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1.
Artículo en Inglés | MEDLINE | ID: mdl-39275965

RESUMEN

Monzogranite is known for its high surface area and cation exchange capacity, which play a crucial role in ameliorating the challenges by enhancing nutrient adsorption and facilitating nutrient availability during the weaning period. Weaned crossbred piglets (Duroc × Yorkshire × Landrace), initially weighing 5.36 ± 0.26 kg, were allocated into four treatments with 6 replicates each (10 pigs per replicate). The treatments encompassed CON (basal diet), Z0.1 (0.1% monzogranite supplementation in basal diet), Z0.2 (0.2% monzogranite supplementation), and Z0.3 (0.3% monzogranite supplementation). In phase 1, a linear increase in total average daily gain (ADG) was observed across treatment groups, with a concomitant linear increase in ADG and gain-to-feed ratio (G/F). The overall results showed a linear increase in ADG and G/F. A linear decrease in aspartate aminotransferase and lactate dehydrogenase levels was observed across treatment groups. Conversely, no significant differences were noted in the levels of albumin, alkaline phosphatase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, blood urea nitrogen, triglycerides, and gamma-glutamyl transferase among the treatment groups. Faecal scoring indicated a linear reduction in scores at Day 7 among the treatment groups. However, no significant differences were observed at Days 14 and 28. The assessment of immunoglobulins demonstrated a significant increase in both immunoglobulin G and immunoglobulin A levels in the Z0.1 treatment group compared to the CON. In both phase 1 and phase 2, a linear decrease in cortisol levels was evident. In conclusion, a linear increase in total ADG and G/F during phase 1, sustained across both phases, suggests monzogranite potential to enhance growth performance. Moreover, stress mitigation was shown through a consistent linear decrease in cortisol levels across phases. These findings underscore monzogranite multifaceted impact, emphasizing its potential as a dietary supplement to enhance growth, liver health, and stress resilience in weanling pigs.

2.
Skin Res Technol ; 30(9): e70055, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39300791

RESUMEN

BACKGROUND: Solar lentigo, a common epidermal hyperpigmented lesion found in sun-exposed areas, results from the proliferation of melanocytes and the accumulation of melanin. Although various treatments for solar lentigo have been explored, they often lead to complications, including prolonged erythema and post-inflammatory hyperpigmentation (PIH), posing significant concerns. OBJECTIVES AND METHODS: This study evaluated the safety and efficacy of the Vasculature Salvage Laser Surgery (VSLS) system. We treated six Korean patients, each with solar lentigo, in a single session using the 532-nm nanosecond neodymium-doped yttrium aluminum garnet (Nd:YAG) VSLS system, with follow-up periods ranging from 3 to 10 weeks. RESULTS: The treatment led to the complete removal of pigmented lesions in all patients without resulting in PIH, even in cases where previous laser treatments had failed. The only side effect observed was mild erythema, which resolved over the long term in most instances. CONCLUSIONS: The VSLS system emerges as a safe and effective treatment for pigmented lesions, including refractory solar lentigines. Nonetheless, additional studies are required to verify its long-term efficacy.


Asunto(s)
Láseres de Estado Sólido , Lentigo , Humanos , Femenino , Láseres de Estado Sólido/uso terapéutico , Lentigo/cirugía , Masculino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Anciano , Terapia por Láser/métodos , Terapia por Láser/instrumentación , Luz Solar/efectos adversos , Hiperpigmentación/cirugía
3.
IUCrJ ; 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39297240

RESUMEN

MltG, a membrane-bound lytic transglycosylase, has roles in terminating glycan polymerization in peptidoglycan and incorporating glycan chains into the cell wall, making it significant in bacterial cell-wall biosynthesis and remodeling. This study provides the first reported MltG structure from Mycobacterium abscessus (maMltG), a superbug that has high antibiotic resistance. Our structural and biochemical analyses revealed that MltG has a flexible peptidoglycan-binding domain and exists as a monomer in solution. Further, the putative active site of maMltG was disclosed using structural analysis and sequence comparison. Overall, this study contributes to our understanding of the transglycosylation reaction of the MltG family, aiding the design of next-generation antibiotics targeting M. abscessus.

4.
BMC Psychol ; 12(1): 467, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223598

RESUMEN

BACKGROUND: As non-face-to-face contact has become a daily routine owing to the development of science and technology and impact of the coronavirus disease (COVID-19) pandemic, online technology-based services (TBSSs) have been expanding. Consequently, in virtual metaverse exercise spaces, the number of participants using TBSS is increasing. This study aimed to examine the effects of TBSS characteristics on the quality of the relationship between service providers and users of metaverse exercise services. METHODS: The participants were metaverse exercise service users in Korea, who were selected through purposive sampling (n = 254, 194 men, 61 women). A questionnaire survey was conducted to measure the participants' TBSS characteristics (enjoyment, stability, usefulness, ease of use, and reliability) and relationship quality (satisfaction, trust, and commitment). We analyzed the frequency, validity, reliability, and descriptive statistics of the collected data. Moreover, correlation and multivariate multiple regression analyses were conducted. RESULTS: Enjoyment, stability, usefulness, and reliability of TBSS had positive effects on satisfaction; however, ease of use did not have a significant effect. In addition, enjoyment, usefulness, ease of use, and reliability of TBSS had positive effects on trust; however, stability did not have a significant effect. Furthermore, enjoyment and reliability of TBSS had positive effects on commitment; however, usefulness, ease of use, and stability had no significant effects. CONCLUSIONS: This study provides metaverse exercise service providers with management strategies for attracting and retaining members. The results of this study could help develop effective TBSS and aid metaverse service companies facing a fiercely competitive environment.


Asunto(s)
COVID-19 , Humanos , Masculino , Femenino , República de Corea , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Ciclismo , Adulto Joven , Confianza , SARS-CoV-2
5.
Science ; 385(6713): eadi1650, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39236183

RESUMEN

Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 (KRT9) expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency. Given fibroblasts' capacity to modify keratinocyte differentiation, we hypothesized that volar fibroblasts influence these features. Bioprinted skin constructs confirmed the capacity of volar fibroblasts to induce volar keratinocyte features. A clinical trial of healthy volunteers demonstrated that injecting volar fibroblasts into nonvolar skin increased volar features that lasted up to 5 months, highlighting a potential cellular therapy.


Asunto(s)
Refuerzo Biomédico , Bioimpresión , Dermis , Epidermis , Fibroblastos , Queratinocitos , Adulto , Femenino , Humanos , Masculino , Amputados , Diferenciación Celular , Colágeno/metabolismo , Dermis/citología , Dermis/metabolismo , Elastina/metabolismo , Epidermis/metabolismo , Fibroblastos/citología , Fibroblastos/trasplante , Mano , Queratina-9/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Refuerzo Biomédico/métodos
6.
Cell Commun Signal ; 22(1): 425, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223652

RESUMEN

BACKGROUND: Increased cancer stem cell (CSC) content and SOX2 overexpression are common features in the development of resistance to therapy in hormone-dependent breast cancer, which remains an important clinical challenge. SOX2 has potential as biomarker of resistance to treatment and as therapeutic target, but targeting transcription factors is also challenging. Here, we examine the potential inhibitory effect of different polyoxometalate (POM) derivatives on SOX2 transcription factor in tamoxifen-resistant breast cancer cells. METHODS: Various POM derivatives were synthesised and characterised by infrared spectra, powder X-ray diffraction pattern and nuclear magnetic resonance spectroscopy. Estrogen receptor (ER) positive breast cancer cells, and their counterparts, which have developed resistance to the hormone therapy tamoxifen, were treated with POMs and their consequences assessed by gel retardation and chromatin immunoprecipitation to determine SOX2 binding to DNA. Effects on proliferation, migration, invasion and tumorigenicity were monitored and quantified using microscopy, clone formation, transwell, wound healing assays, flow cytometry and in vivo chick chorioallantoic membrane (CAM) models. Generation of lentiviral stable gene silencing and gene knock-out using CRISPR-Cas9 genome editing were applied to validate the inhibitory effects of the selected POM. Cancer stem cell subpopulations were quantified by mammosphere formation assays, ALDEFLUOR activity and CD44/CD24 stainings. Flow cytometry and western blotting were used to measure reactive oxygen species (ROS) and apoptosis. RESULTS: POMs blocked in vitro binding activity of endogenous SOX2. [P2W18O62]6- (PW) Wells-Dawson-type anion was the most effective at inhibiting proliferation in various cell line models of tamoxifen resistance. 10 µM PW also reduced cancer cell migration and invasion, as well as SNAI2 expression levels. Treatment of tamoxifen-resistant cells with PW impaired tumour formation by reducing CSC content, in a SOX2-dependent manner, which led to stem cell depletion in vivo. Mechanistically, PW induced formation of reactive oxygen species (ROS) and inhibited Bcl-2, leading to the death of tamoxifen-resistant cells. PW-treated tamoxifen-resistant cells showed restored sensitivity to tamoxifen. CONCLUSIONS: Together, these observations highlight the potential use of PW as a SOX2 inhibitor and the therapeutic relevance of targeting SOX2 to treat tamoxifen-resistant breast cancer.


Asunto(s)
Neoplasias de la Mama , Resistencia a Antineoplásicos , Factores de Transcripción SOXB1 , Tamoxifeno , Compuestos de Tungsteno , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción SOXB1/genética , Tamoxifeno/farmacología , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Femenino , Compuestos de Tungsteno/farmacología , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Línea Celular Tumoral , Animales
7.
Small ; : e2406249, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221532

RESUMEN

Aqueous Zn-ion batteries (AZIBs) are promising energy-storage devices owing to their exceptional safety, long cycle life, simple production, and high storage capacity. Manganese oxides are considered potential cathode materials for AZIBs, primarily because of their safety, low cost, simple synthesis, and high storage capacity. However, MnO2-based cathodes tend to deteriorate structurally during long-term cycling, which reduces their reversible capacity. In this study, an advanced α-MnO2@SnO2 nanocomposite via facile hydrothermal synthesis is developed. The synergistic effects of lattice disorder and increased electron conductivity in the α-MnO2@SnO2 nanocomposite mitigate structural degradation and enhance the overall electrochemical performance. The nanocomposite exhibits a high reversible capacity of 347 mAh g-1 at a current density of 100 mA g-1 after 50 cycles. Furthermore, it exhibits excellent rate performance and stable capacity even after 1000 cycles, maintaining a capacity of 78 mAh g-1 at a high current density of 5 A g-1. This excellent electrochemical performance is attributed to the reversible Zn intercalation in α-MnO2@SnO2 nanocomposites due to the increased structural stability and fast ion/electron exchange caused by the distortion of the tunnel structure, on the basis of various ex situ experiments, density functional theory calculations, and electrochemical characterizations.

8.
Eur J Med Chem ; 277: 116764, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39180945

RESUMEN

Motile cilia are crucial for maintaining healthy bodily functions by facilitating fluid transport and removing foreign substances or debris from the body. The dysfunction of motile cilia leads to ciliopathy. In particular, damage to the motile cilia of the airways can cause or worsen respiratory disease, making it an attractive target for therapeutic interventions. However, there are no treatments to induce motile ciliogenesis. Forkhead box transcription factor J1 (FOXJ1), the master regulator, has been implicated in motile cilia formation. Mice lacking the Foxj1 gene show loss of axoneme, a key component of cilia, that further highlights the importance of FOXJ1 in motile cilia formation. This prompted us to identify new small molecules that could induce motile ciliogenesis. A phenotype-based high-throughput screening (HTS) in a Tg(foxj1a:eGFP) zebrafish model was performed and a novel hit compound was identified. Among the synthesized compounds, compound 16c effectively enhanced motile ciliogenesis in a transgenic zebrafish model. To further test the efficacy of compound 16c on a mammalian airway system consisting of multiciliated cells (MCCs), ex vivo mice tracheal epithelial cell culture was adopted under an air-liquid interface system (ALI). Compound 16c significantly increased the number of MCCs by enhancing motile ciliogenesis. In addition, compound 16c exhibited good liver microsomal stability, in vivo PK profiles with AUC, and oral bioavailability. There was no significant inhibition of CYP and hERG, and no cell cytotoxicity was shown. In an elastase-induced COPD (chronic obstructive pulmonary disease) mouse model, compound 16c effectively prevented the development and onset of COPD. Taken together, compound 16c has great promise as a therapeutic agent for treating and alleviating motile ciliopathies.


Asunto(s)
Cilios , Descubrimiento de Drogas , Piridinas , Pez Cebra , Animales , Cilios/efectos de los fármacos , Cilios/metabolismo , Ratones , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Humanos , Relación Estructura-Actividad , Estructura Molecular , Animales Modificados Genéticamente , Factores de Transcripción Forkhead/metabolismo , Relación Dosis-Respuesta a Droga
9.
Curr Issues Mol Biol ; 46(8): 9136-9148, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39194757

RESUMEN

Skin healing occurs through an intricate process called wound healing which comprises four phases: coagulation and hemostasis, inflammation, cellular proliferation, and remodeling. Chronic wounds often arise because of prolonged or excessive inflammation, which hinders the healing process and wound closure. Despite the recognized efficacy of Pogostemon cablin (patchouli) in wound healing, the precise mechanism of action of Pogostemon cablin extract (PCE) on inflammation and wound healing remains poorly understood. In this study, we investigated the effects of PCE on cell proliferation and wound healing, as well as its anti-inflammatory activity, using in vitro experiments. We found that PCE increased cell proliferation and expression of the cell proliferation marker Ki67 and accelerated wound healing in human keratinocytes through the activation of OR2AT4. Furthermore, PCE exhibited anti-inflammatory effects by decreasing the levels of pro-inflammatory cytokines interleukin-6 and -8 in lipopolysaccharide-treated and TNF-α-exposed THP-1 and HaCaT cells, respectively. Overall, these findings suggest that PCE holds therapeutic potential by promoting cell proliferation, facilitating wound healing, and exerting anti-inflammatory effects.

10.
PLoS One ; 19(8): e0300090, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39186484

RESUMEN

BAKGROUND: To evaluate the quantitative and qualitative image quality using deep learning image reconstruction (DLIR) of pediatric cardiac computed tomography (CT) compared with conventional image reconstruction methods. METHODS: Between January 2020 and December 2022, 109 pediatric cardiac CT scans were included in this study. The CT scans were reconstructed using an adaptive statistical iterative reconstruction-V (ASiR-V) with a blending factor of 80% and three levels of DLIR with TrueFidelity (low-, medium-, and high-strength settings). Quantitative image quality was measured using signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). The edge rise distance (ERD) and angle between 25% and 75% of the line density profile were drawn to evaluate sharpness. Qualitative image quality was assessed using visual grading analysis scores. RESULTS: A gradual improvement in the SNR and CNR was noted among the strength levels of the DLIR in sequence from low to high. Compared to ASiR-V, high-level DLIR showed significantly improved SNR and CNR (P<0.05). ERD decreased with increasing angle as the level of DLIR increased. CONCLUSION: High-level DLIR showed improved SNR and CNR compared to ASiR-V, with better sharpness on pediatric cardiac CT scans.


Asunto(s)
Aprendizaje Profundo , Relación Señal-Ruido , Tomografía Computarizada por Rayos X , Humanos , Niño , Tomografía Computarizada por Rayos X/métodos , Femenino , Preescolar , Masculino , Procesamiento de Imagen Asistido por Computador/métodos , Lactante , Corazón/diagnóstico por imagen , Adolescente , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Recién Nacido
11.
Nucleic Acids Res ; 52(17): 10563-10574, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39180405

RESUMEN

CRISPR-Cas systems function as adaptive immune mechanisms in bacteria and archaea and offer protection against phages and other mobile genetic elements. Among many types of CRISPR-Cas systems, Type I CRISPR-Cas systems are most abundant, with target interference depending on a multi-subunit, RNA-guided complex known as Cascade that recruits a transacting helicase nuclease, Cas3, to degrade the target. While structural studies on several other types of Cas3 have been conducted long ago, it was only recently that the structural study of Type I-C Cas3 in complex with Cascade was revealed, shedding light on how Cas3 achieve its activity in the Cascade complex. In the present study, we elucidated the first structure of standalone Type I-C Cas3 from Neisseria lactamica (NlaCas3). Structural analysis revealed that the histidine-aspartate (HD) nuclease active site of NlaCas3 was bound to two Fe2+ ions that inhibited its activity. Moreover, NlaCas3 could cleave both single-stranded and double-stranded DNA in the presence of Ni2+ or Co2+, showing the highest activity in the presence of both Ni2+ and Mg2+ ions. By comparing the structural studies of various Cas3 proteins, we determined that our NlaCas3 stays in an inactive conformation, allowing us to understand the structural changes associated with its activation and their implication.


Asunto(s)
Proteínas Asociadas a CRISPR , Sistemas CRISPR-Cas , Proteínas Asociadas a CRISPR/metabolismo , Proteínas Asociadas a CRISPR/química , Proteínas Asociadas a CRISPR/genética , Dominio Catalítico , Modelos Moleculares , Neisseria/genética , Neisseria/enzimología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Cristalografía por Rayos X , ADN/metabolismo , ADN/química , ADN/genética , Unión Proteica
12.
J Hazard Mater ; 478: 135359, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39126856

RESUMEN

Polyhexamethylene guanidine (PHMG) is a positively charged polymer used as a disinfectant that kills microbes but can cause pulmonary fibrosis if inhaled. After the long-term risks were confirmed in South Korea, it became crucial to measure toxicity through diverse surrogate biomarkers, not only proteins, especially after these hazardous chemicals had cleared from the body. These biomarkers, identified by their biological functions rather than simple numerical calculations, effectively explained the imbalance of pulmonary surfactant caused by fibrosis from PHMG exposure. These long-term studies on children exposed to PHMG has shown that blood protein indicators, primarily related to apolipoproteins and extracellular matrix, can distinguish the degree of exposure to humidifier disinfectants (HDs). We defined the extreme gradient boosting models and computed reflection scores based on just ten selected proteins, which were also verified in adult women exposed to HD. The reflection scores successfully discriminated between the HD-exposed and unexposed groups in both children and adult females (AUROC: 0.957 and 0.974, respectively) and had a strong negative correlation with lung function indicators. Even after an average of more than 10 years, blood is still considered a meaningful specimen for assessing the impact of environmental exposure to toxic substances, with proteins providing in identifying the pathological severity of such conditions.


Asunto(s)
Aerosoles , Proteínas Sanguíneas , Guanidinas , Humanos , Guanidinas/toxicidad , Guanidinas/química , Femenino , Adulto , Proteínas Sanguíneas/análisis , Lesión Pulmonar/inducido químicamente , Biomarcadores/sangre , Desinfectantes/toxicidad , Niño , Humidificadores , Exposición por Inhalación/efectos adversos
13.
Biochem Biophys Rep ; 39: 101779, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39099605

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) or Dabie bandavirus is an emerging pathogen responsible for SFTS. It is considered a novel threat to human health, given the high associated fatality. SFTSV is a segmented negative-strand RNA virus containing three single-stranded RNAs, with the M segment encoding the glycoproteins Gn and Gc. Gc is vital for viral entry into the host cell surface, along with the Gn protein. As the Gc is the surface-exposable antigen from virions, it is a critical diagnostic marker of infection. Although various SFTSV Gn or N protein-based sero-diagnostic methods have been developed, there are no commercially available sero-diagnostic kits. Therefore, we generated monoclonal antibodies (mAbs) against SFTSV Gc and explored their application in serum diagnostic tests to develop sensitive serodiagnostic tools covering broad-range genotypes (A to F). First, 10 SFTSV Gc antibody-binding fragments (Fabs) were isolated using a phage display system and converted into human IgGs. Enzyme-linked immunosorbent assays (ELISA) of the SFTSV and Rift Valley fever virus (RVFV: same genus as SFTSV) Gc antigens showed that all antibodies attached to the SFTSV Gc protein had high affinity. An immunofluorescence assay (IFA), to verify the cross-reactivity of seven antibodies with high affinities for various SFTSV genotypes (A, B2, B3, D, and F) and detect mAb binding with intact Gc proteins, revealed that five IgG type mAbs were bound to intact Gc proteins of various genotypes. Six high-affinity antibodies were selected using ELISA and IFA. The binding capacity of the six antibodies against the SFTSV Gc antigen was measured using surface plasmon resonance. All antibodies had high binding capacity. Consequently, these antibodies serve as valuable markers in the serological diagnosis of SFTSV.

14.
Pediatr Cardiol ; 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217235

RESUMEN

The volumetric data obtained from the cardiac CT scan of congenital heart disease patients is important for defining patient's status and making decision for proper management. The objective of this study is to evaluate the intra-observer, inter-observer, and interstudy reproducibility of left ventricular (LV) and right ventricular (RV) or functional single-ventricle (FSV) volume. And compared those between manual and using semi-automated segmentation tool. Total of 127 patients (56 female, 71 male; mean age 82.1 months) underwent pediatric protocol cardiac CT from January 2020 to December 2022. The volumetric data including both end-systolic and -diastolic volume and calculated EF were derived from both conventional semiautomatic region growing algorithms (CM, TeraRecon, TeraRecon, Inc., San Mateo, CA, USA) and deep learning-based annotation program (DLS, Medilabel, Ingradient, Inc., Seoul, Republic of Korea) by three readers, who have different background knowledge or experience of radiology or image extraction before. The reproducibility was compared using intra- and inter-observer agreements. And the usability was measured using time for reconstruction and number of tests that were reconfigured before the reconfiguration time was reduced to less than 5 min. Inter- and intra-observer agreements showed better agreements degrees in DLS than CM in all analyzers. The time used for reconstruction showed significantly shorter in DLS compared with CM. And significantly small numbers of tests before the reconfiguration is needed in DLS than CM. Deep learning-based annotation program can be more accurate way for measurement of volumetric data for congenital heart disease patients with better reproducibility than conventional method.

15.
Biochem Biophys Res Commun ; 733: 150573, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39208644

RESUMEN

In bacteria, the ankyrin-like protein AnkB helps overcome stress by regulating catalase activity when expressed under stressful conditions. As the structural properties of AnkB are largely unexplored, our understanding of various AnkB-mediated functions in bacteria remains limited. In the present study, we describe the structure of AnkB from Acinetobacter baumannii, hereafter referred to as "AbAnkB," which has a unique tertiary configuration compared with that of other ankyrin domain-containing proteins. Structural analysis revealed that AbAnkB has a relatively long loop between AKR3 and AKR4 and an oppositely positioned α8 helix. Based on amino acid conservation and protein surface analyses, we identified a hydrophobic patch that might be critical for the function of AbAnkB. To the best of our knowledge, our study is the first to report the structure of a bacterial AnkB protein; our findings will markedly enhance our understanding of its functions in bacteria.

16.
Mol Ther ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39169624

RESUMEN

Cytotoxic T lymphocytes (CTLs) play a crucial role in cancer rejection. However, CTLs encounter dysfunction and exhaustion in the immunosuppressive tumor microenvironment (TME). Although the reactive oxygen species (ROS)-rich TME attenuates CTL function, the underlying molecular mechanism remains poorly understood. The nuclear factor erythroid 2-related 2 (Nrf2) is the ROS-responsible factor implicated in increasing susceptibility to cancer progression. Therefore, we examined how Nrf2 is involved in anti-tumor responses of CD8+ T and chimeric antigen receptor (CAR) T cells in the ROS-rich TME. Here, we demonstrated that tumor growth in Nrf2-/- mice was significantly controlled and was reversed by T cell depletion and further confirmed that Nrf2 deficiency in T cells promotes anti-tumor responses using an adoptive transfer model of antigen-specific CD8+ T cells. Nrf2-deficient CTLs are resistant to ROS, and their effector functions are sustained in the TME. Furthermore, Nrf2 knockdown in human CAR-T cells enhanced the survival and function of intratumoral CAR-T cells in a solid tumor xenograft model and effectively controlled tumor growth. ROS-sensing Nrf2 inhibits the anti-tumor T cell responses, indicating that Nrf2 may be a potential target for T cell immunotherapy strategies against solid tumors.

17.
Medicina (Kaunas) ; 60(8)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39202645

RESUMEN

Background and Objectives: This study aimed to investigate the clinical course and characteristics of late toxicity over time following the completion of definitive radiotherapy (RT) in patients with cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 60 patients with cervical cancer who underwent pelvic external beam radiotherapy followed by intracavitary brachytherapy. Late toxicity was assessed for the lower gastrointestinal (GI) tract and bladder organ at 6, 12, 24, 36, and >36 months post-RT. We examined the onset and prevalence of late toxicity at each time point. Clinical remission and interventions for managing late toxicity were also investigated. Results: The peak onset of lower GI toxicity occurred 12 months after RT completion, with a median symptom duration of 9.9 months (range, 0.1-26.3 months), and exhibited its highest prevalence rate of 15.5% at 24 months post-RT. Most GI toxicities developed and resolved within three years post-RT, with a prevalence rate of 8.1% at three years, followed by a decreasing trend. Bladder toxicity first peaked at 24 months post-RT and continued to occur beyond 36 months, showing the re-increasing pattern in the prevalence rate after 36 months (23.5%). In terms of clinical remission, 66.7% of lower GI toxicities (12 of 18 patients) and 60% of bladder toxicities (9 of 15 patients) achieved complete remission by the last follow-up date. Conclusions: Late toxicities of the GI and bladder following definitive RT in cervical cancer are partially reversible and exhibit distinct patterns of onset and prevalence over time. A systematic follow-up strategy should be established for the early detection and timely intervention of late toxicity by understanding these clinical courses.


Asunto(s)
Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/radioterapia , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/etiología , Braquiterapia/efectos adversos , Braquiterapia/métodos , Factores de Tiempo , Vejiga Urinaria/efectos de la radiación , Vejiga Urinaria/lesiones , Tracto Gastrointestinal/efectos de la radiación , Tracto Gastrointestinal/lesiones , Anciano de 80 o más Años
18.
ACS Nano ; 18(34): 23320-23330, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39151093

RESUMEN

The high interface resistance at the cathode-sulfide electrolyte interface is still a crucial drawback in an all-solid-state battery, unlike the initial expectation that the all-solid-state interface would enhance electrochemical stability by reducing side reactions at the interface. In this study, we examined the fundamental mechanism of unexpected reactions at the interface of LiNi0.8Co0.1Mn0.1O2 (NCM811) and argyrodite (Li6PS5Br0.5Cl0.5, LPSBC) sulfide solid electrolytes based on the combined method of multiscale simulations and electrochemical experiments. The high interface resistance originates from the formation of a passivating layer at the interface combined with irregular atomic and electronic structures, Li depletion, mutual element exchange, and mechanical contact loss between the oxide cathode and sulfide solid electrolyte. We also confirmed that these side reactions were suppressed by O substitutions to sulfide solid electrolyte (LPSOBC), and then the chemo-mechanical stability of the all-solid battery was enhanced by alleviating the side reactions at the interface. This study provides rational insights into the design of an interface for all-solid-state batteries.

19.
Microbiol Spectr ; : e0366823, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162551

RESUMEN

Latilactobacillus sakei is an important bacterial species used as a starter culture for fermented foods; however, two subspecies within this species exhibit different properties in the foods. Matrix-assisted laser desorption/ionization-time of flight mass spectrometer (MALDI-TOF MS) is the gold standard for microbial fingerprinting. However, the resolution power is down to the species level. This study was to combine MALDI-TOF mass spectra and machine learning to develop a new method to identify two L. sakei subspecies (L. sakei subsp. sakei and L. sakei subsp. carnosus) and non-L. sakei species. Totally, 227 strains were collected, with 908 spectra obtained via on- and off-plate protein extraction. Only 68.7% of strains were correctly identified at the subspecies level in the Biotyper database; however, a high level of performance was observed from the machine learning models. Partial least squares-discriminant analysis (PLS-DA), principal component analysis-K-nearest neighbor (PCA-KNN), and support vector machine (SVM) demonstrated 0.823, 0.914, and 0.903 accuracies, respectively, whereas the random forest (RF) achieved an accuracy of 0.954, with an area under the receiver operating characteristic (AUROC) curve of 0.99, outperforming the other algorithms in distinguishing the subspecies. The machine learning proved to be a promising technique for the rapid and high-resolution classification of L. sakei subspecies using MALDI-TOF MS. IMPORTANCE: Latilactobacillus sakei plays a significant role in the realm of food bacteria. One particular subspecies of L. sakei is employed as a protective agent during food fermentation, whereas another strain is responsible for food spoilage. Hence, it is crucial to precisely differentiate between the two subspecies of L. sakei. In this study, machine learning models based on protein mass peaks were developed for the first time to distinguish L. sakei subspecies. Furthermore, the efficacy of three commonly used machine learning algorithms for microbial classification was evaluated. Our results provide the foundation for future research on developing machine learning models for the classification of microbial species or subspecies. In addition, the developed model can be used in the food industry to monitor L. sakei subspecies in fermented foods in a time- and cost-effective method for food quality and safety.

20.
J Clin Med ; 13(16)2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39200940

RESUMEN

Background/Objectives: Hospital-associated disability (HAD), a functional decline following acute hospitalization, is a common complication associated with mortality and unfavorable prognoses in patients admitted to acute care hospitals. However, few studies have investigated mortality and associated factors in patients with HAD and have been limited by inconsistent HAD assessment tools and criteria. This study investigated mortality and risk factors in patients with HAD using specific criteria. Methods: This retrospective study evaluated patients referred to the Department of Rehabilitation Medicine with suspected HAD between June 2022 and March 2023. The collected data included medical histories, diagnostic tests for HAD (including muscle strength, balance, and modified Barthel Index), and bioelectrical impedance analysis (BIA). Multivariate logistic regression analysis was conducted to identify factors associated with mortality. Kaplan-Meier survival curves were constructed for mortality at 3 and 7 months. Results: A total of 455 patients were identified, among which 206 patients diagnosed with HAD (73.1 ± 12.5 years) were included in the analysis. The 3-month mortality rate was 27.2%. In the multivariate analysis, male sex (odds ratio (OR), 3.23; p < 0.01), a history of cancer (OR, 2.18; p < 0.05), and a low phase angle (OR, 0.69; p < 0.05) were significantly associated with mortality. A phase angle < 2.9° on BIA was associated with a significant increase in 3-month (hazard ratio (HR), 1.85; 95% confidence interval (CI), 1.06-3.23) and 7-month (HR, 2.80; 95% CI, 1.75-4.98) mortality. Conclusions: Patients with HAD had a high mortality rate, with several factors, particularly low BIA phase angles, associated with increased mortality.

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