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1.
ACS Nano ; 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39342510

RESUMEN

van der Waals-layered niobium diselenide (NbSe2) intercalated by d-electron transition metals is an ideal test bed for the exploration of their diversiform evolution of ground states. These intercalations are mostly viewed as ordered structures aligned with periodicities of their host materials that enable control of the electronic phases via gradually changing of intercalation ratios. Here, we present the structure and superconductivity in tungsten (W)-intercalated 2H-NbSe2 crystals, which reveals an order to disorder distribution of W atoms with increasing confined intercalating amounts, leading to an approximate V-shape suppression of superconductivity. Aided by density functional theory calculations, we demonstrate that the local magnetic moment around W intercalants induced by the charge redistribution gives rise to the quick superconductivity suppression in 2H-NbSe2 below a certain dilute amount (W% = 0.06). Simultaneously, W intercalants also induce structural aberration due to aggregation effects and inhibit the generation of an ordered structure in 2H-NbSe2, resulting in a recovery of its superconductivity. The alteration of structure and electronic phases in 2H-NbSe2 via intercalation of nonmagnetic transition metals in the van der Waals gap enables the exploration of combined magnetic quantum criticality, superconductivity, and other related electronic correlations.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39324336

RESUMEN

Hybrid organic-inorganic molecular ferroelectrics (HOIMFs) have garnered significant attention owing to their potential applications in optoelectronic and spintronic devices. However, HOIMFs with high Curie temperature (Tc), narrow bandgap (Eg), excellent stability, and high breakdown voltage are still very rare. Herein, we present a novel lead-halide molecular ferroelectric, (1,4-butanediammonium)PbI4 (1), synthesized hydrothermally. 1 exhibits a ferroelectric-to-paraelectric phase transition with a high Curie temperature of 485 K, a room temperature ferroelectric hysteresis loop with a robust saturation polarization of 3.9 µC/cm2 and strong coercivity of 33 kV/cm, and a typical semiconductor behavior with a direct bandgap of 2.28 eV. Switchable photovoltaic effect was observed in 1-based device with a fast response time of ∼2 ms and high breakdown electric field of 80 kV/cm. Dramatically enhanced photovoltaic performance has been achieved by manipulating the ferroelectric polarization, resulting in a maximum photovoltage of Voc ∼ 0.84 V and a photocurrent of Jsc ∼ 33.31 nA/cm2 under standard AM 1.5 G illumination. This study offers a bright avenue for advancing high-Tc lead-halide molecular ferroelectrics with promising potentials in photodetectors, data storage, and logical switching devices.

3.
Front Plant Sci ; 15: 1416886, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39323534

RESUMEN

This study establishes the first core collection (CC) for Taiwanese Phalaenopsis orchids to preserve genetic diversity and key traits essential for breeding and research, thereby enhancing breeding efficiency without the need for a large maintained parent population. We examined 207 commercial orchid cultivars from ten nurseries, characterized by two phenotypes and genotypic data from eight simple sequence repeat markers. Multiple imputation was applied to estimate missing phenotypes, minimizing potential uncertainties and ensuring the reliability of population structure analysis. Weighted k-means clustering identified seven distinct clusters, highlighting substantial genetic diversity. We proposed a two-step phenotype and genotype strategy and modified genetic distance algorithms to effectively preserve both phenotypic and genetic diversity while retaining key features. Consequently, 22 core accessions were selected, distributed across seven clusters, and representing the orchid germplasm collection. Our evaluation revealed significant diversity preservation, particularly in distinct characteristics and rare features, outperforming other methodologies. Pedigree background analysis further confirmed the representativeness of the CC in maintaining diverse genetic materials. We emphasized the importance of evaluating the CC by detailing the criteria and statistical analyses used to ensure the quality, representativeness, and effectiveness of the selected accessions. This study contributes to orchid breeding, conservation efforts, and sustainable agricultural practices by providing a valuable and comprehensive resource. In conclusion, our research establishes a groundbreaking CC, offering insights into the genetic landscape of Taiwanese Phalaenopsis orchids and highlighting potential advancements in breeding commercially desirable varieties.

4.
Scand J Caring Sci ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39329224

RESUMEN

BACKGROUND: The visibility of skin lesions significantly burdens people with psoriasis, leading to social hostility and numerous emotional and psychological problems. These issues adversely affect self-esteem, can result in chronic mental health challenges and cause numerous life problems. This study aimed to explore patients' long-term experiences with severe psoriasis. METHODS: A qualitative study was conducted with 20 patients with psoriasis (PASI ≥12) recruited from general and specialist dermatology practices in a regional teaching hospital in Taiwan. Interviews lasted 60-90 min and data were analysed using content analysis. FINDINGS: A core theme emerged: 'Embodied suffering-life worse than death'. This overarching concept comprised three interrelated themes: (i) Experiencing physical suffering, (ii) Experiencing psychological suffering and (iii) Experiencing the stigma of suffering. CONCLUSION: This study highlights the holistic nature of suffering among individuals with severe psoriasis. It emphasises the need for healthcare professionals to consider the entirety of a patient's circumstances when addressing their suffering.

5.
Med Acupunct ; 36(4): 173-177, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39309623

RESUMEN

Pediatric tuina is a traditional Chinese medicine (TCM) modality that is well-accepted and applied in China currently. As a traditional medicine, it is based on TCM theories and clinical experience. In the TCM area, the "self-healing" system of the human body includes two aspects: self-regulation and adaptation, through which pediatric tuina could rectify dysfunctional states and guide the transition back to homeostasis. Pediatric tuina manipulations sufficiently, specifically, and accurately simulate certain sensory receptors in the skin, which in turn activates the internal self-healing function of the human body. We summarized the main opinions on pediatric tuina mechanism in ancient literature into three minor perspectives and demonstrated them by combining them with modern medical knowledge. First, children at a young age are more responsive to stimulations on the skin surface; second, the sensory receptors and pediatric tuina acupoints on the skin surface have a similar distribution pattern; third, the specific manipulations of pediatric tuina provide multiple stimuli that are detected by a variety of surface sensory receptors for information collection. Each point could be tested via clinical trials with appropriate-designed comparisons.

6.
Aging Clin Exp Res ; 36(1): 189, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259235

RESUMEN

The prevalence of frailty is increasing, and it is associated with increased risk of diseases and adverse outcomes. Although substantial research has focused on post-stroke frailty, understanding of pre-stroke frailty remains limited. Our aim was to synthesize literature on pre-stroke frailty and stroke risk to explore their relationship and impact on prognosis. A systematic search of multiple databases was conducted to identify cohort studies published until October 28, 2023. Meta-analysis was conducted using a random effects model. Heterogeneity was assessed with the I² statistic, and publication bias was evaluated using Begg's test. Finally, we included 11 studies (n = 1,660,328 participants). The pooled hazard ratios (HRs) for stroke risk associated with pre-stroke frailty compared to non-frail individuals was 1.72 (95% confidence interval, CI: 1.46-2.02, p = 0.002, I2 = 69.2%, Begg's test: p = 0.536). The pooled HRs for mortality and the pooled relative risk (RRs) modified Rankin Scale (mRs) associated with pre-stroke frailty were 1.68 (95% CI: 1.10-2.56, p = 0.136, I2 = 49.9%, Begg's test: p = 0.296) and 3.11 (95% CI: 1.77-5.46, p = 0.192, I2 = 39.4%, Begg's test: p = 1.000), respectively. In conclusion, pre-stroke frailty is strongly associated with stroke risk and impacts its prognosis, irrespective of the measurement method. Future research should focus on prospective studies to assess the effects of early intervention for frailty. This has significant implications for primary healthcare services and frailty management.


Asunto(s)
Fragilidad , Accidente Cerebrovascular , Anciano , Humanos , Anciano Frágil/estadística & datos numéricos , Fragilidad/complicaciones , Fragilidad/epidemiología , Pronóstico , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones
7.
Phys Chem Chem Phys ; 26(37): 24689-24698, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39282755

RESUMEN

Mixed ionic-electronic conductors are widely used as electroactive materials in energy applications. The contact of a mixed conductor with another phase plays a crucial role in charge storage and transport in energy devices. However, the interfacial chemistry at the heterojunctions comprising mixed conductors and its interplay with the bulk chemistry remains imperative yet inadequately understood. This study addresses the fundamentals of space charge effects by exploring the equilibrium situations for contacts consisting of mixed conductors. From the perspective of defect chemistry, and by unifying the bulk and interfacial conditions with the electrochemical potential, our treatment allows for predicting the built-in potential at heterojunctions, profiling the space charge distributions, and evaluating the resulting interfacial charge storage and transport. The treatment can be related to experimental characterization, including coulometric titration, conductivity, and capacitance measurements at electrochemical interfaces in all-solid-state batteries. Besides, our treatment also highlights the significance of size and doping effects in nanocrystalline electrodes. This work provides a comprehensive framework for understanding and engineering the heterojunctions in electrochemical devices.

8.
Molecules ; 29(18)2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39339288

RESUMEN

As one of the leading cancers threatening women's lives and health, breast cancer is challenging to treat and often irreversible in advanced cases, highlighting the critical importance of early detection and intervention. In recent years, fluorescent probe technology, a revolutionary in vivo imaging tool, has gained attention in medical research for its ability to improve tumor visualization significantly. This review focuses on recent advances in intelligent, responsive fluorescent probes, particularly in the field of breast cancer, which are divided into five categories, near-infrared responsive, fluorescein-labeled, pH-responsive, redox-dependent, and enzyme-triggered fluorescent probes, each of which has a different value for application based on its unique biological response mechanism. In addition, this review also covers the strategy of combining fluorescent probes with various anti-tumor drugs, aiming to reveal the possibility of synergistic effects between the two in breast cancer treatment and provide a solid theoretical platform for the clinical translation of fluorescent probe technology, which is expected to promote the expansion of cancer treatment technology.


Asunto(s)
Neoplasias de la Mama , Colorantes Fluorescentes , Humanos , Colorantes Fluorescentes/química , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/diagnóstico , Femenino , Imagen Óptica/métodos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Animales , Concentración de Iones de Hidrógeno
9.
J Inflamm Res ; 17: 5633-5643, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39219813

RESUMEN

Purpose: Visceral adiposity is a significant risk factor for severe COVID-19. However, the impact of the Chinese visceral adiposity index (CVAI) on the efficacy of SARS-CoV-2 vaccines remains poorly understood. This study aims to explore the impact of CVAI on the production of neutralizing antibodies (NAb) in inactivated SARS-CoV-2 vaccines and the potential mechanism, thereby optimizing vaccination guidance. Methods: In this cross-sectional study, 206 health workers (completed two SARS-CoV-2 vaccination on February 8th and March 10th, 2021, respectively) were recruited. All baseline anthropometric parameters of the participants were collected, and venous blood samples were obtained 6 weeks later to measure peripheral innate immune cells, inflammatory cytokines, and NAb titers against SARS-CoV-2. CVAI were calculated according to the formula and divided participants into two groups depending on CVAI median. Results: The median NAb titer among healthcare workers was 12.94 AU/mL, with an efficacy of 87.86% for the SARS-CoV-2 vaccine. NAb titers were lower in the CVAI dysfunction group than in the CVAI reference group (median: 11.40 AU/mL vs 15.57 AU/mL), the hsCRP levels (median: 0.50 mg/L vs 0.30 mg/L) and peripheral monocyte count (mean: 0.47 × 109/L vs 0.42 × 109/L) in the CVAI dysfunction group were higher than in the CVAI reference group. Additionally, CVAI showed positive correlations with hsCRP, monocytes, lymphocytes, and B-lymphocytes, and a negative correlation with NAb titers. Conclusion: CVAI may inhibit SARS-CoV-2 neutralizing antibody expression through inducing immune dysfunction and chronic inflammation. Thus, more attention should be paid to the vaccination for high CVAI population to improve the effectiveness of vaccination, which could provide more robust support for COVID-19 epidemic prevention and control.

10.
ACS Omega ; 9(34): 36518-36530, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39220516

RESUMEN

When Fourier transform (FT) spectrum peaks are overlapped, primary maxima of odd-order derivatives can be used to evaluate their independent intensities. We studied the feasibility of higher odd-order derivatives on Lorentzian peak shape and magnitude peak shape. Simulation studies for FT nuclear magnetic resonance (NMR) spectroscopy demonstrated good results toward quantitative deconvolution of overlapping FT spectrum peaks. Although it is not so desirable to deconvolute special line shapes such as Gaussian, Voigt, and Tsallis profiles, the odd-order derivatives exhibit a bright future compared to even-order derivatives. An application example of practical NMR spectroscopy with ethylbenzene isomers is presented. White Gaussian noises were added to the simulated spectra at two different signal-to-noise ratios (20 and 40). Kauppinen's denoising and smoothing algorithms can effectively remove interference of the noise and help to have good deconvoluting results using the odd-order derivatives. We compared features of our approach with popular deconvolution sharpening algorithms and conducted a comparison study with Kauppinen's Fourier self-deconvolution. Our approach has a better dynamic range of peak intensities and is not sensitive to the sampling rates. Other common deconvolution methods are also discussed briefly.

11.
Heliyon ; 10(16): e35468, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220951

RESUMEN

This study investigates the rampant spread of offensive and derogatory language during the COVID-19 pandemic and aims to mitigate it through machine learning. Employing advanced Large Language Models (LLMs), the research develops a sophisticated framework adept at detecting and transforming abusive and hateful speech. The project begins by meticulously compiling a dataset, focusing specifically on Chinese language abuse and hate speech. It incorporates an extensive list of 30 pandemic-related terms, significantly enriching the resources available for this type of research. A two-tier detection model is then introduced, achieving a remarkable accuracy of 94.42 % in its first phase and an impressive 81.48 % in the second. Furthermore, the study enhances paraphrasing efficiency by integrating generative AI techniques, primarily Large Language Models, with a Latent Dirichlet Allocation (LDA) topic model. This combination allows for a thorough analysis of language before and after modification. The results highlight the transformative power of these methods. They show that the rephrased statements not only reduce the initial hostility but also preserve the essential themes and meanings. This breakthrough offers users effective rephrasing suggestions to prevent the spread of hate speech, contributing to more positive and constructive public discourse.

12.
Biomacromolecules ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289809

RESUMEN

Silica encapsulation under ambient conditions is commonly used to shield protein-based nanosystems from chemical stress. However, encapsulation-induced photo- and structural instabilities at elevated temperatures have been overlooked. Using bovine serum albumin-capped fluorescent gold nanoclusters (BSA-AuNCs) as a model, we demonstrated that chaperone/polymer layer-by-layer complexation can stabilize the template to resist encapsulation-induced fragmentation/reorganization and emission increases at 37 °C or higher temperatures. We first wrapped BSA-AuNCs with α-crystallin chaperones (α-Crys) to gain the highest thermal stability at a 1:50 molar ratio and then enfolded BSA-AuNC/α-Crys with thermoresponsive poly-N-isopropylacrylamide (PNIPAM) at 60 °C to shield silica interaction and increase the chaperone-client protein accessibility. The resulting BSA-AuNC/α-Crys/PNIPAM (BαP) was encapsulated by a sol-gel process to yield BαP-Si (∼80 ± 4.5 nm), which exhibited excellent structural integrity and photostability against chemical and thermal stresses. Moreover, targeted BαP-Si demonstrated prolonged fluorescence stability for cancer cell imaging. This template stabilization strategy for silica encapsulation is biocompatible and applicable to other protein-based nanosystems.

13.
Front Plant Sci ; 15: 1439972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39263419

RESUMEN

Autophagy is a highly conserved process in eukaryotes that is used to recycle the cellular components from the cytoplasm. It plays a crucial function in responding to both biotic and abiotic stress, as well as in the growth and development of plants. Autophagy-related genes (ATG) and their functions have been identified in numerous crop species. However, their specific tasks in potatoes (Solanum tuberosum L.), are still not well understood. This work is the first to identify and characterize the potato StATG18 subfamily gene at the whole-genome level, resulting in a total of 6 potential StATG18 subfamily genes. We analyzed the phylogenetic relationships, chromosome distribution and gene replication, conserved motifs and gene structure, interspecific collinearity relationship, and cis-regulatory elements of the ATG18 subfamily members using bioinformatics approaches. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) analysis suggested that StATG18 subfamily genes exhibit differential expression in various tissues and organs of potato plants. When exposed to heat stress, their expression pattern was observed in the root, stem, and leaf. Based on a higher expression profile, the StATG18a gene was further analyzed under heat stress in potatoes. The subcellular localization analysis of StATG18a revealed its presence in both the cytoplasm and nucleus. In addition, StATG18a altered the growth indicators, physiological characteristics, and photosynthesis of potato plants under heat stresses. In conclusion, this work offers a thorough assessment of StATG18 subfamily genes and provides essential recommendations for additional functional investigation of autophagy-associated genes in potato plants. Moreover, these results also contribute to our understanding of the potential mechanism and functional validation of the StATG18a gene's persistent tolerance to heat stress in potato plants.

15.
BMC Med ; 22(1): 357, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39227839

RESUMEN

BACKGROUND: Our previous genome­wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated. METHODS: We assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms. RESULTS: We identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not < 12. This variant is associated with residual islet function but not islet-specific autoantibody positivity in T1D individuals. Bioinformatics analysis indicated that rs912304 is a functional variant exhibiting spatial overlaps with enhancer active histone marks (H3K27ac and H3K4me1) and open chromatin status (ATAC-seq) in the human pancreas and islet tissues. Luciferase reporter gene assays and eQTL analyses demonstrated that the biallelic sites of rs912304 had differential allele-specific enhancer activity in beta cell lines and regulated STXBP6 expression, which was defined as the most putative causal gene based on Open Targets Genetics, GTEx v8 and Tiger database. Moreover, Stxbp6 was upregulated by T1D-related proinflammatory cytokines but not high glucose/fat. Notably, Stxbp6 over-expressed INS-1E cells exhibited decreasing insulin secretion and increasing cell apoptosis through Glut1 and Gadd45ß, respectively. CONCLUSIONS: This study expanded the genomic landscape regarding late-onset T1D risk and supported islet function mechanistically connected to T1D pathogenesis.


Asunto(s)
Diabetes Mellitus Tipo 1 , Islotes Pancreáticos , Humanos , Diabetes Mellitus Tipo 1/genética , Islotes Pancreáticos/metabolismo , Femenino , Masculino , Polimorfismo de Nucleótido Simple/genética , Predisposición Genética a la Enfermedad , Citocinas/genética , Citocinas/metabolismo , Niño , Adolescente , Sitios de Carácter Cuantitativo , Animales , Edad de Inicio , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo
16.
Biomaterials ; 314: 122835, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39276409

RESUMEN

Induction of reactive oxygen species (ROS) production in cancer cells plays a critical role for cancer treatment. However, therapeutic efficiency remains challenging due to insufficient ROS production of current ROS inducers. We designed a novel platinum (Pt)-based drug named "carrier-platin" that integrates ultrasmall Pt-based nanoparticles uniformly confined within a poly(amino acids) carrier. Carrier-platin dramatically triggered a burst of ROS in cancer cells, leading to cancer cell death as quick as 30 min. Unlike traditional Pt-based drugs which induce cell apoptosis through DNA intercalation, carrier-platin with superior ROS catalytic activities induces a unique pattern of cancer cell death that is neither apoptosis nor ferroptosis and operates independently of DNA damage. Importantly, carrier-platin demonstrates superior anti-tumor efficacy against a broad spectrum of cancers, particularly those with multidrug resistance, while maintaining minimal systemic toxicity. Our findings reveal a distinct mechanism of action of Pt in cancer cell eradication, positioning carrier-platin as a novel category of anti-cancer chemotherapeutics.

17.
Front Med (Lausanne) ; 11: 1453609, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39301491

RESUMEN

Objective: To determine the comparative effects and safety of traditional Chinese medicine (TCM) interventions based on meridian theory for pain relief in patients with primary dysmenorrhea (PD). Methods: This is a systematic review with network meta-analysis. Randomized controlled trials (RCTs) comparing meridian-based TCM interventions with waitlist, placebo, western medicine, and conventional therapies for PD pain. A SUCRA was used to estimate the probability ranking for the effects of interventions. Results: 57 RCTs involving 3,903 participants and 15interventions were included. Thirty-two RCTs were rated as low risk of bias. A network diagram was drawn with 105 pairs of comparisons. Compared with NSAIDs and waitlist, significantly better effects were found in acupressure [SMD = -1.51, 95%CI (-2.91, -0.12)/SMD = -2.31, 95%CI (-4.61, -0.02)], warm needling [SMD = -1.43, 95%CI (-2.68, -0.18)/SMD = -2.23, 95%CI (-4.43, -0.03)], moxibustion [SMD = -1.21, 95%CI (-1.85, -0.57)/SMD = -2.10, 95%CI (-3.95, -0.07)], and acupuncture [SMD = -1.09, 95%CI (-1.62, -0.55)/SMD = -1.89, 95%CI (-3.67, -0.11)]. No adverse events were detected. Conclusion: For PD pain, the effects of acupressure, acupuncture, warm needling, and moxibustion were superior to those of NSAIDs and waitlist. Oral contraceptive pill, electro-acupuncture, acupressure, and warm needling demonstrated higher probabilities of being better interventions. More high-quality clinical trials are needed to provide more robust evidence of this network. Systematic review registration: PROSPERO CRD42022373312.

18.
Viruses ; 16(9)2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39339971

RESUMEN

During the COVID-19 pandemic, the monitoring of SARS-CoV-2 RNA in wastewater was used to track the evolution and emergence of variant lineages and gauge infection levels in the community, informing appropriate public health responses without relying solely on clinical testing. As more sublineages were discovered, it increased the difficulty in identifying distinct variants in a mixed population sample, particularly those without a known lineage. Here, we compare the sequencing technology from Illumina and from Oxford Nanopore Technologies, in order to determine their efficacy at detecting variants of differing abundance, using 248 wastewater samples from various Quebec and Ontario cities. Our study used two analytical approaches to identify the main variants in the samples: the presence of signature and marker mutations and the co-occurrence of signature mutations within the same amplicon. We observed that each sequencing method detected certain variants at different frequencies as each method preferentially detects mutations of distinct variants. Illumina sequencing detected more mutations with a predominant lineage that is in low abundance across the population or unknown for that time period, while Nanopore sequencing had a higher detection rate of mutations that are predominantly found in the high abundance B.1.1.7 (Alpha) lineage as well as a higher sequencing rate of co-occurring mutations in the same amplicon. We present a workflow that integrates short-read and long-read sequencing to improve the detection of SARS-CoV-2 variant lineages in mixed population samples, such as wastewater.


Asunto(s)
COVID-19 , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , SARS-CoV-2 , Aguas Residuales , Aguas Residuales/virología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/clasificación , COVID-19/virología , COVID-19/diagnóstico , COVID-19/epidemiología , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , ARN Viral/genética , Ontario/epidemiología , Quebec , Secuenciación de Nanoporos/métodos , Genoma Viral
19.
Int J Mol Sci ; 25(18)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39337691

RESUMEN

Vitexin (VTX), a C-glycosylated flavone found in various medicinal herbs, is known for its antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the protective effects of VTX against orofacial dyskinesia (OD) in rats, induced by haloperidol (HPD), along with the neuroprotective mechanisms underlying these effects. OD was induced by administering HPD (1 mg/kg i.p.) to rats for 21 days, which led to an increase in the frequency of vacuous chewing movements (VCMs) and tongue protrusion (TP). VTX (10 and 30 mg/kg) was given intraperitoneally 60 min after each HPD injection during the same period. On the 21st day, following assessments of OD, the rats were sacrificed, and nitrosative and oxidative stress, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptosis markers in the striatum were measured. HPD effectively induced OD, while VTX significantly reduced HPD-induced OD, decreased oxidative stress, enhanced antioxidant capacity, prevented mitochondrial dysfunction, and reduced neuroinflammatory and apoptotic markers in the striatum, and the protective effects of VTX on both behavioral and biochemical aspects of HPD-induced OD were significantly reduced when trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated pathway, was administered. These findings suggest that VTX provides neuroprotection against HPD-induced OD, potentially through the Nrf2 pathway, indicating its potential as a therapeutic candidate for the prevention or treatment of tardive dyskinesia (TD) in clinical settings. However, further detailed research is required to confirm these preclinical findings and fully elucidate VTX's therapeutic potential in human studies.


Asunto(s)
Apigenina , Haloperidol , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Haloperidol/farmacología , Haloperidol/efectos adversos , Ratas , Apigenina/farmacología , Masculino , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Transducción de Señal/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Apoptosis/efectos de los fármacos , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Discinesia Inducida por Medicamentos/metabolismo , Cuerpo Estriado/metabolismo , Cuerpo Estriado/efectos de los fármacos
20.
Nat Commun ; 15(1): 7169, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169013

RESUMEN

Protein complexes are fundamental to all cellular processes, so understanding their evolutionary history and assembly processes is important. Gene duplication followed by divergence is considered a primary mechanism for diversifying protein complexes. Nonetheless, to what extent assembly of present-day paralogous complexes has been constrained by their long evolutionary pathways and how cross-complex interference is avoided remain unanswered questions. Subunits of protein complexes are often stabilized upon complex formation, whereas unincorporated subunits are degraded. How such cooperative stability influences protein complex assembly also remains unclear. Here, we demonstrate that subcomplexes determined by cooperative stabilization interactions serve as building blocks for protein complex assembly. We further develop a protein stability-guided method to compare the assembly processes of paralogous complexes in cellulo. Our findings support that oligomeric state and the structural organization of paralogous complexes can be maintained even if their assembly processes are rearranged. Our results indicate that divergent assembly processes by paralogous complexes not only enable the complexes to evolve new functions, but also reinforce their segregation by establishing incompatibility against deleterious hybrid assemblies.


Asunto(s)
Complejos Multiproteicos , Complejos Multiproteicos/metabolismo , Complejos Multiproteicos/química , Complejos Multiproteicos/genética , Estabilidad Proteica , Evolución Molecular , Subunidades de Proteína/metabolismo , Subunidades de Proteína/química , Multimerización de Proteína , Unión Proteica , Duplicación de Gen
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