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1.
Artículo en Inglés | MEDLINE | ID: mdl-39367704

RESUMEN

PURPOSE: To evaluate ocular refractive development, choroidal thickness (ChT) and changes in choroidal blood flow in form-deprived myopia (FDM) Guinea pigs treated with repeated low-level red-light (RLRL) therapy. METHODS: Twenty-eight 3-week-old male tricolour Guinea pigs were randomised into three groups: normal controls (NC, n = 10), form-deprived (FD, n = 10) and red light treated with form-deprivation (RLFD, n = 8). Interocular refraction and axial length (AL) changes were monitored. Optical coherence tomography angiography (OCTA) measured choroidal thickness, vessel area density, vessel skeleton density and blood flow signal intensity (flux) in the choriocapillaris and medium-large vessel layers. The experimental intervention lasted 3 weeks. RESULTS: At week 3, the FD group had higher myopia and longer axial length than the NC group (all p < 0.001). The RLFD group had higher hyperopia and shorter axial length than the FD group (all p < 0.001). At week 1, the NC group had a thicker choroidal thickness than the FD group (p < 0.05). At weeks 2 and 3, the RLFD group had a thicker choroidal thickness than the FD group (p = 0.002, p < 0.001, respectively). Additionally, the NC group had higher vessel area density, vessel skeleton density and flux in the choriocapillaris layer than the FD group at the three follow-up time points (all p < 0.05). At week 3, the vessel skeleton density and flux were higher in the RLFD group than in the FD group (all p < 0.05). Correlation analysis results showed that weekly changes in refraction and choroidal thickness were negatively correlated with changes in axial length (all p < 0.05). Choroidal thickness changes were positively correlated with alterations in the vessel area density, vessel skeleton density and flux in the choriocapillaris layer, as well as vessel skeleton density and flux changes in the medium-large vessel layers (all p < 0.05). CONCLUSIONS: Repeated low-level red-light (RLRL) therapy retards FDM progression in Guinea pigs, potentially through increased choroidal blood flow in the choriocapillaris layer.

2.
Environ Sci Technol ; 58(41): 18222-18233, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39352010

RESUMEN

Soil contamination by multiple metals is a significant concern due to the interlinked mobilization processes. The challenges in comprehending this issue arise from the poorly characterized interaction among different metals and the complexities introduced by spatial and temporal heterogeneity in soil systems. We delved into these complexities by incubating size-fractionated paddy soils under both anaerobic and aerobic conditions, utilizing a combination of techniques for aqueous and colloidal analysis. The contaminated paddy soil predominantly consisted of particles measuring <53, 250-53, and 2000-250 µm, with the <53 µm fractions exhibiting the highest concentrations of multiple metals. Interestingly, despite their higher overall content, the <53 µm fractions released less dissolved metal. Furthermore, glucose enhanced the release of arsenic while simultaneously promoting the sequestration of other metals, such as Pb, Zn, and Cu. Utilizing asymmetric flow field-flow fractionation, we unveiled the presence of both fine (0.3-130 kDa) and large (130-450 nm) colloidal pools, each carrying various metals with different affinities for iron minerals and organic matter. Our results highlighted the pivotal role of the <53 µm fraction as a significant reservoir for multiple metal contaminants in paddy soils, in which the colloidal metals were mainly associated with organic matter. These findings illuminated the size-resolved dynamics of soil metal cycling and provided insights for developing remediation strategies for metal-contaminated soil ecosystems.


Asunto(s)
Coloides , Oxidación-Reducción , Contaminantes del Suelo , Suelo , Suelo/química , Coloides/química , Metales , Oryza/química
3.
FEBS J ; 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279038

RESUMEN

Disrupted cholesterol homeostasis plays a critical role in the development of multiple diseases, such as cardiovascular disease and cancer. However, the role of cholesterol in inflammatory bowel disease (IBD) remains unclear. In the present study, we investigated whether and how high levels of cholesterol in the diet affect experimental colitis in mice. A normal diet supplemented with 1.25% cholesterol (high cholesterol diet) caused more severe colitis and aggravated the disruption of intestinal tight junction structure, accompanied by higher colonic tissue total cholesterol (TC) levels in a dextran sulfate sodium (DSS)-induced experimental colitis mouse model. Cholesterol aggravated DSS-induced intestinal epithelial barrier impairment and nuclear sterol regulatory element-binding protein 2 (nSREBP2) inhibition both in vivo and in vitro. In addition, nSREBP2 overexpression ameliorated cholesterol-induced intestinal epithelial barrier disruption in Caco2 cells. Interestingly, inhibition of SREBP2 disrupted intestinal epithelial barrier in the absence of cholesterol. Furthermore, SREBP2 regulated the protein expression of tight junction proteins (occludin/Zo-1) via modulating caveolin-1-mediated endocytosis and lysosomal degradation. Analysis of UK Biobank data indicated that, in fully adjusted models, higher serum TC concentrations were an independent protective factor for IBD incidence. The sterol regulatory element-binding factor 2 (SREBF2) gene rs2228313 (G/C) genetic variant was associated with the incidence of IBD and the CC genotype of SREBF2 rs2228313 was associated with higher serum TC levels and decreased the risk of IBD. In summary, a high cholesterol diet aggravates DSS-induced colitis in mice by down-regulating nSREBP2 expression, thereby promoting the endocytic degradation of tight junction proteins. In humans, SREBF2 gene single nucleotide polymorphism rs2228313 and serum TC levels are associated with IBD incidence.

4.
World J Surg Oncol ; 22(1): 241, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39245733

RESUMEN

BACKGROUND: This study aimed to construct a novel nomogram based on the number of positive lymph nodes to predict the overall survival of patients with pancreatic head cancer after radical surgery. MATERIALS AND METHODS: 2271 and 973 patients in the SEER Database were included in the development set and validation set, respectively. The primary clinical endpoint was OS (overall survival). Univariate and multivariate Cox regression analyses were used to screen independent risk factors of OS, and then independent risk factors were used to construct a novel nomogram. The C-index, calibration curves, and decision analysis curves were used to evaluate the predictive power of the nomogram in the development and validation sets. RESULTS: After multivariate Cox regression analysis, the independent risk factors for OS included age, tumor extent, chemotherapy, tumor size, LN (lymph nodes) examined, and LN positive. A nomogram was constructed by using independent risk factors for OS. The C-index of the nomogram for OS was 0.652 [(95% confidence interval (CI): 0.639-0.666)] and 0.661 (95%CI: 0.641-0.680) in the development and validation sets, respectively. The calibration curves and decision analysis curves proved that the nomogram had good predictive ability. CONCLUSIONS: The nomogram based on the number of positive LN can effectively predict the overall survival of patients with pancreatic head cancer after surgery.


Asunto(s)
Ganglios Linfáticos , Nomogramas , Neoplasias Pancreáticas , Programa de VERF , Humanos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Masculino , Femenino , Persona de Mediana Edad , Tasa de Supervivencia , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Anciano , Estudios de Seguimiento , Pronóstico , Factores de Riesgo , Metástasis Linfática , Pancreatectomía/mortalidad , Estudios Retrospectivos , Adulto
5.
Front Med (Lausanne) ; 11: 1440225, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323466

RESUMEN

Background: Listeria monocytogenes is a Gram-positive bacterium transmitted to humans through contaminated food, water, and animal faeces, posing a public health risk. Listeria monocytogenes is difficult to isolate and is not sensitive to first-line treatment with broad-spectrum cephalosporins for bacterial meningitis. Listeria meningitis is rare but can progress rapidly and may be accompanied by serious complications (hydrocephalus, ventricular inflammation, cerebral palsy, and brain abscess) and a high mortality rate. Case presentation: It is a retrospective analysis of the clinical characteristics and treatment of a rare case of Listeria monocytogenes infection. Using laboratory indicators such as white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT), three detection methods (cerebrospinal fluid/blood culture), Targeted gene sequencing technology (tNGS), and Metagenomic next-generation sequencing technology (mNGS) combined with clinical manifestations of patients, analyze the use plan and prognosis of antibiotics in patients. The patient in this case initially had neurological symptoms such as fever, headache, unclear consciousness, and vomiting; laboratory indicators include elevated WBC, CRP, and PCT. Listeria monocytogenes was cultured in both the patient's cerebrospinal fluid and blood samples. After treatment with penicillin and meropenem, the patient recovered and was discharged without any sequelae. Conclusion: Due to the rarity of Listeria monocytogenes, there may be deficiencies and difficulties in clinical differential diagnosis, making it difficult to achieve targeted antibiotic treatment. Therefore, accurate identification of Listeria monocytogenes and relevant laboratory inflammation indicator testing, combined with traditional culture methods and NGS testing, through empirical coverage of Listeria monocytogenes, targeted antibiotic treatment ultimately impacts clinical outcomes significantly.

6.
Chem Commun (Camb) ; 60(81): 11434-11449, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39258509

RESUMEN

Sulfonimide salts are considered as promising electrolyte materials in the construction of high-performant rechargeable lithium-ion batteries (LIBs) and lithium metal batteries (LMBs), owing to their delocalized negative charges, superior structural flexibility, and decent thermal/chemical stability. In this work, a historical overview of the development of sulfonimide anions in the field of electrolyte materials is presented, and the unique features of sulfonimide anions are discussed, in comparison with some popular anions [e.g., hexafluorophosphate anion (PF6-)] being employed for batteries. The key advances in the design of sulfonimide salts as electrolyte materials are scrutinized, encompassing their use in nonaqueous liquid electrolytes, ionic liquid electrolytes, and solid polymer electrolytes. Based on the existing reports and our experiences in this domain, possible research directions related to further improvement of sulfonimide-based electrolytes are highlighted. Besides demonstrating the status quo and research progress, this work also expands the structural design toolkit of sulfonimide-based electrolytes, which may accelerate the development and realization of sulfonimide anion-based electrolytes in practical LIBs/LMBs and simultaneously give new impetus to other kinds of rechargeable battery technologies (e.g., sodium and potassium batteries).

7.
Reproduction ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39312648

RESUMEN

Hypoxia is closely associated with physiological and pathological conditions in the human body, and the myometrium is affected by hypoxic stress during pregnancy and delivery. Autophagy is a catabolic pathway involved in the regulation of apoptosis, proliferation and migration of a variety of cells, which can be activated under hypoxia. However, the mechanism and function of autophagy in uterine smooth muscle cells remained unclear. The aim of this study was to investigate the changes of autophagy in pregnant uterine smooth muscle cells (pUSMCs) under hypoxia and the effect of autophagy on myometrial cells proliferation during pregnancy. In this study, primary uterine smooth muscle cells were isolated from mice in late pregnancy and cultured under normoxic and hypoxic conditions respectively. Western blotting and immunofluorescence were used to detect the expression levels of autophagy-related proteins LC3B, P62, mTOR and p-mTOR under different culture conditions. Cell proliferation was assessed by CCK-8 assay. In addition, 3-Methyladenine (3-MA) was used to inhibit autophagy in hypoxia-treated pUSMCs and MHY1485 was used to activate mTOR. Studies have confirmed that under hypoxic conditions, autophagy is enhanced and cell proliferative viability is reduced in pUSMCs. Autophagy inhibitor 3-MA restored cell proliferation inhibited by hypoxia. Furthermore, hypoxia in pUSMCs led to a downregulation of p-mTOR/mTOR levels. The mTOR activator MHY1485 inhibited autophagy by preventing the binding of autophagosomes to lysosomes and reversed the hypoxia-induced inhibition of cell proliferation. Collectively, our results indicate that hypoxia upregulates autophagy through the mTOR pathway in pUSMCs, thereby inhibiting cell proliferation during pregnancy.

8.
J Integr Neurosci ; 23(8): 156, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39207077

RESUMEN

PURPOSE: To investigate the relationship of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) parameters with dysfunction in acute focal cerebral ischemia (ACI) rabbits. METHODS: The model of ACI in the middle cerebral artery was made using 30 adult male New Zealand rabbits. The dysfunction severities of the ACI rabbits were assessed using Purdy's score. A paired-sample rank sum test was adopted to compare the abnormal signal zone (ASZ) volumes from T2 weighted imaging (T2WI), dynamic susceptibility contrast-enhanced (DSC) imaging, and DWI with a relative cerebral blood flow (rCBF) map; correlations were analyzed between the volume of each ASZ and Purdy's score by Spearman's rank correlation coefficient. The degree of necrotic and apoptotic cells was evaluated in the ASZ from DWI and DSC PWI-DWI mismatch (PDM) zone. Correlations were analyzed between the index of cellular damage and Purdy's score, the volume of ASZs by Spearman's rank correlation coefficient. RESULTS: The ASZ volumes from DSC-PWI and the rCBF maps were larger than those from DWI (p < 0.001 and p < 0.001, respectively); those from the rCBF map (Z = 0.959, p < 0.001) and DSC-PWI (Z = 0.970, p < 0.001) were positively correlated with DWI; a positive correlation was found between Purdy's score and the ASZ volumes from DSC-PWI (Z = 0.889, p < 0.001), DWI (Z = 0.921, p < 0.001), and rCBF (Z = 0.891, p < 0.001). A significant difference was observed between the ASZ from DWI and the PDM zone in terms of the degree of necrotic (p < 0.001) and apoptotic cells (p < 0.001). The degree of cellular damage in the ASZ of DWI and PDM zone had no relationship with Purdy's score and the volumes of ASZs. CONCLUSION: The ASZ volumes from DSC-PWI, rCBF, and particularly DWI reflected the level of dysfunction in rabbits with ACI.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Modelos Animales de Enfermedad , Animales , Conejos , Masculino , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/patología , Circulación Cerebrovascular/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen de Perfusión/métodos
9.
J Affect Disord ; 366: 370-378, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39197553

RESUMEN

BACKGROUND: Mitochondria is essential for cellular energy production, oxidative stress, and apoptosis. Mitochondrial DNA (mtDNA) encodes essential proteins for mitochondrial function. Although several studies have explored the association between changes in mtDNA copy number (mtDNA-CN) and risk of mental disorders, the results remain debated. This study used a bidirectional two-sample Mendelian randomization (MR) analysis to examine the genetic causality between mtDNA-CN and mental disorders. METHODS: Genome-wide association study (GWAS) data for mtDNA-CN were sourced from UK biobank, involving 383,476 European cases. GWAS data for seven mental disorders-attention deficit/hyperactivity disorder, autism spectrum disorder (ASD), schizophrenia, bipolar disorder, major depressive disorder, anxiety, and obsessive-compulsive disorder-were primarily obtained from the Psychiatric Genomics Consortium. Causal associations were assessed using inverse variance weighting, with sensitivity analyses via the weighted median and MR-Egger methods. Reverse MR considered the seven mental disorders as exposures. All analyses were replicated with additional mtDNA-CN GWAS data from 465,809 individuals in the Heart and Ageing Research in Genomic Epidemiology consortium and the UK Biobank. RESULTS: Forward MR observed a 27 % decrease in the risk of ASD per standard deviation increase in genetically determined blood mtDNA-CN (OR = 0.73, 95%CI: 0.58-0.92, p = 0.002), with no causal effects on other disorders. Additionally, reverse MR did not indicate a causal association between any of the mental disorders and mtDNA-CN. Validation analyses corroborated these findings, indicating their robustness. CONCLUSIONS: Our study supports the potential causal association between mtDNA-CN and the risk of ASD, suggesting that mtDNA-CN could serve as a promising biomarker for early screening of ASD.


Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos Mentales , Humanos , ADN Mitocondrial/genética , ADN Mitocondrial/sangre , Trastornos Mentales/genética , Trastornos Mentales/epidemiología , Trastornos Mentales/sangre , Femenino , Predisposición Genética a la Enfermedad , Masculino
10.
Water Res ; 263: 122198, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39098158

RESUMEN

The cycling processes of elemental manganese (Mn), including the redox reactions of dissolved Mn(III) (dMn(III)), directly and indirectly influences the biogeochemical processes of many elements. Though increasing evidence indicates the widespread presence of dMn(III) mediates the fate of many elements, its role may be currently underestimated. There is both a lack of clear understanding of the historical research framework of dMn(III) and a systematic overview of its geochemical properties and detection methods. Therefore, the primary aim of this review is to outline the understanding of dMn(III) in multiple fields, including soil science, analytical chemistry, biochemistry, geochemistry, and water treatment, and summarize the formation pathways, species forms, and detection methods of dMn(III) in aquatic systems. This review considers how the characteristics of dMn(III), the intermediate formed in the single-electron reaction processes of Mn(II) oxidation and Mn(IV) reduction, determines its participation in environmental geochemical processes. Its widespread presence in diverse water systems and active redox properties coupling with various elements confirm its significant role in natural elemental geochemistry cycle and artificial water treatment processes. Therefore, further investigation into the role of dissolved Mn(III) in aquatic systems is warranted to unravel unexplored coupled elemental redox reaction processes mediated by dissolved Mn(III), filling in the gaps in our understanding of manganese environmental geochemistry, and providing a theoretical basis for recognizing the role of dMn(III) role in water treatment technologies.


Asunto(s)
Manganeso , Manganeso/química , Oxidación-Reducción , Contaminantes Químicos del Agua/química , Ambiente
11.
J Integr Plant Biol ; 66(10): 2083-2086, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39109980

RESUMEN

The programmable nuclease TnpB is significantly smaller than Cas9, can edit genes in medicinal plants, including Artemisia annua, Salvia miltiorrhiza, Scutellaria baicalensis, Isatis indigotica, and Codonopsis pilosula, and has potential uses in molecular breeding to enhance crop yield and quality.


Asunto(s)
Arabidopsis , Elementos Transponibles de ADN , Plantas Medicinales , Plantas Medicinales/genética , Elementos Transponibles de ADN/genética , Arabidopsis/genética , Mutagénesis/genética
12.
Res Diagn Interv Imaging ; 9: 100038, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39076579

RESUMEN

Objective: The objective of this study was to evaluate the clinical feasibility of deep learning reconstruction-accelerated thin-slice single-breath-hold half-Fourier single-shot turbo spin echo imaging (HASTEDL) for detecting pancreatic lesions, in comparison with two conventional T2-weighted imaging sequences: compressed-sensing HASTE (HASTECS) and BLADE. Methods: From March 2022 to January 2023, a total of 63 patients with suspected pancreatic-related disease underwent the HASTEDL, HASTECS, and BLADE sequences were enrolled in this retrospectively study. The acquisition time, the pancreatic lesion conspicuity (LCP), respiratory motion artifact (RMA), main pancreatic duct conspicuity (MPDC), overall image quality (OIQ), signal-to-noise ratio (SNR), and contrast-noise-ratio (CNR) of the pancreatic lesions were compared among the three sequences by two readers. Results: The acquisition time of both HASTEDL and HASTECS was 16 s, which was significantly shorter than that of 102 s for BLADE. In terms of qualitative parameters, Reader 1 and Reader 2 assigned significantly higher scores to the LCP, RMA, MPDC, and OIQ for HASTEDL compared to HASTECS and BLADE sequences; As for the quantitative parameters, the SNR values of the pancreatic head, body, tail, and lesions, the CNR of the pancreatic lesion measured by the two readers were also significantly higher for HASTEDL than for HASTECS and BLADE sequences. Conclusions: Compared to conventional T2WI sequences (HASTECS and BLADE), deep-learning reconstructed HASTE enables thin slice and single-breath-hold acquisition with clinical acceptable image quality for detection of pancreatic lesions.

13.
Angew Chem Int Ed Engl ; : e202410017, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39072969

RESUMEN

As a fundamental industrial catalytic process, the semihydrogenation of alkynes presents a challenge in striking a balance between activity and selectivity due to the issue of over-hydrogenation. Herein, we develop an efficient catalytic system based on single-atom Pd catalysts supported on boron-containing amorphous zeolites (Pd/AZ-B), achieving the tradeoff breaking between the activity and selectivity for the selective hydrogenation of alkynes. Advanced characterizations and theoretical density functional theory calculations confirm that the incorporated B atoms in the Pd/AZ-B can not only alter the geometric and electronic properties of Pd atoms by controlling the electron migration from Pd but also mitigate the interaction between alkene and the catalyst supports. This boosts the exceptional catalytic efficacy in the semihydrogenation of phenylacetylene to styrene under mild conditions (298 K, 2 bar H2), achieving a recorded turnover frequency (TOF) value of 24198 h-1 and demonstrating 95 % selectivity to styrene at full conversion of phenylacetylene. By comparison, the heteroatom-free amorphous zeolite-anchored Pd nanoparticles and the commercial Lindlar catalyst have styrene selectivities of 73 % and 15 %, respectively, under identical reaction conditions. This work establishes a solid foundation for developing highly active and selective hydrogenation catalysts by controllably optimizing their electronic and steric properties.

14.
Environ Sci Technol ; 58(28): 12430-12440, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38968084

RESUMEN

Soil organic carbon (SOC) is pivotal for both agricultural activities and climate change mitigation, and biochar stands as a promising tool for bolstering SOC and curtailing soil carbon dioxide (CO2) emissions. However, the involvement of biochar in SOC dynamics and the underlying interactions among biochar, soil microbes, iron minerals, and fresh organic matter (FOM, such as plant debris) remain largely unknown, especially in agricultural soils after long-term biochar amendment. We therefore introduced FOM to soils with and without a decade-long history of biochar amendment, performed soil microcosm incubations, and evaluated carbon and iron dynamics as well as microbial properties. Biochar amendment resulted in 2-fold SOC accrual over a decade and attenuated FOM-induced CO2 emissions by approximately 11% during a 56-day incubation through diverse pathways. Notably, biochar facilitated microbially driven iron reduction and subsequent Fenton-like reactions, potentially having enhanced microbial extracellular electron transfer and the carbon use efficiency in the long run. Throughout iron cycling processes, physical protection by minerals could contribute to both microbial carbon accumulation and plant debris preservation, alongside direct adsorption and occlusion of SOC by biochar particles. Furthermore, soil slurry experiments, with sterilization and ferrous iron stimulation controls, confirmed the role of microbes in hydroxyl radical generation and biotic carbon sequestration in biochar-amended soils. Overall, our study sheds light on the intricate biotic and abiotic mechanisms governing carbon dynamics in long-term biochar-amended upland soils.


Asunto(s)
Carbono , Hierro , Microbiología del Suelo , Suelo , Suelo/química , Hierro/química , Hierro/metabolismo , Carbón Orgánico/química , Dióxido de Carbono/metabolismo
15.
Emerg Microbes Infect ; 13(1): 2373307, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38953857

RESUMEN

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.


Asunto(s)
Anticuerpos Biespecíficos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Epítopos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Anticuerpos Biespecíficos/inmunología , Anticuerpos Biespecíficos/química , Anticuerpos Biespecíficos/farmacología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/inmunología , Humanos , Anticuerpos Antivirales/inmunología , Epítopos/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , COVID-19/inmunología , COVID-19/virología , COVID-19/prevención & control , Pruebas de Neutralización
16.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39000499

RESUMEN

General anesthetics may accelerate the neuropathological changes related to Alzheimer's disease (AD), of which amyloid beta (Aß)-induced toxicity is one of the main causes. However, the interaction of general anesthetics with different Aß-isoforms remains unclear. In this study, we investigated the effects of sevoflurane (0.4 and 1.2 maximal alveolar concentration (MAC)) on four Aß species-induced changes on dendritic spine density (DSD) in hippocampal brain slices of Thy1-eGFP mice and multiple epidermal growth factor-like domains 10 (MEGF10)-related astrocyte-mediated synaptic engulfment in hippocampal brain slices of C57BL/6 mice. We found that both sevoflurane and Aß downregulated CA1-dendritic spines. Moreover, compared with either sevoflurane or Aß alone, pre-treatment with Aß isoforms followed by sevoflurane application in general further enhanced spine loss. This enhancement was related to MEGF10-related astrocyte-dependent synaptic engulfment, only in AßpE3 + 1.2 MAC sevoflurane and 3NTyrAß + 1.2 MAC sevoflurane condition. In addition, removal of sevoflurane alleviated spine loss in Aß + sevoflurane. In summary, these results suggest that both synapses and astrocytes are sensitive targets for sevoflurane; in the presence of 3NTyrAß, 1.2 MAC sevoflurane alleviated astrocyte-mediated synaptic engulfment and exerted a lasting effect on dendritic spine remodeling.


Asunto(s)
Péptidos beta-Amiloides , Astrocitos , Región CA1 Hipocampal , Espinas Dendríticas , Ratones Endogámicos C57BL , Sevoflurano , Sinapsis , Sevoflurano/farmacología , Animales , Espinas Dendríticas/metabolismo , Espinas Dendríticas/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Ratones , Región CA1 Hipocampal/metabolismo , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/citología , Masculino , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Anestésicos por Inhalación/farmacología
17.
Chronobiol Int ; 41(7): 1058-1067, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38953516

RESUMEN

Shift work is a recognized work pattern for nurses worldwide. The disruption of shift workers' biological clocks usually leads to sleep disorders and affects their awareness at work. Eveningness and occupational stress might be effective in causing burnout syndrome. Therefore, this study aimed to evaluate the chronotype, job burnout and perceived stress among Chinese tertiary hospital nurses, and understand the predictors of circadian rhythm in this group. Between July and September 2020, 23 hospitals were randomly selected from 113 tertiary hospitals in Hunan Province. Twenty-five percent of the nurses working in each hospital were targeted for selection. 28.1% and 17.6% of nurses reported eveningness type and morningness type, respectively. The scores for emotional exhaustion, depersonalization, and perceived stress of eveningness nurses were higher than those of morningness counterparts. Eveningness nurses also reported a lower sense of personal accomplishment. Risk factors of eveningness included being under 30 years old, never exercising, having the stressors of late-night shifts and career development, higher levels of emotional exhaustion, sleep latency, sleep duration, and hypnotic use. Shifts may be unavoidable for nurses, nevertheless, understanding the predictors and related factors of chronotype for nurses is necessary for nursing educators and managers to develop a reasonable shift system and appropriate measures to assist nurses in adjusting their work.


Asunto(s)
Agotamiento Profesional , Cronotipo , Enfermeras y Enfermeros , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , China/epidemiología , Estudios Transversales , Pueblos del Este de Asia , Personal de Enfermería en Hospital/psicología , Estrés Laboral , Factores de Riesgo , Horario de Trabajo por Turnos , Sueño/fisiología , Encuestas y Cuestionarios , Centros de Atención Terciaria , Tolerancia al Trabajo Programado
18.
Adv Mater ; 36(33): e2310245, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38839065

RESUMEN

Non-aqueous electrolytes, generally consisting of metal salts and solvating media, are indispensable elements for building rechargeable batteries. As the major sources of ionic charges, the intrinsic characters of salt anions are of particular importance in determining the fundamental properties of bulk electrolyte, as well as the features of the resulting electrode-electrolyte interphases/interfaces. To cope with the increasing demand for better rechargeable batteries requested by emerging application domains, the structural design and modifications of salt anions are highly desired. Here, salt anions for lithium and other monovalent (e.g., sodium and potassium) and multivalent (e.g., magnesium, calcium, zinc, and aluminum) rechargeable batteries are outlined. Fundamental considerations on the design of salt anions are provided, particularly involving specific requirements imposed by different cell chemistries. Historical evolution and possible synthetic methodologies for metal salts with representative salt anions are reviewed. Recent advances in tailoring the anionic structures for rechargeable batteries are scrutinized, and due attention is paid to the paradigm shift from liquid to solid electrolytes, from intercalation to conversion/alloying-type electrodes, from lithium to other kinds of rechargeable batteries. The remaining challenges and key research directions in the development of robust salt anions are also discussed.

19.
Sensors (Basel) ; 24(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38931789

RESUMEN

Joint source-channel coding (JSCC) based on deep learning has shown significant advancements in image transmission tasks. However, previous channel-adaptive JSCC methods often rely on the signal-to-noise ratio (SNR) of the current channel for encoding, which overlooks the neural network's self-adaptive capability across varying SNRs. This paper investigates the self-adaptive capability of deep learning-based JSCC models to dynamically changing channels and introduces a novel method named Channel-Blind JSCC (CBJSCC). CBJSCC leverages the intrinsic learning capability of neural networks to self-adapt to dynamic channels and diverse SNRs without relying on external SNR information. This approach is advantageous, as it is not affected by channel estimation errors and can be applied to one-to-many wireless communication scenarios. To enhance the performance of JSCC tasks, the CBJSCC model employs a specially designed encoder-decoder. Experimental results show that CBJSCC outperforms existing channel-adaptive JSCC methods that depend on SNR estimation and feedback, both in additive white Gaussian noise environments and under slow Rayleigh fading channel conditions. Through a comprehensive analysis of the model's performance, we further validate the robustness and adaptability of this strategy across different application scenarios, with the experimental results providing strong evidence to support this claim.

20.
Vaccines (Basel) ; 12(6)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38932395

RESUMEN

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

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