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1.
Sci Rep ; 14(1): 22794, 2024 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354143

RESUMO

This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C < 100 mg/dL. This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke patients who treated with statin before index stroke and LDL-C < 100 mg/dL on admission. Non-traditional lipid profiles including non-HDL, TC/HDL ratio, LDL/HDL ratio, and TG/HDL ratio were analyzed as a continuous or categorical variable. The primary vascular outcome within one year was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction (MI) and all-cause mortality. Hazard ratios (95% Cis) for 1-year vascular outcomes were analyzed using the Cox PH model for each non-traditional lipid profiles groups. A total of 7028 patients (age 70.3 ± 10.8years, male 59.8%) were finally analyzed for the study. In unadjusted analysis, no significant associations were observed in the quartiles of LDL/HDL ratio and 1-year primary outcome. However, after adjustment of relevant variables, compared with Q1 of the LDL/HDL ratio, Q4 was significantly associated with increasing the risk of 1-year primary outcome (HR 1.48 [1.19-1.83]). For the LDL/HDL ratio, a linear relationship was observed (P for linearity < 0.001). Higher quartiles of the LDL/HDL ratio were significantly and linearly associated with increasing the risk of 1-year primary vascular outcomes. These findings suggest that even during statin therapy with LDL-C < 100 mg/dl on admission, there should be consideration for residual risk based on the LDL/HDL ratio, following stroke.


Assuntos
LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Humanos , Masculino , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , AVC Isquêmico/sangue , AVC Isquêmico/tratamento farmacológico , LDL-Colesterol/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Idoso de 80 Anos ou mais , Lipídeos/sangue , Sistema de Registros , Infarto do Miocárdio/sangue , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológico
2.
Biomaterials ; 314: 122842, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39383778

RESUMO

Exploring host cell specificity, pathogenicity, and molecular mechanisms of the vacuolating cytotoxin A (VacA), secreted by Helicobacter pylori (Hp) is crucial for developing novel treatment strategies. VacA affects subcellular events, particularly mitochondria, at a cell-type-specific level. However, the lack of reliable models that mimic VacA-induced subcellular damages and enable novel drug screening linked to the human stomach clinically limits our understanding of the mitochondrial networks in vivo. Here, human antrum gastric organoids (hAGOs) and tissue samples from Hp-infected patients were used to show the toxic effects of VacA-induced mitochondrial damage mainly in mucus-producing gastric pit cells by employing transcriptional, translational, and functional analyses. In VacA-intoxicated or Hp-infected hAGOs, robust mitochondrial fragmentation in gastric pit cells reduced ATP production during respiration, and loss of mucosal barrier integrity was first demonstrated experimentally. Using hAGOs, clinically relevant small molecules were screened for efficacy, and MLN8054, an Aurora kinase A inhibitor, reversed VacA-induced mitochondrial damage and loss of gastric epithelium integrity. MLN8054 was effective in VacA-treated and Hp-infected hAGOs and mice, highlighting hAGOs as a promising drug-screening model. These findings suggest that mitochondrial quality control may serve as a promising therapeutic target for Hp VacA-mediated toxicity and disease progression.

3.
Sci Adv ; 10(40): eadp9885, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39365868

RESUMO

Melanogenesis, a natural responsive mechanism of human skin to harmful radiation, is a self-triggered defensive neural activity safeguarding the body from radiation exposure in advance. With the increasing significance of radiation shielding in diverse medical health care and wearable applications, a biomimetic neuromorphic optoelectronic system with adaptive radiation shielding capability is often needed. Here, we demonstrate a transparent and flexible metal oxide-based photovoltaic neuromorphic defensive system. By using a monolithically integrated ultraflexible optoelectronic circuitry and electrochromic device, seamless neural processing for ultraviolet (UV) radiation shielding including history-based sensing, memorizing, risk recognition, and blocking can be realized with piling the entire signal chain into the flexible devices. The UV shielding capability of the system can be evaluated as autonomous blocking up to 97% of UV radiation from 5 to 90 watts per square meter in less than 16.9 seconds, demonstrating autonomously modulated sensitivity and response time corresponding to UV environmental conditions and supplied bias.


Assuntos
Biomimética , Raios Ultravioleta , Humanos , Biomimética/métodos , Proteção Radiológica/instrumentação , Proteção Radiológica/métodos , Dispositivos Eletrônicos Vestíveis , Pele/efeitos da radiação , Materiais Biomiméticos
4.
Rev Cardiovasc Med ; 25(9): 332, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39355602

RESUMO

Background: High sodium and low potassium consumption are related to hypertension and cardiovascular disease. We aimed to determine the relationship between the frequency of salt addition and potassium consumption with the risk of new-onset atrial fibrillation (AF). Methods: Our study used the UK Biobank cohort, which included over 500,000 individuals enrolled from the United Kingdom between 2006 and 2010. This study involved 416,868 participants who filled out the dietary recall regarding the frequency of salt addition. Results: During follow-up, 19,164 (4.6%) developed AF. The incidence of new-onset AF was increased based on the frequency of salt addition (never/rarely 3.83; always 4.72 per 1000 person-years). Compared with the group that never/rarely added salt, those adding salt always were at significantly higher risk of incident AF after adjusting for multiple variables (hazard ratio (HR) 1.15; 95% confidence interval (CI) 1.06-1.24), and additional adjustment of dietary and total energy consumption (HR 1.37; 95% CI 1.08-1.73). In the subgroup analysis, the risk of AF incident according to the frequency of salt addition significantly increased in low urine potassium levels compared to high (p for interaction = 0.046). In the subgroup analysis for AF patients, higher salt addition frequency was related to increased all-cause mortality. Conclusions: Our study demonstrated that adding salt to foods more frequently increases the risk of incident AF, even after adjusting for dietary and total energy consumption. In the high urine potassium group, the impact of high sodium consumption on incident AF was attenuated.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39375903

RESUMO

Assessment of the clock genes, Period (Per) 1, Per2, Per3, and Cryptochrome (Cry) 2, Cry3, and Cry4, can help better understand eel spawning ecology. In this study, the circadian rhythm and moonlight effects of these clock genes in the eel retina and hypothalamus were analyzed. We examined clock gene expression patterns under 12 h light:12 h darkness (12L12D), constant darkness (DD), and constant light (LL) conditions; under short photoperiod (SP; 9L15D) and long photoperiod (LP; 15L9D), and during the new moon (NM) and full moon in male eels. Per2 expression increased after sunrise, Cry2, and Cry4 expression increased around sunset, and Per1, Per3, and Cry3 expression increased before sunrise. Under SP conditions, oscillations of retinal Per3 and Cry4, which did not occur under LP conditions, were generated. In addition, retinal Cry4 oscillation was generated under NM conditions. These results suggest that the retina of the eel may play an important role in regulating circadian rhythm, and migration is initiated by the synchronization of clock genes by moonlight, suggesting that photic signals are closely related to the migratory activity of the eel.

6.
Adv Sci (Weinh) ; : e2408028, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382149

RESUMO

Ovonic threshold switching (OTS) selectors based on amorphous chalcogenides can revolutionize 3D memory technology owing to their self-selecting memory (SSM) behavior. However, the complex mechanism governing the memory writing operation limits compositional and device optimization. This study investigates the mechanism behind the polarity-dependent threshold voltage shift (ΔVTH) through theoretical and experimental analyses. By examining the physical principles of threshold switching and conducting defect state analysis, the ΔVTH as a memory window is confirmed to be attributed to the dynamics of charged defects and their gradient near electrodes, influenced by the nonuniform electric field after threshold switching. This study provides critical insights into the operational mechanism of OTS-based SSM, known as selector-only memory, highlighting its advantages for developing high-density, low-cost, and energy-efficient memory technologies in the artificial intelligence era.

7.
Neurospine ; 21(3): 868-877, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39363467

RESUMO

Recent advances in robotics technology and artificial intelligence (AI) have sparked increased interest in humanoid robots that resemble humans and social robots capable of interacting socially. Alongside this trend, a new field of robot research called human-robot interaction (HRI) is gaining prominence. The aim of this review paper is to introduce the fundamental concepts of HRI and social robots, examine their current applications in the medical field, and discuss the current and future prospects of HRI and social robots in spinal care. HRI is an interdisciplinary field where robotics, AI, social sciences, design, and various disciplines collaborate organically to develop robots that successfully interact with humans as the ultimate goal. While social robots are not yet widely deployed in clinical environments, ongoing HRI research encompasses various areas such as nursing and caregiving support, social and emotional assistance, rehabilitation and cognitive enhancement for the elderly, medical information provision and education, as well as patient monitoring and data collection. Although still in its early stages, research related to spinal care includes studies on robotic support for rehabilitation exercises, assistance in gait training, and questionnaire-based assessments for spinal pain. Future applications of social robots in spinal care will require diverse HRI research efforts and active involvement from spinal specialists.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39377235

RESUMO

BACKGROUND AND OBJECTIVES: The number of people with dementia and the burden on families to care for them are increasing. As a result, families are affected in their use of time to carry out daily activities. This study compared family caregivers of dementia patients (dementia family) and non-family caregivers of dementia patients (non-dementia family), reflecting their characteristics on weekdays and weekends. METHODS: There were 92 participants each in the groups dementia family and non-dementia family. Each group was divided into 121 people on weekdays and 71 people on weekends. Time usage was measured by occupational area. The variables assessed were "lack of time," "tiredness," "life satisfaction," and "leisure satisfaction." Variables including "house chores sharing" and "role division" were also assessed. The time usage of the Korea National Statistical Office's 2019 "time use survey" was reclassified based on the occupational areas of the Occupational Therapy Practice Framework-Fourth Edition, and time usage and satisfaction were analyzed. Frequency analysis and independent t-test were used for statistical processing. RESULTS: On weekdays, the dementia family showed less time usage in the "leisure" area for men and "social participation" area for women than the non-dementia family. On weekends, dementia family showed less time usage in the "activities of daily living" (ADLs) area than the non-dementia family and women in dementia family showed less time usage in "ADLs" area compared to women in the non-dementia family. Satisfaction was found to be higher in terms of "lack of time" and "tiredness" on weekdays and "tiredness" on weekends in dementia family than in the non-dementia family. CONCLUSIONS: Time usage and satisfaction of dementia family and non-dementia family showed differences during weekdays and weekends. These results suggest that for family caregivers of dementia patients, it is necessary to improve the efficient use of time and satisfaction during weekdays and holidays.

9.
Exp Mol Med ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39363111

RESUMO

Single-cell technologies have enhanced comprehensive knowledge regarding the human brain by facilitating an extensive transcriptomic census across diverse brain regions. Nevertheless, understanding the cellular and temporal specificity of neurological disorders remains ambiguous due to developmental variations. To address this gap, we illustrated the dynamics of disorder risk gene expression under development by integrating multiple single-cell RNA sequencing datasets. We constructed a comprehensive single-cell atlas of the developing human brain, encompassing 393,060 single cells across diverse developmental stages. Temporal analysis revealed the distinct expression patterns of disorder risk genes, including those associated with autism, highlighting their temporal regulation in different neuronal and glial lineages. We identified distinct neuronal lineages that diverged across developmental stages, each exhibiting temporal-specific expression patterns of disorder-related genes. Lineages of nonneuronal cells determined by molecular profiles also showed temporal-specific expression, indicating a link between cellular maturation and the risk of disorder. Furthermore, we explored the regulatory mechanisms involved in early brain development, revealing enriched patterns of fetal cell types associated with neuronal disorders indicative of the prenatal stage's influence on disease determination. Our findings facilitate unbiased comparisons of cell type‒disorder associations and provide insight into dynamic alterations in risk genes during development, paving the way for a deeper understanding of neurological disorders.

10.
Sci Rep ; 14(1): 22940, 2024 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-39358448

RESUMO

Effective antihypertensive therapy is essential for achieving optimal blood pressure (BP) control and reducing cardiovascular events. This double-blind, multicenter, randomized trial aimed to compare the antihypertensive efficacy and safety of a combination of amlodipine (AML) and candesartan cilexetil (CC) versus AML monotherapy in patients with essential hypertension (HTN). After a 4-week run-in period with AML 5 mg, patients whose HTN remained uncontrolled (diastolic BP [DBP]) ≥ 90 mmHg and < 120 mmHg) were randomized to receive either AML + CC or AML alone for 8 weeks. Efficacy was assessed by measuring changes in DBP and systolic BP (SBP). The primary safety measure was the incidence of adverse events (AEs). A total of 174 participants were included in the efficacy analysis. After 8 weeks, DBP decreased by -9.92 ± 0.86 mmHg in the AML + CC arm and - 2.08 ± 0.86 mmHg in the AML arm (p < 0.0001). SBP decreased by -14.27 ± 1.39 mmHg in the AML + CC arm versus - 2.77 ± 1.39 mmHg in the AML arm (p < 0.0001). AEs occurred in 11.24% of the AML + CC group and 5.62% of the AML group (p = 0.1773). AML + CC combination therapy demonstrated superior efficacy with good tolerance, making it a promising option for patients with inadequately controlled hypertension on amlodipine alone.


Assuntos
Anlodipino , Anti-Hipertensivos , Benzimidazóis , Compostos de Bifenilo , Pressão Sanguínea , Quimioterapia Combinada , Hipertensão , Tetrazóis , Humanos , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anlodipino/uso terapêutico , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/efeitos adversos , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos , Tetrazóis/uso terapêutico , Hipertensão/tratamento farmacológico , Método Duplo-Cego , Pressão Sanguínea/efeitos dos fármacos , Idoso , Resultado do Tratamento , Hipertensão Essencial/tratamento farmacológico , Adulto
11.
BMC Microbiol ; 24(1): 404, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39390387

RESUMO

BACKGROUND: Preventing post-weaning diarrhea (PWD) in weaned piglets is a crucial challenge in the swine production industry. The stress of weaning, dietary shifts from maternal milk to solid feed, and environmental changes lead to decreased microbial diversity, increased pathogen abundance, and compromised intestinal integrity. We have previously identified Lactiplantibacillus argentoratensis AGMB00912 (LA) in healthy porcine feces, which demonstrated antimicrobial activity against pathogens and enhanced short-chain fatty acid production. This research aimed to evaluate the efficacy of LA strain supplementation as a strategy to inhibit PWD and enhance overall growth performance in weaned piglets. RESULTS: LA supplementation in weaned piglets significantly increased body weight gain, average daily gain, and average daily feed intake. It also alleviated diarrhea symptoms (diarrhea score and incidence). Notably, LA was found to enrich beneficial microbial populations (Lactobacillus, Anaerobutyricum, Roseburia, Lachnospiraceae, and Blautia) while reducing the abundance of harmful bacteria (Helicobacter and Campylobacter). This not only reduces the direct impact of pathogens but also improves the overall gut microbiota structure, thus enhancing the resilience of weaned piglets. LA treatment also promotes the growth of the small intestinal epithelial structure, strengthens gut barrier integrity, and increases short-chain fatty acid levels in the gut. CONCLUSIONS: The study findings demonstrate the promising potential of LA in preventing PWD. Supplementation with the LA strain offers a promising feed additive for improving intestinal health and growth in piglets during the weaning transition, with the potential to significantly reduce the incidence and severity of PWD.


Assuntos
Ração Animal , Diarreia , Microbioma Gastrointestinal , Probióticos , Doenças dos Suínos , Desmame , Animais , Suínos , Diarreia/microbiologia , Diarreia/veterinária , Diarreia/prevenção & controle , Doenças dos Suínos/microbiologia , Doenças dos Suínos/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Ração Animal/análise , Fezes/microbiologia , Lactobacillaceae/genética , Lactobacillaceae/crescimento & desenvolvimento , Aumento de Peso/efeitos dos fármacos , Suplementos Nutricionais
12.
Nurs Open ; 11(10): e2175, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39390805

RESUMO

AIM: To evaluate nurses' workload during the coronavirus disease 2019 (COVID-19) pandemic and to identify their perception of medical serviced robots (MSRs) that may help with or replace the tasks of nurses in negative-pressure isolated wards and general wards. DESIGN: Cross-sectional survey. METHODS: A researcher-made questionnaire was applied that assessed nurses' current workload and their attitudes towards and perceptions of MSRs. A visual analogue scale (VAS) from 1 to 10 was used to assess workload. Perceptions evaluated on a 5-point Likert scale ranging from one point for 'strongly disagree' to five points for 'strongly agree'. A higher VAS score indicated a higher workload. On the other hands, a higher Likert score indicated a more positive perception and three points was neutral. The questionnaire was conducted on 150 nurses in negative-pressure isolated wards for the management of COVID-19 and 150 nurses in general wards. Quota sampling technique was used as sampling technique. Data analysis was performed through independent t-tests, chi-square tests and two-tailed tests. The p-value <0.05 was interpreted to statistically significant. RESULTS: Two hundred eighty-two participants responded and 142 belonged to the negative-pressure isolated ward. The overall response rate was 94%, and 94.7% in the negative isolated ward. The mean score ± standard deviation for nursing-related psychological stress at the current work site was 7.18 ± 1.58 points, and the mean score for physical workload was 7.65 ± 1.48. The need for MSRs was rated as 3.66 ± 0.86 out of 5. Overall, a positive attitude towards MSRs was confirmed, with no difference between ward groups. The overall ratings were 3.14 ± 1.15 for perceived availability and 3.26 ± 1.13 for perceived efficiency. Both nurse groups perceived that MSRs were most available and efficient for monitoring and measurements. Nurses in negative-pressure isolated wards perceived MSRs more positively than did nurses in general wards regarding setting of alarms (p = 0.003) and delivery of medical devices/materials (p = 0.013). Based on these results, functional development of MSRs associated with monitoring, measurements, setting of alarms and delivery should be prioritized. No patient or public contribution.


Assuntos
Atitude do Pessoal de Saúde , COVID-19 , Recursos Humanos de Enfermagem Hospitalar , Robótica , Carga de Trabalho , Humanos , Estudos Transversais , COVID-19/psicologia , Feminino , Masculino , Inquéritos e Questionários , Carga de Trabalho/psicologia , Adulto , Recursos Humanos de Enfermagem Hospitalar/psicologia , SARS-CoV-2 , Pessoa de Meia-Idade , Pandemias
13.
Vaccines (Basel) ; 12(9)2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39339996

RESUMO

In South Korea, a mandatory nation-wide foot-and-mouth disease (FMD) vaccination policy is in place. However, a major side effect of the current method of intramuscular (IM) administration of oil-adjuvanted FMD vaccines is the formation of granulomas in the muscles of pigs. To address this issue, we assessed the possible application of intradermal (ID) vaccination. Initially, we compared the serological immune response in specific pathogen-free pigs inoculated with FMD vaccines formulated with eight different adjuvants, administered twice at the neck site using a syringe with a needle via the ID route. Among the formulations (water-in-oil-in-water (W/O/W), oil-in-water (O/W), and polymer nanomaterials), ISA 207 of W/O/W was the most effective in inducing immunogenicity followed by ISA 201 of W/O/W. ISA 207 was further tested in formulations of different antigen doses (12 or 1.2 µg) delivered via both IM and ID routes. All four treatments successfully protected the pigs against FMD virus challenges. To assess the feasibility of the field application of the vaccines with ISA 207, we conducted ID vaccination of conventional pigs using a needle-free device, resulting in the detection of significant levels of neutralizing antibodies. ISA 207 was shown to be superior to ISA 201 in inducing immunogenicity via the ID route. In conclusion, ISA 207 could be a suitable adjuvant for ID vaccination in terms of vaccine efficacy for FMD, allowing for alternate use of ID vaccination and subsequent reduction in the incidences of granuloma formation in the field.

14.
Nutrition ; 128: 112565, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39326237

RESUMO

OBJECTIVES: This study investigated the therapeutic potential of Lactobacillus plantarum NCHBL-004 (NCHBL-004) in the treatment of obesity and associated metabolic disorders. METHODS: Mice were fed either a normal diet (ND) or a high-fat diet (HFD) with oral administration of NCHBL-004. After euthanasia, blood, liver and adipose tissue were collected. Furthermore, the microbiome and short-chain fatty acids (SCFAs) were analyzed from feces. RESULTS: Oral administration of live NCHBL-004 to mice fed a HFD resulted in notable reductions in weight gain, improvements in glucose metabolism, and maintenance of balanced lipid levels. A comparative analysis with other Lactobacillus strains highlighted the superior efficacy of NCHBL-004. Moreover, heat-killed NCHBL-004 demonstrated beneficial effects similar to those of live NCHBL-004. Additionally, administration of live NCHBL-004 induced glucagon-like peptide 1 (GLP-1) production and increased the levels of short-chain fatty acids (SCFAs), including acetate and propionate, in feces, positively influencing liver lipid metabolism and mitigating inflammation. Consistent with this, analysis of the gut microbiome following NCHBL-004 administration showed increases in SCFA-producing microbes with increased proportions of Lactobacillus spp. and a significant increase in the proportion of microbes capable of promoting GLP-1 secretion. CONCLUSIONS: These findings underscore the potential of both live and inactivated NCHBL-004 as potential therapeutic approaches to managing obesity and metabolic disorders, suggesting avenues for further investigation and clinical applications.

15.
medRxiv ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39314968

RESUMO

Immune checkpoint blockade (ICB) is the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), yet efficacy remains low. The current approach for predicting the likelihood of response to ICB is a single proportional biomarker (PD-L1) expressed in immune and tumor cells (Combined Positive Score, CPS) without differentiation by cell type, potentially explaining its limited predictive value. Tertiary Lymphoid Structures (TLS) have shown a stronger association with ICB response than PD-L1. However, their exact composition, size, and spatial biology in HNSCC remain understudied. A detailed understanding of TLS is required for future use as a clinically applicable predictive biomarker. Methods: Pre-ICB tumor tissue sections were obtained from 9 responders (complete response, partial response, or stable disease) and 11 non-responders (progressive disease) classified via RECISTv1.1. A custom multi-immunofluorescence (mIF) staining assay was designed, optimized, and applied to characterize tumor cells (pan-cytokeratin), T cells (CD4, CD8), B cells (CD19, CD20), myeloid cells (CD16, CD56, CD163), dendritic cells (LAMP3), fibroblasts (α Smooth Muscle Actin), proliferative status (Ki67) and immunoregulatory molecules (PD1). Spatial metrics were compared among groups. Serial tissue sections were scored for TLS in both H&E and mIF slides. A machine learning model was employed to measure the effect of these metrics on achieving a response to ICB (SD, PR, or CR). Results: A higher density of B lymphocytes (CD20+) was found in responders compared to non-responders to ICB (p=0.022). A positive correlation was observed between mIF and pathologist identification of TLS (R 2 = 0.66, p-value= <0.0001). TLS trended toward being more prevalent in responders to ICB (p=0.0906). The presence of TLS within 100 µm of the tumor was associated with improved overall (p=0.04) and progression-free survival (p=0.03). A multivariate machine learning model identified TLS density as a leading predictor of response to ICB with 80% accuracy. Conclusion: Immune cell densities and TLS spatial location within the tumor microenvironment play a critical role in the immune response to HNSCC and may potentially outperform CPS as a predictor of ICB response.

16.
Biomolecules ; 14(9)2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39334958

RESUMO

Cartilage, a critical tissue for joint function, often degenerates due to osteoarthritis (OA), rheumatoid arthritis (RA), and trauma. Recent research underscores necroptosis, a regulated form of necrosis, as a key player in cartilage degradation. Unlike apoptosis, necroptosis triggers robust inflammatory responses, exacerbating tissue damage. Key mediators such as receptor-interacting serine/threonine-protein kinase-1 (RIPK1), receptor-interacting serine/threonine-protein kinase-3(RIPK3), and mixed lineage kinase domain-like (MLKL) are pivotal in this process. Studies reveal necroptosis contributes significantly to OA and RA pathophysiology, where elevated RIPK3 and associated proteins drive cartilage degradation. Targeting necroptotic pathways shows promise; inhibitors like Necrostatin-1 (Nec-1), GSK'872, and Necrosulfonamide (NSA) reduce necroptotic cell death, offering potential therapeutic avenues. Additionally, autophagy's role in mitigating necroptosis-induced damage highlights the need for comprehensive strategies addressing multiple pathways. Despite these insights, further research is essential to fully understand necroptosis' mechanisms and develop effective treatments. This review synthesizes current knowledge on necroptosis in cartilage degeneration, aiming to inform novel therapeutic approaches for OA, RA, and trauma.


Assuntos
Necroptose , Osteoartrite , Humanos , Necroptose/efeitos dos fármacos , Animais , Osteoartrite/patologia , Osteoartrite/metabolismo , Osteoartrite/tratamento farmacológico , Cartilagem/patologia , Cartilagem/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Artrite Reumatoide/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/tratamento farmacológico , Autofagia , Proteínas Quinases/metabolismo , Imidazóis , Indóis
17.
Animals (Basel) ; 14(18)2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39335322

RESUMO

Duck hepatitis A virus type 1 (DHAV-1) is the main pathogen causing viral hepatitis in ducks, marked by high contagion and acute mortality. Live attenuated DHAV-1 vaccines are widely used to control the disease. This study aims to develop a mismatch amplification mutation assay (MAMA)-PCR for the rapid detection and differentiation of Korean DHAV-1 wild-type strains from vaccine strains. A MAMA primer was designed to target a single nucleotide polymorphism (SNPs) at position 2276 within the VP1 gene, allowing differentiation in a single PCR reaction. The MAMA-PCR accurately identified both strains, with detection limits of 100.5 ELD50/mL and 102.3 ELD50/mL, respectively. The MAMA-PCR demonstrated specificity, showing no cross-reactivity with 12 other viral and bacterial pathogens. The MAMA-PCR was applied to 89 farms, yielding results consistent with nested-PCR and sequence determination, identifying four positive farms for DHAV-1 vaccine strains. In conclusion, this study is the first to employ the MAMA-PCR method to distinguish between DHAV-1 wild-type and vaccine strains. The developed method is rapid, simple, specific, and sensitive, thereby serving as an effective tool for clinical diagnostics in identifying and differentiating between Korean DHAV-1 wild-type and vaccine strains.

18.
Toxics ; 12(9)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39330561

RESUMO

In this study, we developed and validated a multiresidue analytical method for the simultaneous detection of 24 pesticides in fishery products. Using the EN15662 extraction method and C18 as the adsorbent for purification, the validation results complied with Codex guidelines, achieving recovery rates between 70% and 120% and relative standard deviation values (%RSD) within 20%, indicating excellent performance. The limit of detection ranged from 0.25 to 0.8 ng/kg, and the limit of quantification was between 3 and 10 ng/g, providing sufficient sensitivity to comply with future regulatory standards. The calibration curves for all 24 pesticides exhibited great linearity (R2 > 0.98), also satisfying the Codex requirements. The matrix effect was less than 30% for some pesticides-within ±20%-indicating minimal interference from impurities. An analysis of 300 fishery samples from nine regions across South Korea detected lufenuron at 10 ng/g in eels; however, the risk assessment was below 0.19%, posing no significant hazard to public health. This newly developed analytical method proved effective for the multi-analysis of pesticide residues in fishery products, offering rapid and reliable monitoring of the import and export safety of fishery products.

19.
Sci Total Environ ; 954: 176438, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307361

RESUMO

The objectives of this study were to produce biochars using sulfur-rich acidified lignin discharged from a biorefinery process and to evaluate their physicochemical properties and Pb adsorption capacity. As the pyrolysis temperature increased, the lignin acidified by the desulfurization process was converted to neutralized biochar (LBC), which exhibited high carbon content and stability. The carbon content of biochar manufactured at a pyrolysis temperature of 600 °C or higher was over 90 % and showed no significant difference, and their surface structures were found to be different, as revealed through XRD and FTIR analyses. The adsorption capacity of Pb by LBC increased with increasing pyrolysis temperature, and their adsorption capacity was well described by the pseudo-second-order model and the Langmuir isotherm adsorption model. In particular, the internal diffusion effect on the adsorption capacity of Pb was greater for LBC900 than for LBC600. In complex heavy metal solutions, LBC selectively exhibited high affinity for Pb, while the adsorption capacity of other metals was significantly reduced. The adsorption mechanism of Pb by LBC was verified through various analytical methods, and these results demonstrated that the adsorption of Pb by LBC was influenced by functional groups existing on the surface and inside of LBC and by some cation exchange.

20.
PLoS One ; 19(9): e0310708, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39312563

RESUMO

In 2009, Lyubashevsky proposed a lattice-based signature scheme using the Schnorr-like identification and the Fiat-Shamir heuristic and proved its security under the collision resistance of a generalized compact knapsack function. However, their security analysis requires the witness indistinguishability property, leading to significant inefficiency and an increase of sizes of public key and signature. To overcome the efficiency issue associated with the WI property, we introduce a new lattice-based assumption, called the target-modified one-wayness problem of the GCK function and show its reduction to well-known lattice-based problems. Additionally, we present a simple and efficient GCK-based signature scheme, GCKSign, whose security is based on the Module GCK-TMO problem in the random oracle model. GCKSign is a natural extension of Lyubashevsky's scheme in a module setting, but achieves considerable efficiency gains due to eliminating the witness indistinguishability property. As a result, GCKSign achieves approximately 3.4 times shorter signature size and 2.4 times shorter public key size at the same security level.


Assuntos
Segurança Computacional , Algoritmos , Modelos Teóricos
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