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1.
J Colloid Interface Sci ; 675: 670-682, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38996697

RESUMEN

Lignin hydrogels have garnered significant attention due to their distinctive three-dimensional structures and potent swelling ability. In this work, a novel magnetic nanocomposite lignin hydrogel (MNLH) was fabricated through organic synthesis and solution immersion reduction. The obtained MNLH was used to activate persulfate(PDS) for pesticide degradation. Scanning electron microscopy (SEM), X-ray diffractometry (XRD), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the structure and morphology of MNLH. The influence of factors such as the lignin hydrogel to nano-zero-valent iron (nZVI) and copper oxide (CuO) mass ratio, MNLH dosage, initial pH on the MNLH/PDS/imidacloprid (IMI) system. Remarkably, the MNLH/PDS/IMI system has a removal rate of up to 100%. Quenching and electron paramagnetic resonance (EPR) studies disclosed that the MNLH/PDS system degraded IMI through a combination of free radical and non-free radical pathways, with the latter being dominant. More importantly, in this study, the toxicity and hydrolysis sites of IMI were analyzed using ECOSAR and Gaussian09, respectively, confirming the feasibility of activating persulfate with MNLH. These findings underscore the potential of MNLH as a function material suitable for facilitating the persulfate-activated degradation of organic pollutants.

2.
J Mater Chem B ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38978513

RESUMEN

Extracellular clustering of amyloid-ß (Aß) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aß1-42, Iowa mutation Aß, Dutch mutation Aß fibrils and oligomers exhibiting enhanced emission with high affinity. Importantly, F-SLCOOH can readily pass through the blood-brain barrier and shows highly selective binding toward the extracellular Aß aggregates in real-time in live animal imaging of a 5XFAD mice model. In addition, a high concentration of F-SLCOOH in both brain and plasma of wildtype mice after intraperitoneal administration was found. The ex vivo confocal imaging of hippocampal brain slices indicated excellent colocalization of F-SLCOOH with Aß positive NU1, 4G8, 6E10 A11 antibodies and THS staining dye, affirming its excellent Aß specificity and targetability. The molecular docking studies have provided insight into the unique and specific binding of F-SLCOOH with various Aß species. Importantly, F-SLCOOH exhibits remarkable anti-fibrillation properties against toxic Aß aggregate formation of Aß1-42, Iowa mutation Aß, and Dutch mutation Aß. F-SLCOOH treatment also exerts high neuroprotective functions and promotes autophagy lysosomal biogenesis in neuronal AD cell models. In summary, the present results suggest that F-SLCOOH is a highly promising theranostic agent for diagnosis and therapeutics of AD.

3.
PLoS One ; 19(7): e0306699, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38985727

RESUMEN

In order to optimize the spectrum allocation strategy of existing wireless communication networks and improve information transmission efficiency and data transmission security, this study uses the independent correlation characteristics of chaotic time series to simulate the collection and control strategy of bees, and proposes an artificial bee colony algorithm based on uniform mapping and collaborative collection control. Furthermore, it proposes an artificial bee colony algorithm based on uniform mapping and collaborative collection and control. The method begins by establishing a composite system of uniformly distributed Chebyshev maps. In the neighborhood intervals where the nectar sources are firmly connected and relatively independent, the algorithm then conducts a chaotic traversal search. The research results demonstrated the great performance of the suggested algorithm in each test function as well as the positive effects of the optimization search. The network throughput rate was over 300 kbps, the quantity of security service eavesdropping was below 0.1, and the spectrum utilization rate of the algorithm-based allocation method could be enhanced to 0.8 at the most. Overall, the performance of the proposed algorithm outperformed the comparison algorithm, with high optimization accuracy and a significant amount of optimization. This is favorable for the efficient use of spectrum resources and the secure transmission of communication data, and it encourages the development of spectrum allocation technology in wireless communication networks.


Asunto(s)
Algoritmos , Redes de Comunicación de Computadores , Tecnología Inalámbrica , Abejas/fisiología , Animales , Seguridad Computacional
4.
Angew Chem Int Ed Engl ; : e202407929, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38837292

RESUMEN

Mechanically interlocked molecules (MIMs) are promising platforms for developing functionalized artificial molecular machines. The construction of chiral MIMs with appealing circularly polarized luminescence (CPL) properties has boosted their potential application in biomedicine and the optical industry. However, there is currently little knowledge about the CPL emission mechanism or the emission dynamics of these related MIMs. Herein, we demonstrate that time-resolved circularly polarized luminescence (TRCPL) spectroscopy combined with transient absorption (TA) spectroscopy offers a feasible approach to elucidate the origins of CPL emission in pyrene-functionalized topologically chiral [2]catenane as well as in a series of pyrene-functionalized chiral molecules. For the first time, direct evidence differentiating the chiroptical signals originating from either topological (local state emission) or Euclidean chirality (excimer state emission) in these pyrene-functionalized chiral molecules has been discovered. Our work not only establishes a novel and ideal approach to study CPL mechanism, but also provides a theoretical foundation for the rational design of novel chiral materials in the future.

5.
J Hazard Mater ; 472: 134514, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38718511

RESUMEN

The removal of crude oil from spent hydrodesulfurization catalysts constitutes the preliminary stage in the recovery process of valuable metals. However, the traditional roasting method for the removal exhibits massive limitations. In view of this, the present study used an ultrasound-assisted surfactant cleaning method to remove crude oil from spent hydrodesulfurization catalysts, which demonstrated effectiveness. Furthermore, the study investigated the mechanism governing the process with calculation and experiments, so as to provide a comprehensive understanding of the cleaning method's efficacy. The surfactant selection was predicated on the performance in the IFT test, with SDBS and TX-100 finally being chosen. Subsequent calculations and analysis were then conducted to elucidate their frontier molecular orbitals, electrostatic potential, and polarity. It has been found that both SDBS and TX-100 possess the smallest LUMO-HOMO energy gap (ΔE), registering at 4.91 eV and 4.80 eV, respectively, and presenting the highest interfacial reactivity. The hydrophilic structure in the surfactant regulates the wettability of the oil-water interface, and the long-chain alkanes have excellent non-polar properties that promote the dissolution of crude oil. The ultrasonic-assisted process further improves the interface properties and enhances the oil removal effect. Surprisingly, the crude oil residue was reduced to 0.25% under optimal conditions. The final phase entailed the techno-economic evaluation of the entire process, revealing that, in comparison to the roasting method, this process saves $0.38 per kilogram of spent HDS catalyst, with the advantages of operational simplicity and emission-free. Generally, this study shed new light on the realization of efficient oil removal, with the salience of green, sustainable, and economical.

6.
Environ Sci Technol ; 58(17): 7335-7345, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38626301

RESUMEN

Interfacial solar vapor generation (ISVG) is an emerging technology to alleviate the global freshwater crisis. However, high-cost, low freshwater collection rate, and salt-blockage issues significantly hinder the practical application of solar-driven desalination devices based on ISVG. Herein, with a low-cost copper plate (CP), nonwoven fabric (NWF), and insulating ethylene-vinyl acetate foam (EVA foam), a multistage device is elaborately fabricated for highly efficient simultaneous freshwater and salt collection. In the designed solar-driven device, a superhydrophobic copper plate (SH-CP) serves as the condensation layer, facilitating rapid mass and heat transfer through dropwise condensation. Moreover, the hydrophilic NWF is designed with rational hydrophobic zones and specific high-salinity solution outlets (Design-NWF) to act as the water evaporation layer and facilitate directional salt collection. As a result, the multistage evaporator with eight stages exhibits a high water collection rate of 2.25 kg m-2 h-1 under 1 sun irradiation. In addition, the desalination device based on the eight-stage evaporator obtains a water collection rate of 13.44 kg m-2 and a salt collection rate of 1.77 kg m-2 per day under natural irradiation. More importantly, it can maintain a steady production for 15 days without obvious performance decay. This bifunctional multistage device provides a feasible and efficient approach for simultaneous desalination and solute collection.


Asunto(s)
Agua Dulce , Luz Solar , Salinidad , Purificación del Agua
7.
Environ Sci Pollut Res Int ; 31(22): 31771-31786, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38658509

RESUMEN

Persulfate-based advanced oxidation processes (PS-AOPs) have been widely investigated by academia and industry due to their high efficiency and selectivity for the removal of trace organic pollutants from complex water substrates. PS-AOPs have been extensively studied for the degradation of pesticides, drugs, halogen compounds, dyes, and other pollutants. Utilizing bibliometric statistics, this review presents a comprehensive overview of persulfate-based advanced oxidation technology research over the past decade. The number of published articles about persulfate activation has steadily increased during this time, reflecting extensive international collaboration. Furthermore, this review introduces the most widely employed strategies for persulfate activation reported in the past 10 years, including carbon material activation, photocatalysis, transition metal activation, electrochemical activation, ultrasonic activation, thermal activation, and alkali activation. Next, the potential activation mechanisms and influencing factors, such as persulfate dosage during activation, are discussed. Finally, the application of PS-AOPs in wastewater treatment and in situ groundwater treatment is examined. This review summarizes the previously reported experiences of persulfate-based advanced oxidation technology and presents the current application status of PS-AOPs in organic pollution removal, with the aim of avoiding misunderstandings and providing a solid foundation for future research on the removal of organic pollutants.


Asunto(s)
Oxidación-Reducción , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Sulfatos/química
8.
J Chem Phys ; 160(12)2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38526107

RESUMEN

Proflavine (PF), an acridine DNA intercalating agent, has been widespread applied as an anti-microbial and topical antiseptic agent due to its ability to suppress DNA replication. On the other hand, various studies show that PF intercalation to DNA can increase photogenotoxicity and has potential chances to induce carcinomas of skin appendages. However, the effects of PF intercalation on the photophysical and photochemical properties of DNA have not been sufficiently explored. In this study, the excited state dynamics of the PF intercalated d(GC)9 • d(GC)9 and d(AT)9 • d(AT)9 DNA duplex are investigated in an aqueous buffer solution. Under 267 nm excitation, we observed ultrafast charge transfer (CT) between PF and d(GC)9 • d(GC)9 duplex, generating a CT state with an order of magnitude longer lifetime compared to that of the intrinsic excited state reported for the d(GC)9 • d(GC)9 duplex. In contrast, no excited state interaction was detected between PF and d(AT)9 • d(AT)9. Nevertheless, a localized triplet state with a lifetime over 5 µs was identified in the PF-d(AT)9 • d(AT)9 duplex.


Asunto(s)
Sustancias Intercalantes , Proflavina , Proflavina/química , Análisis Espectral , Sustancias Intercalantes/química , ADN/química
9.
PLoS Genet ; 20(3): e1011196, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38466721

RESUMEN

Hematophagous mosquitoes require vertebrate blood for their reproductive cycles, making them effective vectors for transmitting dangerous human diseases. Thus, high-intensity metabolism is needed to support reproductive events of female mosquitoes. However, the regulatory mechanism linking metabolism and reproduction in mosquitoes remains largely unclear. In this study, we found that the expression of estrogen-related receptor (ERR), a nuclear receptor, is activated by the direct binding of 20-hydroxyecdysone (20E) and ecdysone receptor (EcR) to the ecdysone response element (EcRE) in the ERR promoter region during the gonadotropic cycle of Aedes aegypti (named AaERR). RNA interference (RNAi) of AaERR in female mosquitoes led to delayed development of ovaries. mRNA abundance of genes encoding key enzymes involved in carbohydrate metabolism (CM)-glucose-6-phosphate isomerase (GPI) and pyruvate kinase (PYK)-was significantly decreased in AaERR knockdown mosquitoes, while the levels of metabolites, such as glycogen, glucose, and trehalose, were elevated. The expression of fatty acid synthase (FAS) was notably downregulated, and lipid accumulation was reduced in response to AaERR depletion. Dual luciferase reporter assays and electrophoretic mobility shift assays (EMSA) determined that AaERR directly activated the expression of metabolic genes, such as GPI, PYK, and FAS, by binding to the corresponding AaERR-responsive motif in the promoter region of these genes. Our results have revealed an important role of AaERR in the regulation of metabolism during mosquito reproduction and offer a novel target for mosquito control.


Asunto(s)
Aedes , Receptores de Esteroides , Animales , Femenino , Humanos , Aedes/genética , Aedes/metabolismo , Ecdisona/metabolismo , Mosquitos Vectores/genética , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Homeostasis/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo
10.
Front Microbiol ; 15: 1356903, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550873

RESUMEN

Introduction: Spent mushroom substrate (SMS) is a solid waste in agricultural production that contains abundant lignocellulosic fibers. The indiscriminate disposal of SMS will lead to significant resource waste and pollution of the surrounding environment.The isolation and screening of microorganisms with high cellulase degradation capacity is the key to improving SMS utilization. Methods: The cellulose-degrading microbial consortiums were constructed through antagonism and enzyme activity test. The effect of microbial consortiums on lignocellulose degradation was systematically evaluated by SMS liquid fermentation experiments. Results: In this study, four strains of cellulose-degrading bacteria were screened, and F16, F, and F7 were identified as B. amyloliquefaciens, PX1 identified as B. velezensis. At the same time, two groups of cellulose efficient degrading microbial consortiums (PX1 + F7 and F16 + F) were successfully constructed. When SMS was used as the sole carbon source, their carboxymethyl cellulase (CMCase) activities were 225.16 and 156.63 U/mL, respectively, and the filter paper enzyme (FPase) activities were 1.91 and 1.64 U/mL, respectively. PX1 + F7 had the highest degradation rate of hemicellulose and lignin, reaching 52.96% and 52.13%, respectively, and the degradation rate of F16 + F was as high as 56.30%. Field emission scanning electron microscopy (FESEM) analysis showed that the surface microstructure of SMS changed significantly after microbial consortiums treatment, and the change of absorption peak in Fourier transform infrared spectroscopy (FTIR) and the increase of crystallinity in X-ray diffraction (XRD) confirmed that the microbial consortiums had an actual degradation effect on SMS. The results showed that PX1 + F7 and F16 + F could effectively secrete cellulase and degrade cellulose, which had practical significance for the degradation of SMS. Discussion: In this study, the constructed PX1 + F7 and F16 + F strains can effectively secrete cellulase and degrade cellulose, which holds practical significance in the degradation of SMS. The results can provide technical support for treating high-cellulose solid waste and for the comprehensive utilization of biomass resources.

11.
Neurobiol Dis ; 194: 106471, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38461868

RESUMEN

Emerging evidence has implicated an important role of synapse-associated protein-97 (SAP97)-regulated GluA1-containing AMPARs membrane trafficking in cocaine restate and in contextual episodic memory of schizophrenia. Herein, we investigated the role of SAP97 in neuropathic pain following lumbar 5 spinal nerve transection (SNT) in rats. Our results showed that SNT led to upregulation of SAP97, enhanced the interaction between SAP97 and GluA1, and increased GluA1-containing AMPARs membrane trafficking in the dorsal horn. Microinjection of AAV-EGFP-SAP97 shRNA in lumbar 5 spinal dorsal horn inhibited SAP97 production, decreased SAP97-GluA1 interaction, reduced the membrane trafficking of GluA1-containing AMPARs, and partially attenuated neuropathic pain following SNT. Intrathecal injections of SAP97 siRNA or NASPM, an antagonist of GluA1-containing AMPARs, also partially reversed neuropathic pain on day 7, but not on day 14, after SNT. Spinal overexpression of SAP97 by AAV-EGFP-SAP97 enhanced SAP97-GluA1 interaction, increased the membrane insertion of GluA1-containing AMPARs, and induced abnormal pain in naïve rats. In addition, treatment with SAP97 siRNA or NASPM i.t. injection alleviated SNT-induced allodynia and hyperalgesia and exhibited a longer effect in female rats. Together, our results indicate that the SNT-induced upregulation of SAP97 via promoting GluA1-containing AMPARs membrane trafficking in the dorsal horn contributes to the pathogenesis of neuropathic pain. Targeting spinal SAP97 might be a promising therapeutic strategy to treatment of chronic pain.


Asunto(s)
Neuralgia , Receptores AMPA , Espermina , Animales , Femenino , Ratas , Hiperalgesia , Ratas Sprague-Dawley , Receptores AMPA/metabolismo , ARN Interferente Pequeño , Espermina/análogos & derivados , Asta Dorsal de la Médula Espinal/metabolismo , Nervios Espinales , Regulación hacia Arriba
12.
J Phys Chem Lett ; 15(10): 2765-2771, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38482678

RESUMEN

Gilvocarcin V (GV) is a natural antibiotic exhibiting excellent antitumor activities and remarkably low toxicity in near-ultraviolet or visible light-dependent treatment. Notwithstanding, the [2 + 2] cycloaddition reaction between GV and thymine has been proven to be the key for its function in photodynamic therapy, and crucial mechanistic details about such a reaction are poorly understood. In this study, the electronic relaxation pathways and photoaddition reaction are characterized by femto- to nanosecond time-resolved spectroscopy combined with quantum chemical calculation. Our results reveal that ultrafast intersystem crossing (<3 ps) leads to the population of a local triplet excited state in DNA-intercalated GV. Such a state can further induce the formation of a biradical state, which is identified as the important reactive precursor for photoaddition between GV and thymine. The overall photoaddition quantum efficiency is determined to be 11.57 ± 1.0%. These results are essential to the elucidation of the DNA photoaddition mechanism of C-aryl glycoside-based artificial photocytotoxic agents and could help further development of those medicines.


Asunto(s)
Cumarinas , Glicósidos , Timina , Timina/química , ADN/química , Antibacterianos
13.
Clin Transl Oncol ; 26(6): 1459-1466, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38329609

RESUMEN

OBJECTIVE: The objective of this study was to investigate the impact of Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline) on cardiac function in osteosarcoma patients and analyze the factors influencing this effect. METHODS: A retrospective study was conducted on 165 osteosarcoma patients admitted to our hospital from January 2020 to December 2022. Based on the chemotherapy regimen, the patients were divided into two groups: the control group (n = 62) treated with Cisplatin and cyclophosphamide, and the observation group (n = 103) treated with Doxorubicin, Epirubicin, and Liposomal Doxorubicin (Anthracycline). The general records of both groups were analyzed, and left ventricular ejection fraction (LVEF) was evaluated through echocardiography before and after chemotherapy. Blood cTnT and CK-MB levels were measured using immunoluminescence. The incidence of adverse reactions during chemotherapy was also analyzed. Univariate analysis was performed to identify patients with cardiotoxic events, and multiple logistic regression analysis was done to study the effects of Doxorubicin, Epirubicin, Liposomal Doxorubicin, and their dosages on cardiotoxicity in patients. RESULTS: The general records between the two groups showed no significant differences (P > 0.05). However, at the fourth cycle of chemotherapy, the observation group exhibited a lower LVEF (P < 0.05), and a higher percentage of LVEF decrease compared to the control group (P < 0.05). Moreover, the observation group had higher levels of blood cTnT and CK-MB (P < 0.05). The incidence of cardiotoxicity in the observation group was also higher (P < 0.05), but no significant differences were seen in other adverse reaction rates (P > 0.05). The occurrence of cardiotoxicity was found to be related to the choice and dosage of chemotherapy drugs (P < 0.05), but not significantly correlated with age, sex, and mediastinal irradiation in patients (P > 0.05). Furthermore, the use of Doxorubicin, Epirubicin, and Liposomal Doxorubicin in chemotherapy, as well as an increase in their dosages, was found to elevate the risk of cardiotoxicity in osteosarcoma patients (P < 0.05). However, age, sex, and mediastinal radiation were not significantly associated with cardiotoxicity in osteosarcoma patients (P > 0.05). CONCLUSION: We demonstrated that Doxorubicin, Epirubicin, Liposomal Doxorubicin (Anthracycline), and other drugs adversely affected cardiac function in osteosarcoma patients, increasing the risk of cardiac toxicity. Therefore, close monitoring of cardiac function during chemotherapy is crucial, and timely adjustments to the chemotherapy regimen are necessary. In addition, rational control of drug selection and dosage is essential to minimize the occurrence of cardiac toxicity.


Asunto(s)
Neoplasias Óseas , Cardiotoxicidad , Doxorrubicina , Epirrubicina , Osteosarcoma , Humanos , Osteosarcoma/tratamiento farmacológico , Epirrubicina/efectos adversos , Epirrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/análogos & derivados , Femenino , Masculino , Estudios Retrospectivos , Adulto , Adulto Joven , Neoplasias Óseas/tratamiento farmacológico , Cardiotoxicidad/etiología , Adolescente , Volumen Sistólico/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Función Ventricular Izquierda/efectos de los fármacos , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/uso terapéutico , Ecocardiografía , Troponina T/sangre , Forma MB de la Creatina-Quinasa/sangre , Ciclofosfamida/efectos adversos , Ciclofosfamida/administración & dosificación , Niño , Cisplatino/efectos adversos , Cisplatino/administración & dosificación , Polietilenglicoles
14.
Aging Clin Exp Res ; 36(1): 30, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38334839

RESUMEN

BACKGROUND: Widespread attention has been given to the detrimental effects of obesity on cognitive function. However, there is no evidence on the connection between low cognitive performance and the WWI (weight-adjusted waist index). This study looked into the connection between poor cognitive performance and the WWI in senior Americans. METHODS: A cross-sectional research study was carried out with information from the NHANES 2011-2014. With multivariate linear regression models, the pertinence between the WWI and low cognitive function in persons older than 60 years was examined. The nonlinear link was described using threshold effect analyses and fitted smoothed curves. Interaction tests and subgroup analysis were also conducted. RESULTS: The study had 2762 individuals in all, and subjects with higher WWI values were at greater risk for low cognitive function. In the completely adjusted model, the WWI was positively connected with low cognitive performance assessed by CERAD W-L (OR = 1.22, 95% CI 1.03-1.45, p = 0.0239), AFT (OR = 1.30, 95% CI 1.09-1.54, p = 0.0029), and DSST (OR = 1.59, 95% CI 1.30-1.94, p < 0.0001). The effect of each subgroup on the positive correlation between the WWI and low cognitive performance was not significant. The WWI and low cognitive performance as determined by CERAD W-L and AFT had a nonlinear connection (log-likelihood ratio < 0.05). CONCLUSION: Among older adults in the United States, the risk of low cognitive performance may be positively related to the WWI.


Asunto(s)
Cognición , Obesidad , Humanos , Anciano , Estudios Transversales , Encuestas Nutricionales , Modelos Lineales , Obesidad/epidemiología
15.
J Control Release ; 366: 479-493, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38184234

RESUMEN

mRNA-based vaccines and therapeutic agents hold great promise in prevention and treatment of human diseases, yet high percentage of systemic adverse effect in clinic remains a big safety concern. One major potential cause is a high level of leakage of the locally inoculated mRNA vaccine nanoparticles into circulation. We have screened and optimized a core-shell structured lipopolyplex (LPP) formulation for mRNA with a tissue-retention property. Upon intramuscular inoculation, the mRNA-encapsulated LPP nanoparticles were preferentially taken up by the phagocytic antigen-presentation cells, and potently promoted dendritic cell maturation. We applied the new formulation to prepare a prophylactic vaccine for SARS-CoV-2, and observed potent humoral and cellular immune responses from the vaccine in both murine models and non-human primates. More importantly, the vaccine demonstrated a benign safety profile in non-human primates, with limited side effects after repeated treatment with high dosages of LPP/mRNA. Taken together, the inoculation site-retained vaccine formulation serves as a promising vehicle for mRNA vaccines and therapeutic agents.


Asunto(s)
COVID-19 , Vacunas de ARNm , Humanos , Animales , Ratones , SARS-CoV-2/genética , Vacunas contra la COVID-19 , COVID-19/prevención & control , Presentación de Antígeno , ARN Mensajero , Primates , Anticuerpos Antivirales , Anticuerpos Neutralizantes
16.
J Am Chem Soc ; 146(3): 1839-1848, 2024 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-38194423

RESUMEN

Epigenetic modifications impart important functionality to nucleic acids during gene expression but may increase the risk of photoinduced gene mutations. Thus, it is crucial to understand how these modifications affect the photostability of duplex DNA. In this work, the ultrafast formation (<20 ps) of a delocalized triplet charge transfer (CT) state spreading over two stacked neighboring nucleobases after direct UV excitation is demonstrated in a DNA duplex, d(G5fC)9•d(G5fC)9, made of alternating guanine (G) and 5-formylcytosine (5fC) nucleobases. The triplet yield is estimated to be 8 ± 3%, and the lifetime of the triplet CT state is 256 ± 22 ns, indicating that epigenetic modifications dramatically alter the excited state dynamics of duplex DNA and may enhance triplet state-induced photochemistry.


Asunto(s)
ADN , Epigénesis Genética , ADN/química , ADN/efectos de la radiación , Rayos Ultravioleta
17.
Nat Commun ; 15(1): 106, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168045

RESUMEN

Aedes aegypti are vectors for several arboviruses infecting hundreds of millions of people annually. Controlling mosquito populations by regulating their reproduction is a potential strategy to minimize viral transmission in the absence of effective antiviral therapies or vaccines. Here, we demonstrate that leucine aminopeptidase1 (LAP1), detected by a SWATH-MS-based proteomic screen of female spermathecae, is a crucial determinant in mosquito population expansion. Mitochondrial defects and aberrant autophagy of sperm in LAP1 mutant males (LAP1-/-), prepared using CRISPR/Cas9 system, result in a reduction of reproduction in wild-type females that mated with them. The fitness of LAP1-/- males is strong enough to efficiently transmit genetic changes to mosquito populations through a low number of hatchable offspring. Thus, LAP1-/- males represent an opportunity to suppress mosquito populations and further studies should be undertaken to characterize LAP1's suitability for gene drive usage.


Asunto(s)
Aedes , Animales , Masculino , Humanos , Femenino , Leucina , Proteómica , Mosquitos Vectores , Semen
18.
Nat Commun ; 15(1): 405, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38195782

RESUMEN

Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO2. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO2. The formation of TiO2(e-) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.


Asunto(s)
Irradiación Craneana , Neuronas Dopaminérgicas , Animales , Ratones , Potenciales de Acción , Difusión
19.
Sci Rep ; 14(1): 2291, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38280964

RESUMEN

In recent years, deep neural networks have evolved rapidly in engineering technology, with models becoming larger and deeper. However, for most companies, developing large models is extremely costly and highly risky. Researchers usually focus on the performance of the model, neglecting its cost and accessibility. In fact, most regular business scenarios do not require high-level AI. A simple and inexpensive modeling method for fulfilling certain demands for practical applications of AI is needed. In this paper, a Fragmented neural network method is proposed. Inspired by the random forest algorithm, both the samples and features are randomly sampled on image data. Images are randomly split into smaller pieces. Weak neural networks are trained using these fragmented images, and many weak neural networks are then ensembled to build a strong neural network by voting. In this way, sufficient accuracy is achieved while reducing the complexity and data volume of each base learner, enabling mass production through parallel and distributed computing. By conducting experiments on the MNIST and CIFAR10 datasets, we build a model pool using FNN, CNN, DenseNet, and ResNet as the basic network structure. We find that the accuracy of the ensemble weak network is significantly higher than that of each base learner. Meanwhile, the accuracy of the ensemble network is highly dependent on the performance of each base learner. The accuracy of the ensemble network is comparable to or even exceeds that of the full model and has better robustness. Unlike other similar studies, we do not pursue SOTA models. Instead, we achieved results close to the full model with a smaller number of parameters and amount of data.

20.
Biol Pharm Bull ; 47(2): 486-498, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38199251

RESUMEN

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.


Asunto(s)
Chalconas , Melanoma , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Melanoma/metabolismo , Diferenciación Celular , Vía de Señalización Wnt , Serina-Treonina Quinasas TOR/metabolismo , Proliferación Celular , Movimiento Celular , Línea Celular Tumoral
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