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Vanadate-based photocatalysts have recently attracted substantial attention owing to their outstanding photocatalytic activity for degrading organic pollutants and generating energy via photocatalytic processes. However, the relatively high price of vanadium has hindered the development of vanadate-based photocatalysts for various applications. Spent catalysts obtained from oil refineries typically contain a significant quantity of vanadium, making them valuable for recovery and utilization as precursors for the production of high-value-added photocatalysts. In this study, we transformed the V present in spent catalysts produced by the petrochemical industry into ternary vanadate-based photocatalysts [BiVO4/InVO4/Ag3VO4 (BVO/IVO/AVO, respectively)] designed for water remediation. The ternary composites revealed an enhanced photocatalytic capability, which was 1.42 and 5.1 times higher than those of the binary BVO/IVO and pristine AVO due to the facilitated charge separation. The ternary photocatalysts not only effectively treated wastewater containing various organic dyes, such as methylene blue (MB), rhodamine 6G (R6G), and brilliant green (BG), but also exhibited remarkable photocatalytic performance in the degradation of antibiotics, reduction of Cr(VI), and bacterial inactivation. This paper proposes a feasible route for recycling industrial waste as a source of vanadium to produce highly efficient vanadate-based photocatalysts.
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This work presents a hydrothermal method followed by a sonochemical treatment for synthesizing tantalum decorated on iron selenide (Ta/FeSe2) integrated with nitrogen-doped graphene (NGR) as a susceptible electrode material for detecting trolox (TRX) in berries samples. The surface morphology, structural characterizations, and electrochemical performances of the synthesized Ta/FeSe2/NGR composite were analyzed via spectrophotometric and voltammetry techniques. The GCE modified with Ta/FeSe2/NGR demonstrated an impressive linear range of 0.1 to 580.3 µM for TRX detection. Additionally, it achieved a remarkable limit of detection (LOD) of 0.059 µM, and it shows a high sensitivity of 2.266 µA µÐ-1 cm-2. Here, we used density functional theory (DFT) to investigate the structures of TRX and TRX quinone and the locations of energy levels and electron transfer sites. The developed sensor exhibits significant selectivity, satisfactory cyclic and storage stability, and notable reproducibility. Moreover, the practicality of TRX was assessed in different types of berries, yielding satisfactory recoveries.
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Cromanos , Frutas , Grafito , Nitrógeno , Tantalio , Grafito/química , Frutas/química , Nitrógeno/química , Tantalio/química , Cromanos/química , Cromanos/análisis , Teoría Funcional de la Densidad , Técnicas Electroquímicas , Límite de Detección , Electrodos , Hierro/química , Hierro/análisisRESUMEN
OBJECTIVES: Whether patients with infarct volume ≥150 mL could benefit from endovascular thrombectomy (EVT) remains unclear. METHODS: Patients (n=104) with anterior circulation Alberta Stroke Program Early Computed Tomography Score <6 were screened for infarct volume ≥150 mL using the Pullicino formula × (1-22%). The following were compared with the baseline at 90 days: the modified Rankin scale score (mRS) ≤3, mortality rate, symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours, and modified Thrombolysis in Cerebral Infarction (mTICI) ≥2b between the EVT and drug therapy (DT) groups. RESULTS: In patients with infarct volumes ≥150 mL, mRS≤3 at 90 days was higher in the EVT group than in the DT group [adjusted odds risk (aOR), 5.52; 95% CI: 1.10-28.24, P=0.04), and mTICI ≥2b at 82.8%. Intracranial hemorrhage within 48 hours occurred in 7 (24.1%) patients in the EVT group and 5 (14.7%) in the DT group (aOR, 0.75; 95% CI: 0.16-3.46; P=0.71). Older age (aOR, 0.94; 95% CI: 0.90-0.99, P=0.01), EVT treatment (aOR, 4.51; 95% CI: 1.60-12.78, P=0.01), and infarct volume ≥150 mL (aOR, 0.11; 95% CI: 0.04-0.31, P<0.01) were significantly associated with patient prognosis. CONCLUSIONS: Patients with infarct volume ≥150 mL who received EVT had a higher proportion of mRS≤3 compared with those who received DT. However, there was no statistically significant difference in intracranial hemorrhage and death between the groups. EVT, smaller infarct volume, and younger age were associated with a good prognosis. The findings require large sample data verification.
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The electronic structures, defect formations, defect transition levels and optical properties for VK+Hi defect models in KDP crystals have been studied based on DFT. Lattice dynamics methods give the most reasonable compensation mechanism for VK, namely compensation with the third-nearest Hi neighbor from VK for the paraelectric (PE) phase and compensation with the fourth-nearest neighbor Hi from VK for the ferroelectric (FE) phase. The defect formation energies indicate that the [Formula: see text] (The superscript represents the charged state, the 'x' represents neutral, ''' represents -1 charge state and '.' represents +1 charge state.) is the main defect type in this kind of defect cluster and a self-trapped electron is located at Hi in the (VK + Hi)' system. For [Formula: see text] system, one electron is accommodated in VK. There is not a new defect state in the band gap. The Hi bonds with the O ion (0.99 Å) form a hydroxyl. For (VK + Hi)' system, the hydroxyl is broken, the Hi exists in an atomic form and introduces new defect states in the band gap. As the large relaxation energy leads to a large Huang-Rhys factor, the Stokes red shifts will significantly affect the optical properties. A broad ultraviolet (UV) absorption band and emission band range from UV to visible are obtained originating from the defect cluster. We believe that the far-violet absorption peaks (167 nm and 179 nm) caused by defect cluster VK+Hi can significantly impact the optical damage threshold of the KDP.
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Na super ionic conductor (NASICON)-type polyanionic vanadium fluorophosphate Na3V2O2(PO4)2F (NVOPF) is a promising cathode material for high-energy sodium-ion batteries. The dynamic diffusion and exchange of sodium ions in the lattice of NVOPF are crucial for its electrochemical performance. However, standard characterizations are mostly focused on the as-synthesized material without cycling, which is different from the actual battery operation conditions. In this work, we investigated the hopping processes of sodium in NVOPF at the intermediate charging state with 23Na solid-state nuclear magnetic resonance (ssNMR) and density functional theory (DFT) calculations. Our experimental characterizations revealed six distinct sodium coordination sites in the intermediate structure and determined the exchange rates among these sites at variable temperatures. The theoretical calculations showed that these dynamic processes correspond to different ion transport pathways in the crystalline lattice. Our combined experimental and theoretical study uncovered the underlying mechanisms of the ion transport in cycled NVOPF and these understandings may help the optimization of cathode materials for sodium-ion batteries.
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Pesticides pollute natural water reservoirs through persistent accumulation. Therefore, their toxicity and degradability are serious issues. Carbendazim (CBZ) is a pesticide used against fungal infections in agricultural crops, and its overexploitation detrimentally affects aquatic ecosystems and organisms. It is necessary to design a logical, efficient, and field-deployable method for monitoring the amount of CBZ in environmental samples. Herein, a nano-engineered bismuth selenide (Bi2Se3)/functionalized carbon nanofiber (f-CNF) nanocomposite was utilized as an electrocatalyst to fabricate an electrochemical sensing platform for CBZ. Bi2Se3/f-CNF exhibited a substantial electroactive surface area, high electrocatalytic activity, and high conductivity owing to the synergistic interaction of Bi2Se3 with f-CNF. The structural chemical compositions and morphology of the Bi2Se3/f-CNF nanocomposite were confirmed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and field-emission scanning electron microscopy (FESEM). Electrochemical analysis was carried out using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The voltammetry and impedance experiments exposed that the Bi2Se3/f-CNF-modified GCE has attained adequate electrocatalytic function with amended features of electron transportation (Rct = 35.93 Ω) and improved reaction sites (0.082 cm2) accessible by CBZ moiety along with exemplary electrochemical stability (98.92%). The Bi2Se3/f-CNF nanocomposite exhibited higher sensitivity of 0.2974 µA µM-1cm-2 and a remarkably low limit of detection (LOD) of 1.04 nM at a broad linera range 0.001-100 µM. The practicability of the nanocomposite was tested in environmental (tap and pond water) samples, which supports excellent signal amplification with satisfactory recoveries. Hence, the Bi2Se3/f-CNF nanocomposite is a promising electrode modifier for detecting CBZ.
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Bencimidazoles , Bismuto , Carbamatos , Carbono , Nanofibras , Compuestos de Selenio , Carbono/química , Nanofibras/química , Ecosistema , Agua , Técnicas Electroquímicas/métodos , ElectrodosRESUMEN
BACKGROUND: Post-stroke depression (PSD) affects approximately one-third of stroke survivors, leading to adverse outcomes in rehabilitation, reduced quality of life, and increased mortality rates. Despite these implications, the underlying causes of PSD remain unclear, posing challenges for prevention and treatment. Echinacoside (ECH), a natural compound with known neuroprotective and antidepressant properties, holds significant therapeutic potential for PSD. However, the precise mechanism of its action remains unknown. PURPOSE: To unravel the specific mechanism through which ECH alleviates PSD by exploring the intricate interplay between ECH and Nrf2, as well as its impact on the BDNF/TrkB signaling axis. STUDY DESIGN AND METHODS: A rat PSD model was established though middle cerebral artery occlusion coupled with chronic unpredictable mild stress, followed by ECH treatment. The rats' depressive state was evaluated using the sucrose preference test and force swimming test. Brain damage was assessed through TTC staining, Nissl staining, and TUNEL assay. The multifaceted mechanism of ECH in PSD was investigated using immunofluorescence, immunohistochemistry, RT-qPCR, dual-luciferase assay, and western blotting. Additionally, the interaction between ECH and Nrf2 was explored through molecular docking and microscale thermophoresis. RESULTS: Our findings unveiled a novel facet of ECH action, demonstrating its unique ability to upregulate Nrf2 through acetylation within the hippocampus of PSD-affected rats (p < 0.05). Moreover, ECH showcased its distinctive potential by enhancing BDNF transcriptional activity, activating the BDNF/TrkB signaling axis, and orchestrating a comprehensive response against oxidative stress and apoptosis, thereby alleviating PSD symptoms in rats (p < 0.05). CONCLUSIONS: This study not only provides insights into the pivotal role of Nrf2 in mediating the BDNF/TrkB axis activation by ECH but also highlights the novelty of ECH's mechanism in addressing PSD. The elucidation of these unique aspects positions ECH as a groundbreaking candidate for further exploration and development in the realm of PSD intervention.
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Factor Neurotrófico Derivado del Encéfalo , Depresión , Glicósidos , Factor 2 Relacionado con NF-E2 , Ratas Sprague-Dawley , Transducción de Señal , Accidente Cerebrovascular , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Depresión/tratamiento farmacológico , Depresión/etiología , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Ratas , Glicósidos/farmacología , Acetilación , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Antidepresivos/farmacología , Simulación del Acoplamiento Molecular , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológicoRESUMEN
PURPOSE: Sunitinib is a recommended drug for metastatic renal cell carcinoma (RCC). However, the therapeutic potential of sunitinib is impaired by toxicity and resistance. Therefore, we seek to explore a combinatorial strategy to improve sunitinib efficacy of low-toxicity dose for better clinical application. METHODS: We screen synergistic reagents of sunitinib from a compound library containing 1374 FDA-approved drugs by in vitro cell viability evaluation. The synergistically antiproliferative and proapoptotic effects were demonstrated on in vitro and in vivo models. The molecular mechanism was investigated by phosphoproteomics, co-immunoprecipitation, immunofluorescence and western-blot assays, etc. RESULTS: From the four-step screening, nilotinib stood out as a potential synergistic killer combined with sunitinib. Subsequent functional evaluation demonstrated that nilotinib and sunitinib synergistically inhibit RCC cell proliferation and promote apoptosis in vitro and in vivo. Mechanistically, nilotinib activates E3-ligase HUWE1 and in combination with sunitinib renders MCL-1 for degradation via proteasome pathway, resulting in the release of Beclin-1 from MCL-1/Beclin-1 complex. Subsequently, Beclin-1 induces complete autophagy flux to promote antitumor effect. CONCLUSION: Our findings revealed that a novel mechanism that nilotinib in combination with sunitinib overcomes sunitinib resistance in RCC. Therefore, this novel rational combination regimen provides a promising therapeutic avenue for metastatic RCC and rationale for evaluating this combination clinically.
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Autofagia , Carcinoma de Células Renales , Resistencia a Antineoplásicos , Neoplasias Renales , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Pirimidinas , Sunitinib , Sunitinib/farmacología , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Humanos , Autofagia/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Línea Celular Tumoral , Animales , Pirimidinas/farmacología , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Ratones Desnudos , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Ratones Endogámicos BALB C , Proteolisis/efectos de los fármacos , Beclina-1/metabolismoRESUMEN
Diet modulates the rumen microbiota, which in turn can impact the animal performance. The rumen microbiota is increasingly recognized for its crucial role in regulating the growth and meat quality of the host. Nevertheless, the mechanism by which the rumen microbiome influences the fatty acid and amino acid profiles of lambs in the grass feeding system remains unclear. This study aimed to evaluate the effects of different native grass-based diets on animal performance, meat quality, fatty acid compositions, amino acid profiles, and rumen microbiota of lamb. Seventy-two Ujumqin lambs were randomly assigned into three treatments according to the initial body weight (27.39 ± 0.51 kg) and age (6 months ± 6 days). The lambs received three diets: (i) non-pelleted native grass hay with 40% concentrate diet; the native grass and concentrate were fed individually; (ii) pelleted native grass hay with 40% concentrate diet (PHLC); (iii) pelleted native grass hay with 60% concentrate diet (PHHC). The results showed that among the three groups, the PHHC and PHLC diets had markedly (P < 0.05) higher average daily gain and pH45 min, respectively. All amino acid levels were significantly (P < 0.05) decreased in the PHHC diet than in the PHLC diet. The principal coordinate analysis of the ruminal microbiota indicated the markedly distinct separation (P = 0.001) among the three groups. In addition, the correlation analysis showed that the Rikenellaceae_RC9_gut_group, Prevotellaceae_UCG-003, Succinivibrio, and Succiniclasticum were significantly (P < 0.05) associated with most of the fatty acid and amino acid profiles. The correlation analysis of the association of microbiome with the meat quality provides us with a comprehensive understanding of the composition and function of the rumen microbial community, and these findings will contribute to the direction of future research in lamb. IMPORTANCE: Diet modulates the gut microbiome, which in turn impact the meat quality, yet few studies investigate the correlation between the rumen microbiome and the fatty acid profile of meat. Here, the current study develops an experiment to investigate the correlation of the rumen microbiome and fatty acid profile of meat: rumen microbiome responses to feed type and meat quality. The results indicated a unique microbiota in the rumen of lamb in response to diets and meat quality. Associations between utilization and production were widely identified among the affected microbiome and meat quality, and these findings will contribute to the direction of future research in lamb.
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Microbioma Gastrointestinal , Rumen , Ovinos , Animales , Alimentación Animal/análisis , Dieta/veterinaria , Ácidos Grasos/metabolismo , Carne , Aminoácidos/metabolismoRESUMEN
Considering the opening of high-speed railway (HSR) as a quasi-natural experiment, this paper explores the emission reduction effect of HSR opening and its mechanisms and heterogeneity characteristics based on the panel data of 272 cities in China from 2006 to 2019 by staggered DID model and the mediating effect model. It is found that (1) the opening of HSR significantly reduces the carbon emission level of cities, and the conclusion still holds after controlling the endogeneity issue and a series of robustness tests; (2) Bancon decomposition and negative weight diagnostics both show that the estimated average treatment effect bias is small and the robust estimators are more robust; (3) by reducing production costs and promoting inter-regional industrial division of labor, the opening of HSR promotes intra-industrial structural transformation and inter-industrial structural transformation, respectively, thus reducing urban carbon emissions. At the same time, HSR achieves urban carbon emission reduction by promoting free movement of population and human capital agglomeration; and (4) further study finds that there is regional heterogeneity in the emission reduction effect of HSR opening, and the carbon reduction effect is mainly reflected in large and medium-sized cities, near provincial capitals, non-resource-based cities, and cities with rich educational resources, which indicates that the location of future HSR should be combined with the city's own characteristics and be tailored to the city.
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Carbono , Industrias , Humanos , China , Ciudades , Movimiento , Desarrollo EconómicoRESUMEN
For the first time, a tumour hypoxia marker detection has been developed using two-dimensional layered composite modified electrodes in biological and environmental samples. The concept of TaB2 and V4C3-based MXene composite materials is not reported hitherto using ball-milling and thermal methods and it remains the potentiality of the present work. The successful formation is confirmed through various characterisation techniques like X-ray crystallography, scanning electron microscopy photoelectron, and impedance spectroscopy. A reliable and repeatable electrochemical sensor based on TaB2@V4C3/SPCE was developed for quick and extremely sensitive detection of pimonidazole by various electroanalytical methods. It has been shown that the modified electrode intensifies the reduction peak current and causes a decrease in the potential for reduction, in comparison with the bare electrode. The proposed sensor for pimonidazole reduction has strong electrocatalytic activity and high sensitivity, as demonstrated by the cyclic voltammetry approach. Under the optimal experimental circumstances, differential pulse voltammetry techniques were utilised for generating the wide linear range (0.02 to 928.51 µM) with a detection limit of 0.0072 µM. The resultant data demonstrates that TaB2@V4C3/SPCE nano-sensor exhibits excellent stability, reliability, and repeatability in the determination of pimonidazole. Additionally, the suggested sensor was successfully used to determine the presence of pimonidazole in several real samples, such as human blood serum, urine, water, and drugs.
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Carbono , Nitroimidazoles , Tantalio , Humanos , Carbono/química , Vanadio , Reproducibilidad de los Resultados , Límite de Detección , Electrodos , Compuestos de BoroRESUMEN
BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) is a phenomenon that pathological injury of ischemic brain tissue is further aggravated after the restoration of blood supply. The complex pathological mechanism of CIRI has led to the failure of multiple neuroprotective agents in clinical studies. Salvianolic acid A (SAA) is a neuroprotective extract from Salvia miltiorrhiza Bge., with significant pharmacological activities in the treatment of brain injury. However, the neuroprotective mechanisms of SAA remain unclear. PURPOSE: To explore the potential protective effect of SAA on CIRI and its mechanism, and to provide experimental basis for the research of new drugs for CIRI. STUDY DESIGN: A model of transient middle cerebral artery occlusion (tMCAO) in rats was used to simulate clinical CIRI, and the neuroprotective effect of SAA on tMCAO rats was investigated within 14 days after reperfusion. The improvement effects of SAA on cognitive impairment of tMCAO rats were investigated by behavioral tests from days 7-14. Finally, the neuroprotective mechanism of SAA was investigated on day 14. METHODS: The neuroprotective effects and mechanism of SAA were investigated by behavioral tests, HE and TUNEL staining, RNA sequence (RNA-seq) analysis and Western blot in tMCAO rats. RESULTS: The brain protective effects of SAA were achieved by alleviating cerebral infarction, cerebral edema, cerebral atrophy and nerve injury in tMCAO rats. Meanwhile, SAA could effectively improve the cognitive impairment and pathological damage of hippocampal tissue, and inhibit cell apoptosis in tMCAO rats. Besides, SAA could provide neuroprotective effects by up-regulating the expression of Bcl-2, inhibiting the activation of Caspase 3, and regulating PKA/CREB/c-Fos signaling pathway. CONCLUSION: SAA can significantly improve brain injury and cognitive impairment in CIRI rats, and this neuroprotective effect may be achieved through the anti-apoptotic effect and the regulation of PKA/CREB/c-Fos signaling pathway.
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Lesiones Encefálicas , Isquemia Encefálica , Ácidos Cafeicos , Lactatos , Fármacos Neuroprotectores , Daño por Reperfusión , Ratas , Animales , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas Sprague-Dawley , Transducción de Señal , Isquemia Encefálica/patología , Daño por Reperfusión/metabolismo , Apoptosis , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Lesiones Encefálicas/tratamiento farmacológicoRESUMEN
Flexible laser-scribed graphene (LSG) substrates with gold nanoislands have been developed as biochips for in situ electrochemical (EC) and surface-enhanced Raman scattering (SERS) biodetection (biomolecules and viral proteins). A flexible biochip was fabricated using CO2 laser engraving polyimide (PI) films to form a 3D porous graphene-like nanostructure. Gold nanoislands were deposited on the LSG substrates to enhance the intensity of the Raman signals. Moreover, the addition of auxiliary and reference electrodes induced a dual-function EC-SERS biochip with significantly enhanced detection sensitivity. The biochip could selectively and easily capture SARS-CoV-2 S1 protein through the SARS-CoV-2 S1 antibody immobilized on EC-SERS substrates using 1-ethyl-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The grafted antibody specifically bound to SARS-CoV-2, resulting in a significant increase in the SERS signal of the target analyte. The limit of detection (LOD) of the SARS-CoV-2 S1 protein was 5 and 100 ng/mL by using EC and SERS detection, respectively. Although the LOD of the SARS-CoV-2 S1 protein detected using SERS is only 100 ng/mL, it can provide fingerprint information for identification. To improve the LOD, EC detection was integrated with SERS detection. The three-electrode detection chip enables the simultaneous detection of SERS and EC signals, which provides complementary information for target identification. The dual-functional detection technology demonstrated in this study has great potential for biomedical applications, such as the rapid and sensitive detection of SARS-CoV-2.
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Técnicas Biosensibles , COVID-19 , Grafito , Nanopartículas del Metal , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Anticuerpos , Oro , Espectrometría RamanRESUMEN
Na superionic conductor (NASICON)-type Na3(VO)2(PO4)2F (NVOPF) exhibits excellent cycling stability for high-voltage sodium ion batteries. Various strategies have been developed to form ion-exchanged NVOPF which can enhance the ionic and electronic conductivity. However, the underlying ion transport mechanism and complex structural transitions during battery operation remained uninvestigated. In this work, we prepared lithium-exchanged NVOPF (namely NLVOPF) which shows improved ionic conductivity and increased capacity at high discharging rates. Solid-state nuclear magnetic resonance (SSNMR) revealed the distinctive presence of two kinds of Li-exchanged sites in the NLVOPF, which are attributed to the occupied lithium ions at the Na1 and Na2 sites (namely Li1 and Li2, respectively). The Li1 site was metastably replaced in the first cycle, yet the Li2 site participated in ion insertion/extraction in the subsequent cycles. Our characterizations show that the dynamic doping of lithium in NLVOPF could contribute to the improved cycling stability and capacity retention.
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Gastric neoplasm is a high-mortality cancer worldwide. Chemoresistance is the obstacle against gastric cancer treatment. Mitochondrial dysfunction has been observed to promote malignant progression. However, the underlying mechanism is still unclear. The mitokine growth differentiation factor 15 (GDF15) is a significant biomarker for mitochondrial disorder and is activated by the integrated stress response (ISR) pathway. The serum level of GDF15 was found to be correlated with the poor prognosis of gastric cancer patients. In this study, we found that high GDF15 protein expression might increase disease recurrence in adjuvant chemotherapy-treated gastric cancer patients. Moreover, treatment with mitochondrial inhibitors, especially oligomycin (a complex V inhibitor) and salubrinal (an ISR activator), respectively, was found to upregulate GDF15 and enhance cisplatin insensitivity of human gastric cancer cells. Mechanistically, it was found that the activating transcription factor 4-C/EBP homologous protein pathway has a crucial function in the heightened manifestation of GDF15. In addition, reactive oxygen species-activated general control nonderepressible 2 mediates the oligomycin-induced ISR, and upregulates GDF15. The GDF15-glial cell-derived neurotrophic factor family receptor a-like-ISR-cystine/glutamate transporter-enhanced glutathione production was found to be involved in cisplatin resistance. These results suggest that mitochondrial dysfunction might enhance cisplatin insensitivity through GDF15 upregulation, and targeting mitokine GDF15-ISR regulation might be a strategy against cisplatin resistance of gastric cancer.
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Cisplatino , Neoplasias Gástricas , Humanos , Cisplatino/farmacología , Neoplasias Gástricas/patología , Regulación hacia Arriba , Factor 15 de Diferenciación de Crecimiento/genética , Factor 15 de Diferenciación de Crecimiento/metabolismo , OligomicinasRESUMEN
Upadacitinib has received approval for the treatment of atopic dermatitis (AD) with favorable response in clinical trials. However, real-world research on its efficacy remains relatively limited. To bridge this gap, we conducted a prospective cohort study involving 25 Chinese patients with moderate-to-severe AD. These patients received a daily dose of 15 mg of upadacitinib. Our objective was to assess the real-world efficacy of upadacitinib and its impact on the immune system. Clinical assessments were conducted at baseline, 4 weeks, 8 weeks, and 12 weeks following treatment initiation. The findings revealed that upadacitinib treatment significantly improved the clinical scores of the patients. Regarding immunological markers, upadacitinib led to a significant reduction in peripheral blood eosinophils, as well as a decrease in neutrophil count. Furthermore, upadacitinib treatment resulted in an overall decrease in Th1, Th2, and Th17/22-type cytokines, as well as other inflammatory factors. Importantly, for the first time, we observed a notable reduction in both IL-22+CD4+ T cells and serum IL-22 levels in all treated patients, including those with recalcitrant AD who had previously shown inadequate responses to systemic treatments like dupilumab. Currently, international guidelines position upadacitinib as a second-line option following the failure of systemic treatments like dupilumab. Our findings provide valuable insights into the real-world effectiveness and immunological impacts of upadacitinib, which can aid in better understanding and implementation of the drug in clinical practice.
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Dermatitis Atópica , Compuestos Heterocíclicos con 3 Anillos , Humanos , Dermatitis Atópica/tratamiento farmacológico , Pueblos del Este de Asia , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
In order to further clarify the effect of sulfur doping on the laser damage threshold of potassium dihydrogen phosphate (KDP), the properties of sulfur substituting for phosphorus doping defects (SP) in KDP crystals with paraelectric (PE) and ferroelectric (PE) phases are studied in this article. More accurate defect transition levels were obtained by band edge correction, and the band edge corrected values were 1.28 eV and 1.88 eV for the PE and FE phases, respectively. The defect formation energies with four different defect charges (0, +1, +2, and-1) were obtained using the finite size correction scheme. The stable defect charge states were (+2 charge state) (+1 charge state) and (-1 charge state) in turn when the Fermi level moved from the valence band maximum (VBM) to the conduction band minimum (CBM). Moreover, by considering the electron-phonon coupling, the optical absorption and emission spectra were obtained. The absorption peak for the state of the PE phase at 4.63 eV was close to the experimental value. We predicted that the absorption peak at 4.50 eV belongs to the state with the FE phase. The emission peaks at 0.10 eV and 1.36 eV were related to the PE and FE phases, accordingly. The absorption may affect the application of S-KDP crystals and reduce the laser damage threshold.
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Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.
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Gold (Au) nano-island arrays were deposited on the glass substrate to fabricate surface-enhanced Raman scattering (SERS) substrates by in-situ thermal evaporation (deposited and annealed samples at the same time). The optimal SERS intensity deposited by various thicknesses and in-situ annealing temperatures of Au nano-island arrays would be investigated. The biomolecules (adenine) were dropped on the well-designed SERS substrate for precise and quantitative SERS detection. The characterization of Au nano-island arrays SERS substrate would be evaluated by scanning electron microscope (SEM) and Raman spectroscopy. The results showed that the optimal deposition thickness and annealing temperature of Au nano-island arrays SERS substrate is about 14 nm and 200 °C respectively, which can construct the smallest interparticle spacing (W)/ particle diameter (D) ratio and the lowest reflection (%) and transmittance (%) to form the strongest SERS intensity. Moreover, finite-difference time-domain (FDTD) simulation of the electromagnetic field distributions on Au nano-island arrays displays the similar trend with the experimental results. The 14 nm deposition with 200 °C in-situ annealing temperature would display the highest density of hot-spots by FDTD simulation. The reproducible Au nano-island arrays SERS substrates with tunable surface roughness, W/D ratio, and lower reflection and transmittance show promising potential for SERS detection of biomolecules, bacteria, and viruses.