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1.
Artículo en Inglés | MEDLINE | ID: mdl-38940780

RESUMEN

Context: Traumatic brain injury (TBI) can result in lifelong cognitive, emotional, and motor impairments. The emergency department is the first stop for diagnosing and treating patients with acute TBI, and the quality of nursing care can greatly influence the prognosis and progression of a patient's condition. Currently, standardized evaluation tools are lacking in the world for assessment of the quality of nursing care. Objective: The study intended to construct a nursing-sensitive indicator system for TBI patients, based on the scientific method of evidence-based nursing and the Delphi method, to provide a quantitative tool for emergency-nursing personnel to manage the quality of care for those patients. Design: Based on the Joanna Briggs Institute's evidence-based healthcare model, the research team performed a literature search and consulted reference guidelines, conducted two rounds of consultations with experts. sensitive indicators for quality of care, and constructed the sensitive indicator system. The team then conducted a retrospective study. Setting: The study took place in the department of emergency surgery at Shanxi Norman Bethune Hospital in Taiyuan, Shanxi, China. Participants: Participants were 56 patients with TBI who had been admitted to the emergency department between January 2022 and December 2022 and 44 patients with TBI who had been admitted to the emergency department between January 2023 and December 2023. Interventions: The research team assigned: (1) the 56 patients in the first group to the control group, who received routine nursing care and (2) the 44 patients in the second group to the intervention group, who received treatment using the sensitive indicator system for the quality of emergency care for TBI patients as well as routine care. Outcome Measures: In the verification study, the research team compared the group's rescue effects and satisfaction with emergency care. Results: In the first and second rounds of inquiries to experts, the research team distributed 25 questionnaires each time, with 25 valid questionnaires collected both times. The response rate for both rounds of inquiries was 100%. The expert authority coefficients for the first and second rounds of inquiries are 0.844 and 0.878, respectively. The sensitive indicator system's final construction included three primary indicators, seven secondary indicators, and 17 tertiary indicators. The AUC for the sensitive indicators was 0.8355882. The indicator system's use found that the intervention group had a shorter time to diagnosis (P < .001), emergency-department stay (P < .001), and emergency-department-to-surgery time (P < .001) compared to the control group. The intervention group also has a higher success rate for the emergency treatment (P = .014) and a higher nursing satisfaction with nurse-patient communications (P = .003), first-aid operations (P < .001), nursing attitudes (P < .001), and emergency environment (P < .001) compared to the control group. Conclusions: The process of constructing quality-sensitive indicators for the nursing care of TBI patients was scientific. The constructed quality-sensitive indicator system for the care of patients with TBI covers key factors that influence the quality of care. It's highly practical and has the ability to transform certain indicators, which can better guide the management of quality of care for TBI.

2.
Brain Res ; 1837: 148973, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38685372

RESUMEN

Methamphetamine (MA), a representative amphetamine-type stimulant, is one of the most abused drugs worldwide. Studies have shown that MA-induced neurotoxicity is strongly associated with oxidative stress and apoptosis. While nuclear factor E2-related factor 2 (Nrf2), an antioxidant transcription factor, is known to exert neuroprotective effects, its role in MA-induced dopaminergic neuronal apoptosis remains incompletely understood. In the present study, we explored the effects of MA on the expression levels of Nrf2, dynamin-related protein 1 (Drp1), mitofusin 1 (Mfn1), cytochrome c oxidase (Cyt-c), and cysteine aspartate-specific protease 3 (Caspase 3), as well as the correlations between Nrf2 and mitochondrial dynamics and apoptosis. Brain tissue from MA abusers was collected during autopsy procedures. An MA-dependent rat model was also established by intraperitoneal administration of MA (10 mg/kg daily) for 28 consecutive days, followed by conditioned place preference (CPP) testing. Based on immunohistochemical staining and western blot analysis, the protein expression levels of Nrf2 and Mfn1 showed a decreasing trend, while levels of Drp1, Cyt-c, and Caspase 3 showed an increasing trend in the cerebral prefrontal cortex of both MA abusers and MA-dependent rats. Notably, the expression of Nrf2 was positively associated with the expression of Mfn1, but negatively associated with the expression levels of Drp1, Cyt-c, and Caspase 3. These findings suggest that oxidative stress and mitochondrial fission contribute to neuronal apoptosis, with Nrf2 potentially playing a critical role in MA-induced neurotoxicity.


Asunto(s)
Apoptosis , Metanfetamina , Dinámicas Mitocondriales , Factor 2 Relacionado con NF-E2 , Corteza Prefrontal , Animales , Metanfetamina/farmacología , Metanfetamina/toxicidad , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Dinámicas Mitocondriales/fisiología , Dinámicas Mitocondriales/efectos de los fármacos , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Factor 2 Relacionado con NF-E2/metabolismo , Masculino , Ratas , Humanos , Adulto , Ratas Sprague-Dawley , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Dinaminas/metabolismo , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/toxicidad , Trastornos Relacionados con Anfetaminas/metabolismo , Trastornos Relacionados con Anfetaminas/patología , Persona de Mediana Edad , Adulto Joven , Femenino
3.
Talanta ; 275: 126064, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38640519

RESUMEN

Chinese Baijiu (Liquor) is a popular alcoholic beverage, and the ethanol content in Baijiu is closely related to its quality; therefore, it is of great significance to explore a facile, sensitive, and rapid method to detect ethanol content in Baijiu. Hydrophobic carbon quantum dots (H-CQDs) with bright red fluorescence (24.14 %) were fabricated by hydrothermal method using o-phenylenediamine, p-aminobenzoic acid, manganese chloride, and hydrochloric acid as reaction precursors. After the introduction of ultrapure water into the ethanol solution dissolved with H-CQDs, the aggregated H-CQDs resulted in significant changes in fluorescence intensity and absorbance. On this basis, a sensor for detecting ethanol by optical dual-mode and smartphone imaging was constructed. More importantly, the sensor can be used for detecting ethanol content in Chinese Baijiu with satisfactory results. This sensing platform has great potential for quality identification in Chinese Baijiu, broadening the application scope of CQDs in food safety detection.


Asunto(s)
Bebidas Alcohólicas , Carbono , Interacciones Hidrofóbicas e Hidrofílicas , Puntos Cuánticos , Teléfono Inteligente , Puntos Cuánticos/química , Carbono/química , Bebidas Alcohólicas/análisis , Etanol/química , Etanol/análisis , Fluorescencia , Espectrometría de Fluorescencia/métodos
4.
bioRxiv ; 2024 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-38260351

RESUMEN

Single cell lineage tracing, essential for unraveling cellular dynamics in disease evolution is critical for developing targeted therapies. CRISPR-Cas9, known for inducing permanent and cumulative mutations, is a cornerstone in lineage tracing. The novel homing guide RNA (hgRNA) technology enhances this by enabling dynamic retargeting and facilitating ongoing genetic modifications. Charting these mutations, especially through successive hgRNA edits, poses a significant challenge. Our solution, LINEMAP, is a computational framework designed to trace and map these mutations with precision. LINEMAP meticulously discerns mutation alleles at single-cell resolution and maps their complex interrelationships through a mutation evolution network. By utilizing a Markov Process model, we can predict mutation transition probabilities, revealing potential mutational routes and pathways. Our reconstruction algorithm, anchored in the Markov model's attributes, reconstructs cellular lineage pathways, shedding light on the cell's evolutionary journey to the minutiae of single-cell division. Our findings reveal an intricate network of mutation evolution paired with a predictive Markov model, advancing our capability to reconstruct single-cell lineage via hgRNA. This has substantial implications for advancing our understanding of biological mechanisms and propelling medical research forward.

5.
Int J Toxicol ; 43(2): 165-176, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38006258

RESUMEN

Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to neurotoxicity and drug addiction. Studies have shown that neurotoxicity is strongly associated with METH-induced neuroinflammation, and microglia are the key drivers of neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) is reported to play a key role in activation of microglia and neuroinflammation. Yet, the molecular mechanisms by which METH causes neuroinflammation and neurotoxicity remain elusive. In the current study, we investigated the role of TREM2 in neuroinflammation induced by METH in BV2 cells and the wild-type (WT) C57BL/6J mice, CX3CR1GFP/+ transgenic mice, and TREM2 knockout (KO) mice. Postmortem samples from the frontal cortex of humans with a history of METH use were also analyzed to determine the levels of TREM2, TLR4, IBA1, and IL-1ß. The expression levels of TREM2, TLR4, IBA1, IL-1ß, iNOS, and Arg-1 were then assessed in the BV2 cells and frontal cortex of mice and human METH users. Results revealed that the expression levels of TREM2, TLR4, IBA1, and IL-1ß were significantly elevated in METH-using individuals and BV2 cells. Microglia were clearly activated in the frontal cortex of WT C57BL/6 mice and CX3CR1GFP/+ transgenic mice, and the protein levels of IBA1, TREM2, TLR4, and IL-1ß were elevated in the METH-induced mouse models. Moreover, TREM2-KO mice showed further increased microglial activation, neuroinflammation, and excitotoxicity induced by METH. Thus, these findings suggest that TREM2 may be a target for regulating METH-induced neuroinflammation.


Asunto(s)
Metanfetamina , Humanos , Animales , Ratones , Metanfetamina/toxicidad , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Receptor Toll-Like 4/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , Células Mieloides/metabolismo
6.
Hum Exp Toxicol ; 42: 9603271231219488, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38031934

RESUMEN

OBJECTIVES: Methamphetamine (MA) abuse is a serious social problem worldwide. Cardiovascular complications were the second leading cause of death among MA abusers. We aimed to clarify the effects of MA on myocardial injury, oxidative stress, and apoptosis in myocardial cells and to explore the potential mechanism of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in MA-induced oxidative stress and apoptosis. METHODS: An acute cardiac toxicity model of MA was established by intraperitoneal injection of MA (2 mg/kg) for 5 days. Nrf2 activation (by sulforaphane (SFN) 1 h before MA injection) and Nrf2 gene knockout were performed to explore the regulatory effects of Nrf2 on cardiac toxicity. RESULTS: The protein expressions of Nrf2 (p < .001) and heme oxygenase-1 (HO-1) were increased (p < .01), suggesting that MA activated the Nrf2/HO-1 pathway. In the MA group, cardiac injury score (p < .001) and cardiac troponin I (cTnI) protein expression increased (p < .01). Malondialdehyde (MDA) content increased (p < .001), superoxide dismutase (SOD) activity decreased (p < .05). Protein expressions of Caspase-3 (p < .001) and Bax (p < .001) increased, and Bcl-2 decreased (p < .001) as well. These changes were reversed by activation of Nrf2 but became more pronounced after Nrf2 knockout, suggested that the activation and knockout of Nrf2 attenuated and aggravated MA-induced myocardial injury, oxidative stress and apoptosis in myocardial cells, respectively. CONCLUSIONS: MA administration induced myocardial injury, oxidative stress, and apoptosis in mice. Nrf2 attenuated MA-induced myocardial injury by regulating oxidative stress and apoptosis, thus playing a protective role.


Asunto(s)
Cardiotoxicidad , Metanfetamina , Factor 2 Relacionado con NF-E2 , Animales , Ratones , Apoptosis , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Metanfetamina/toxicidad , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Transducción de Señal
7.
Adv Sci (Weinh) ; 10(30): e2302703, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37697645

RESUMEN

Single-atom nanozymes (SAzymes) with high catalytic activity exhibit the potential to disequilibrate the reactive oxygen metabolic balance in the tumor microenvironment (TME), which contains several endogenous reductive substances such as glutathione (GSH). Herein, a novel nano-assembly (CDs@Pt SAs/NCs@DOX) is first constructed using drug-primed platinum (Pt) single-atom or nanocluster nanozymes with a Pt loading of 34.8%, which exhibits prominent dual enzymatic activities to mimic peroxidase (POD) and glutathione oxidase (GSHOx). The unique GSHOx-like activity can efficiently scavenge GSH with a relatively low Km (1.04 mm) and high Vmax (7.46 × 10-6  m s-1 ), thus avoiding single oxygen (1 O2 ) depletion. CDs@Pt SAs/NCs@DOX simultaneously demonstrates low-temperature photothermal therapy and TME- or laser-controlled disassembly and drug release, which can effectively regulate cellular redox homeostasis and achieve high tumor growth inhibition. These outcomes may provide promising strategies for the preparation of Pt SAzymes with multiple activities and variable-sized nano-assemblies, allowing for broader applications of SAzymes and nano-assemblies in the biomedical field.


Asunto(s)
Neoplasias , Platino (Metal) , Humanos , Homeostasis , Neoplasias/tratamiento farmacológico , Glutatión , Oxígeno , Oxidación-Reducción , Microambiente Tumoral
8.
Toxicol Lett ; 384: 136-148, 2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37567421

RESUMEN

Methamphetamine (MA) is a widely abused drug that can cause kidney damage. However, the molecular mechanism remains unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates resistance to oxidative and proteotoxic stress. In this study, we investigated the role of Nrf2 in MA-induced renal injury in mice. Nrf2 was pharmacologically activated and genetically knocked-out in mice. The animal model of MA-induced nephrotoxicity was established by injecting MA (2 mg/kg) intraperitoneally twice a day for 5 days. Histopathological alterations were shown in the MA-exposed kidneys. MA significantly increased renal function biomarkers and kidney injury molecule-1 (KIM-1) levels. MA decreased superoxide dismutase activity and increased malondialdehyde levels. Autophagy-related factors (LC3 and Beclin 1) were elevated in MA-treated mice. Furthermore, Nrf2 increased in the MA-exposed kidneys. Activation of Nrf2 may attenuate histopathological changes in the kidneys of MA-treated mice. Pre-administration of Nrf2 agonist significantly decreased KIM-1 expression, oxidative stress, and autophagy in the kidneys after MA toxicity. In contrast, Nrf2 knockout mice treated with MA lost renal tubular morphology. Nrf2 deficiency increased KIM-1 expression, oxidative stress, and autophagy in the MA-exposed kidneys. Our results demonstrate that Nrf2 may protect against MA-induced nephrotoxicity by mitigating oxidative stress and autophagy.


Asunto(s)
Enfermedades Renales , Factor 2 Relacionado con NF-E2 , Animales , Ratones , Autofagia , Riñón/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Enfermedades Renales/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/fisiología , Metanfetamina/toxicidad
9.
Dalton Trans ; 52(19): 6551-6558, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37185994

RESUMEN

Carbon dots are popular luminescent materials because of their excellent fluorescence properties, but the low quantum yield limits their application. Heteroatom doping is a more convenient and popular approach to increase the quantum yield of carbon dots. Here, novel N,S,P heteroatom co-doped carbon dots (N,S,P-CDs) were synthesized by a simple one-step hydrothermal method using m-phenylenediamine, L-cysteine and phosphoric acid as raw materials. The as-prepared N,S,P-CDs showed excellent photoluminescence properties with a fluorescence quantum yield of up to 41%, which greatly encourages their application in fluorescence sensing. The N,S,P-CDs exhibited good fluorescence stability under salt solution, xenon lamp irradiation and ultraviolet lamp irradiation except for a high sensitivity to extreme acidity. The fluorescence intensity of the N,S,P-CDs can be decreased by as much as 85% when the pH of the solution changes from 2.50 to 4.75, that is, a small fluctuation in pH can cause an intense response of the fluorescence of the N,S,P-CDs. Therefore, an excellent fluorescence sensing platform for accurately monitoring the pH of extreme acidity has been constructed. In addition, the N,S,P-CDs can be applied for quantitative detection of folic acid based on the strong quenching effect of folic acid on the fluorescence of the N,S,P-CDs. Good linearity was obtained in the concentration range of 4.85-82.45 µM, with a detection limit of 0.148 µM. The constructed sensing platform was used for the determination of folic acid in actual samples of orange juice, oatmeal and tablets with satisfactory results.

10.
Nat Commun ; 14(1): 1936, 2023 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-37024459

RESUMEN

Serine proteases (SP), including furin, trypsin, and TMPRSS2 cleave the SARS-CoV-2 spike (S) protein, enabling the virus to enter cells. Here, we show that factor (F) Xa, an SP involved in blood coagulation, is upregulated in COVID-19 patients. In contrast to other SPs, FXa exerts antiviral activity. Mechanistically, FXa cleaves S protein, preventing its binding to ACE2, and thus blocking viral entry and infection. However, FXa is less effective against variants carrying the D614G mutation common in all pandemic variants. The anticoagulant rivaroxaban, a direct FXa inhibitor, inhibits FXa-mediated S protein cleavage and facilitates viral entry, whereas the indirect FXa inhibitor fondaparinux does not. In the lethal SARS-CoV-2 K18-hACE2 model, FXa prolongs survival yet its combination with rivaroxaban but not fondaparinux abrogates that protection. These results identify both a previously unknown function for FXa and an associated antiviral host defense mechanism against SARS-CoV-2 and suggest caution in considering direct FXa inhibitors for preventing or treating thrombotic complications in COVID-19 patients.


Asunto(s)
COVID-19 , Factor Xa , Humanos , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Rivaroxabán/farmacología , Rivaroxabán/uso terapéutico , SARS-CoV-2/metabolismo , Internalización del Virus , Antivirales/farmacología
11.
Int J Mol Sci ; 24(2)2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36674556

RESUMEN

The modification of chitosan (CS) has greatly expanded its application in the field of medicine. In this study, low-molecular-weight chitosan was modified with arginine (Arg) by a simple method. The identification by the Fourier transform infrared spectra (FTIR) showed that Arg was successfully covalently attached to the CS. Interestingly, Arg-CS was identified as nanoparticles by atomic force microscopy (AFM) and transmission electron microscopy (TEM), whose particle size was 75.76 ± 12.07 nm based on Dynamic Light Scattering (DLS) characterization. Then, whether the prepared Arg-CS nanoparticles could encapsulate and deliver siRNA safely was investigated. Arg-CS was found to be able to encapsulate siRNAs in vitro via electrostatic interaction with siRNA; the Arg-CS/siRNA complex was safe for L1210 leukemia cells. Therefore, modification of chitosan by Arg produces novel nanoparticles to deliver siRNA into leukemia cells. This is the first time to identify Arg-CS as nanoparticles and explore their ability to deliver Rhoa siRNA into T-cell acute lymphoblastic leukemia (T-ALL) cells to advance therapies targeting Rhoa in the future.


Asunto(s)
Quitosano , Leucemia , Nanopartículas , Animales , Ratones , ARN Interferente Pequeño/genética , Arginina , Leucemia/genética , Leucemia/terapia , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier
12.
J Hazard Mater ; 445: 130456, 2023 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-36450190

RESUMEN

Developing carbon quantum dots (CQDs) with the solvatochromic effect and exploring multifunctional applications remains challenging. Herein, robust solvatochromic carbon quantum dots (RS-CQDs) with emission shift up to ∼62 nm from yellow to red was fabricated by the hydrothermal method. The RS-CQDs was used to detect water and Sn4+ in the linear ranges and limits of detection of 2.0-97.6% and 0.14% and 6.24-53.18 µM and 66.3 nM, respectively, and was further applied to determine Sn4+ in practical water samples with satisfactory results. In addition, RS-CQDs exhibited bright red emission in oil media with a 9.7-fold increase in fluorescence relative to aqueous media, making them a wash-free probe for specifically staining lipids. Compared to the commercial lipid marker BODIPY 493/503, the RS-CQDs-based probe has significant advantages, such as longer emission, larger Stokes shift, and better photostability, ensuring that RS-CQDs-based marker can implement real-time and wash-free monitoring and imaging of lipids in living cells, liver tissues, zebrafish embryos, and zebrafish larvae. This study provides a novel research direction for the development of metal-doped CQDs by demonstrating RS-CQDs as the viability of fluorescence probes for water and Sn4+ detection and the efficiency of RS-CQDs as a fluorescent marker for lipid imaging.


Asunto(s)
Puntos Cuánticos , Animales , Puntos Cuánticos/toxicidad , Agua , Pez Cebra , Carbono , Colorantes Fluorescentes , Lípidos
13.
Ann Transl Med ; 10(18): 985, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36267753

RESUMEN

Background: Methamphetamine (MA) abuse is a major global public health problem. However, it is not yet known whether cannabidiol (CBD) has protective effects on MA-induced cardiotoxicity. The present study investigated whether CBD has protective effects on MA-induced cardiac damage in rats via the protein kinase A/cyclic adenosine monophosphate (cAMP)-response element-binding protein (PKA/CREB) pathway. Methods: A total of 30 rats were randomly divided into 5 groups. The rats were administered MA (10 mg/kg) by intraperitoneal (IP) injection once a day for 4 weeks, and with CBD (40 or 80 mg/kg, IP) treatment 1 h before the MA injections. Morphological changes were determined using hematoxylin and eosin and Masson's trichrome staining. The serum levels of interleukin (IL)-6 and IL-10 were detected using enzyme-linked immunoassay kits. The protein expression levels of cardiac troponin I (cTnI), PKA, phospho-PKA (p-PKA), CREB, and phospho-CREB (p-CREB) in the myocardium were detected by Western blot analysis. Results: There was no significant difference in body weight among the groups. Heart weight and the heart-to-body weight ratio were higher in the MA group than the control group, while CBD (80 mg/kg) pretreatment (CBD80 + MA group) reduced the heart weight and the heart-to-body weight ratio compared to the MA group. The chronic administration of MA resulted in a cardiac inflammatory response, the progressive development of fibrosis, and necrosis, while CBD treatment attenuated these lesions. The protein expression levels of PKA, p-PKA, CREB, and p-CREB increased following MA administration, but significantly decreased with CBD treatment. These results indicate that chronic MA administration leads to cardiotoxicity, but these effects can be attenuated by CBD pretreatment. Conclusions: This study was the first to examine the protective effects of CBD on cardiotoxicity elicited by chronic MA exposure in rats. Our research suggests that CBD attenuates the cardiac inflammatory response induced by MA through the PKA/CREB pathway, and CBD may have potential clinical application in the treatment of MA-induced cardiotoxicity.

14.
Environ Sci Ecotechnol ; 9: 100134, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36157858

RESUMEN

As the world's biggest carbon dioxide (CO2) emitter and the largest developing country, China faces daunting challenges to peak its emissions before 2030 and achieve carbon neutrality within 40 years. This study fully considered the carbon-neutrality goal and the temperature rise constraints required by the Paris Agreement, by developing six long-term development scenarios, and conducting a quantitative evaluation on the carbon emissions pathways, energy transformation, technology, policy and investment demand for each scenario. This study combined both bottom-up and top-down methodologies, including simulations and analyses of energy consumption of end-use and power sectors (bottom-up), as well as scenario analysis, investment demand and technology evaluation at the macro level (top-down). This study demonstrates that achieving carbon neutrality before 2060 translates to significant efforts and overwhelming challenges for China. To comply with the target, a high rate of an average annual reduction of CO2 emissions by 9.3% from 2030 to 2050 is a necessity, which requires a huge investment demand. For example, in the 1.5 °C scenario, an investment in energy infrastructure alone equivalent to 2.6% of that year's GDP will be necessary. The technological pathway towards carbon neutrality will rely highly on both conventional emission reduction technologies and breakthrough technologies. China needs to balance a long-term development strategy of lower greenhouse gas emissions that meets both the Paris Agreement and the long-term goals for domestic economic and social development, with a phased implementation for both its five-year and long-term plans.

15.
Front Pharmacol ; 13: 972828, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36147353

RESUMEN

In the past decade, methamphetamine (METH) abuse has sharply increased in the United States, East Asia, and Southeast Asia. METH abuse not only leads to serious drug dependence, but also produces irreversible neurotoxicity. Currently, there are no approved pharmacotherapies for the treatment of METH use disorders. Cannabidiol (CBD), a major non-psychoactive (and non-addictive) cannabinoid from the cannabis plant, shows neuroprotective, antioxidative, and anti-inflammatory properties under METH exposure. At present, however, the mechanisms underlying these properties remain unclear, which continues to hinder research on its therapeutic potential. In the current study, computational simulations showed that CBD and METH may directly bind to the dopamine receptor D1 (DRD1) via two overlapping binding sites. Moreover, CBD may compete with METH for the PHE-313 binding site. We also found that METH robustly induced apoptosis with activation of the caspase-8/caspase-3 cascade in-vitro and in-vivo, while CBD pretreatment prevented these changes. Furthermore, METH increased the expression of DRD1, phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) at serine 421 (Ser421), and level of intracellular Ca2+ in-vitro and in-vivo, but these effects were blocked by CBD pretreatment. The DRD1 antagonist SCH23390 significantly prevented METH-induced apoptosis, MeCP2 phosphorylation, and Ca2+ overload in-vitro. In contrast, the DRD1 agonist SKF81297 markedly increased apoptosis, MeCP2 phosphorylation, and Ca2+ overload, which were blocked by CBD pretreatment in-vitro. These results indicate that CBD prevents METH-induced neurotoxicity by modulating DRD1-mediated phosphorylation of MeCP2 and Ca2+ signaling. This study suggests that CBD pretreatment may resist the effects of METH on DRD1 by competitive binding.

16.
Colloids Surf B Biointerfaces ; 218: 112712, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35921692

RESUMEN

Chemotherapy is severely limited by continuously decreased therapeutic efficacy and uncontrolled side effects on normal tissue, which can be improved by constructing a nanoparticle-based drug delivery system (DDS). Nevertheless, no studies have reported on DDS-based on carbon-nanodots (CNDs), combining subcellular organelle-targeted imaging/drug delivery, high drug loading content, and glutathione (GSH)-sensitive drug release into one system. Herein, the as-fabricated CNDs can be covalently conjugated with a mitochondria-targeting ligand (triphenylphosphine, TPP), a smart GSH-responsive disulfide linker (S-S), and the anticancer drug (camptothecin, CPT) to initially prepare a theranostic nano-DDS (TPP-CNDs-S-CPT) with the drug loading efficiency of 64.6 wt%. Owing to excellent water dispersibility, superior fluorescence properties, satisfactory cell permeability, and favorable biocompatibility, TPP-CNDs-S-CPT was successfully used for intracellular mitochondrial-targeted imaging in vitro. High intracellular GSH concentrations in tumor cells caused the cleavage of S-S, resulting in concomitant activation and release of CPT, as well as significant fluorescence enhancement. In vivo, TPP-CNDs-S-CPT exhibited lower biological toxicity and even higher tumor-activatable performance than free CPT, as well as specific cancer therapy with few side effects. The mitochondria-targeted ability and the precise drug-release in tumor make TPP-CNDs-S-CPT a hopeful chemotherapy prodrug, providing significant theoretical basis and data support for in-depth understanding and exploration of chemotherapeutic DDS-based on CNDs.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Profármacos , Camptotecina , Carbono , Línea Celular Tumoral , Disulfuros , Sistemas de Liberación de Medicamentos/métodos , Glutatión , Humanos , Ligandos , Mitocondrias , Sistema de Administración de Fármacos con Nanopartículas , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Medicina de Precisión , Agua
17.
Obes Sci Pract ; 2022 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-35941911

RESUMEN

Objective: Obesity is an important risk factor for COVID-19. However, whether obesity affects SARS-CoV-2 antibody production is unclear. This study aimed to identify the influence of obesity on neutralizing antibody production of an inactivated SARS-CoV-2 vaccine to better guide vaccination strategies. Methods: This cross-sectional study recruited a total of 239 healthcare workers (age, 21-50 years) from Suining Central Hospital during 22-23 April 2021. An electronic questionnaire on basic characteristics was completed by all participants. A general physical exam and fasting blood sampling by venipuncture were performed. Peripheral leukocyte counts and the ratios of leukocyte subsets, hepatorenal function, and the neutralizing antibody titers against SARS-CoV-2 were measured. Results: Among 239 healthcare workers, the participants with underweight, normal weight, overweight, and obesity accounted for 10.88%, 64.44%, 23.01%, and 1.67%, respectively. The highest peripheral monocyte counts were observed in the group with obesity, whereas the lowest were observed in the group with normal weight. Similar results were obtained with respect to percentage of peripheral monocytes. Participants with obesity had higher peripheral eosinophil counts and percentages than the other three groups. The median neutralizing antibody titer was 12.70 AU/mL, with 85.36% (n = 204) of participants were sufficiently protected against SARS-CoV-2. The lowest neutralizing antibody titers were observed in the group with obesity, whereas the highest were observed in the group that was underweight. Additionally, high BMI was significantly associated with high peripheral monocyte counts [B (95% CI) = 0.008 (0.002, 0.013)] and low neutralizing antibody titers [B (95% CI) = -1.934 (-3.663, -0.206)]. Conclusions: Obesity could induce chronic inflammation, and associated with lower neutralizing antibody titers against SARS-CoV-2 after inactivated SARS-CoV-2 vaccination.

18.
J Hazard Mater ; 439: 129596, 2022 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-35863221

RESUMEN

Ratiometric fluorescence sensor has high selectivity and good sensitivity; however, its development is limited by intricate design, tedious synthesis, etc. Herein, a facile and effective ratiometric fluorescence sensing platform for fluoride ion (F-) detection was developed by simply combining nitrogen-doped carbon dots (N-CDs) and morin-Al3+ based on inner filter effect (IFE). The competitive binding of F- to Al3+ obviously decreased morin-Al3+ fluorescence and increased N-CDs fluorescence, attributing to the inhibition of IFE between N-CDs and morin-Al3+. The as-constructed ratiometric fluorescence sensing platform can be used for F- detection with a wide linear range (0.5-150 µM) and a low detection limit (55.8 nM). Interestingly, with the introduction of F- into the N-CDs/morin-Al3+ sensing platform, a distinguishable change in fluorescence color from green to blue enabled the N-CDs/morin-Al3+ system to be used as a smartphone-assisted visual sensing platform for F- detection with a detection limit of 2.09 µM. This platform was successfully applied for the onsite monitoring of F- in various water samples with satisfying results. These findings provide a novel guidance for the facile construction of a ratiometric optical dual-mode and smartphone-assisted sensing platform based on CDs, revealing the broad application prospect of CDs in environmental monitoring field.


Asunto(s)
Carbono , Puntos Cuánticos , Flavonas , Colorantes Fluorescentes , Fluoruros , Flúor , Límite de Detección , Nitrógeno , Teléfono Inteligente
20.
Bioinorg Chem Appl ; 2022: 3790097, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35859703

RESUMEN

Black phosphorus (BP) consists of phosphorus atoms, an essential element of bone and nucleic acid, which covalently bonds to three adjacent phosphorus atoms to form a puckered bilayer structure. With its anisotropy, band gap, biodegradability, and biocompatibility properties, BP is considered promising for cancer therapy. For example, BP under irradiation can convert near-infrared (NIR) light into heat and reactive oxygen species (ROS) to damage cancer cells, called photothermal therapy (PTT) and photodynamic therapy (PDT). Compared with PTT and PDT, the novel techniques of sonodynamic therapy (SDT) and photoacoustic therapy (PAT) exhibit amplified ROS generation and precise photoacoustic-shockwaves to enhance anticancer effect when BP receives ultrasound or NIR irradiation. Based on the prospective phototherapy, BP with irradiation can cause a "double-kill" to tumor cells, involving tumor-structure damage induced by heat, ROS, and shockwaves and a subsequent anticancer immune response induced by in situ vaccines construction in tumor site, which is referred to as photoimmunotherapy (PIT). In conclusion, BP shows promise in natural antitumor biological activity, biological imaging, drug delivery, PTT/PDT/SDT/PAT/PIT, nanovaccines, nanoadjuvants, and combination immunotherapy regimens.

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