical interfaces. Here we present a high-rate and robust quasi-solid-state Zn-air battery enabled by atomically dispersed cobalt sites anchored on wrinkled nitrogen doped graphene as the air cathode and a polyacrylamide organohydrogel electrolyte with its hydrogen-bond network modified by the addition of dimethyl sulfoxide. This design enables a cycling current density of 100 mA cm-2 over 50 h at 25 °C. A low-temperature cycling stability of over 300 h (at 0.5 mA cm-2) with over 90% capacity retention at -60 °C and a broad temperature adaptability (-60 to 60 °C) are also demonstrated.
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Because of their high energy density, low cost, and environmental friendliness, lithium-sulfur (Li-S) batteries are one of the potential candidates for the next-generation energy-storage devices. However, they have been troubled by sluggish reaction kinetics for the insoluble Li2S product and capacity degradation because of the severe shuttle effect of polysulfides. These problems have been overcome by introducing transition metal compounds (TMCs) as catalysts into the interlayer of modified separator or sulfur host. This review first introduces the mechanism of sulfur redox reactions. The methods for studying TMC catalysts in Li-S batteries are provided. Then, the recent advances of TMCs (such as metal oxides, metal sulfides, metal selenides, metal nitrides, metal phosphides, metal carbides, metal borides, and heterostructures) as catalysts and some helpful design and modulation strategies in Li-S batteries are highlighted and summarized. At last, future opportunities toward TMC catalysts in Li-S batteries are presented.
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Salidroside (Sal) exerted widely pharmacological effects in multitudinous diseases had been certified. The actual study clarified the protective activity of Sal in H2O2-injured human trabecular meshwork (HTM) cells. HTM cells were disposed with H2O2 to construct an oxidative damage model in vitro. Then, Sal was utilized to administrate HTM cells, and cell viability, apoptosis, apoptosis-interrelated proteins and ROS production were appraised using CCK-8, flow cytometry, western blot and DCFH-DA staining. MiR-27a inhibitor and its control were transfected into HTM cells, and the influences of miR-27a inhibition in HTM cells stimulated with H2O2 and Sal were detected. PI3K/AKT and Wnt/ß-catenin pathways were ultimately investigated to uncover the underlying mechanism. We found that H2O2 evoked HTM cells oxidative damage, as evidenced by repressing cell viability, inducing apoptosis, activating cleaved-caspase-3/-9 expression and increasing ROS production. Sal significantly lightened H2O2-evoked oxidative damage in HTM cells. Additionally, miR-27a was up-regulated by Sal, and miR-27a suppression significantly reversed the protective effect of Sal on H2O2-injured HTM cells. Finally, Sal activated PI3K/AKT and Wnt/ß-catenin pathways through enhancement of miR-27a in H2O2-injured HTM cells. In conclusion, these discoveries suggested that Sal could protect HTM cells against H2O2-evoked oxidative damage by activating PI3K/AKT and Wnt/ß-catenin pathways through enhancement of miR-27a. Highlights H2O2 evokes HTM cells oxidative damage; Sal relieves H2O2-induced oxidative damage in HTM cells; Sal enhances miR-27a expression in H2O2-injured HTM cells; Repressed miR-27a reverses the protective impacts of Sal on H2O2-injured HTM cells; Sal activates PI3K/AKT and Wnt/ß-catenin pathways by increasing miR-27a.
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Glucósidos/farmacología , Peróxido de Hidrógeno/farmacología , MicroARNs/genética , Fenoles/farmacología , Malla Trabecular/citología , Malla Trabecular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Citoprotección/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Estrés Oxidativo/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Malla Trabecular/metabolismo , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Objective To develop a set of methods of amplifying the natural paring heavy and light chain genes from one single B cell. Methods Yanhuang (YH) cells were the first whole genome sequenced human cells of Asian origin. With the immortalized cell lines as the raw material, single CD19+ B cells were sorted into individual PCR tubes by fluorescence-activated cell sorting (FACS). Then its total RNA was released by the lysis buffer, and reverse transcribed. With the cDNA as the templates, the pairing heavy and light chains from the same B cells were amplified by two-step nested PCRs to acquire their variable region sequences. Results Amplifying methodology has been successfully developed for acquiring single cell BCR genes, and the success rate was greater than 80%. The sorted single B cells could be saved in -80DegreesCelsius for up to two weeks, and then successfully amplified. The PCR products in the same tube were TA-cloned and identified by Sanger sequencing, including the heavy and light chain pairing information. A set of effective primers were reported and released in this study. Conclusion A set of methods were successfully developed for amplifying the natural paring heavy and light genes with the beginning of one single B cell.
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Anticuerpos Monoclonales/genética , Linfocitos B , Reacción en Cadena de la Polimerasa , Línea Celular , Clonación Molecular , Cartilla de ADN , Citometría de Flujo , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Ligeras de Inmunoglobulina/genéticaRESUMEN
Advanced glycation end products (AGEs) plays an important role in diabetic embryopathy. AGE-mediated DNA damage could be a significant factor in the teratogenicity. The aim of the present study was to evaluate the association between the AGEs level and neural tube defects (NTDs) occurrence risk. Forty-eight mothers with NTD-affected pregnancies and 50 normal mothers were selected in this study. Blood were collected from the mothers and were assayed for serum AGEs, malondiadehyde (MDA) and hemoglobin A1c (HbA1c). Data were analyzed by logistic regression method. The study indicated that there were significant but modest lower prevalence for cases mothers on age, BMI and glucose levels compared with controls. NTD-affected mothers were significantly more likely to have higher AGEs levels (5.6±0.48 AU vs. 4.6±0.68 AU ρ<0.01) than controls. The AGEs levels were not correlated with MDA and HbA1c in NTDs mothers (r(2)=0.0006 p=0.8691 and r(2)=0.001 p=0.8172, respectively). The conclusion is that AGEs might be associated with NTDs occurrence.