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1.
World J Clin Cases ; 12(18): 3417-3427, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983437

RESUMEN

BACKGROUND: The emergency department (ED) plays a critical role in establishing artificial airways and implementing mechanical ventilation. Managing airbags in the ED presents a prime opportunity to mitigate the risk of ventilator-associated pneumonia. Nonetheless, existing research has largely overlooked the understanding, beliefs, and practical dimensions of airway airbag management among ED nurses, with a predominant focus on intensive care unit nurses. AIM: To investigate the current status of ED nurses' knowledge, beliefs, and practical behaviors in airway airbag management and their influencing factors. METHODS: A survey was conducted from July 10th to August 10th, 2023, using convenience sampling on 520 ED nurses from 15 tertiary hospitals and 5 sary hospitals in Shanghai. Pathway analysis was utilized to analyze the influencing factors. RESULTS: The scores for ED nurses' airway airbag management knowledge were 60.26 ± 23.00, belief was 88.65 ± 13.36, and behavior was 75.10 ± 19.84. The main influencing factors of airbag management knowledge included participation in specialized nurse or mechanical ventilation training, department, and work experience in the department. Influencing factors of airbag management belief comprised knowledge, department, and participation in specialized nurse or mechanical ventilation training. Primary influencing factors of airbag management behavior included knowledge, belief, department, participation in specialized nurse or mechanical ventilation training, and professional title. The belief in airbag management among ED nurses acted as a partial mediator between knowledge and behavior, with a total effect value of 0.513, and an indirect effect of 0.085, constituting 16.6% of the total effect. CONCLUSION: ED nurses exhibit a positive attitude toward airbag management with relatively standardized practices, yet there remains room for improvement in their knowledge levels. Nursing managers should implement interventions tailored to the characteristics of ED nurses' airbag management knowledge, beliefs, and practices to enhance their airbag management proficiency.

2.
J Transl Med ; 22(1): 671, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033101

RESUMEN

BACKGROUND: The molecular mechanisms underlying nonalcoholic fatty liver disease (NAFLD) remain to be fully elucidated. Ubiquitin specific protease 13 (USP13) is a critical participant in inflammation-related signaling pathways, which are linked to NAFLD. Herein, the roles of USP13 in NAFLD and the underlying mechanisms were investigated. METHODS: L02 cells and mouse primary hepatocytes were subjected to free fatty acid (FFA) to establish an in vitro model reflective of NAFLD. To prepare in vivo model of NAFLD, mice fed a high-fat diet (HFD) for 16 weeks and leptin-deficient (ob/ob) mice were used. USP13 overexpression and knockout (KO) strategies were employed to study the function of USP13 in NAFLD in mice. RESULTS: The expression of USP13 was markedly decreased in both in vitro and in vivo models of NAFLD. USP13 overexpression evidently inhibited lipid accumulation and inflammation in FFA-treated L02 cells in vitro. Consistently, the in vivo experiments showed that USP13 overexpression ameliorated hepatic steatosis and metabolic disorders in HFD-fed mice, while its deficiency led to contrary outcomes. Additionally, inflammation was similarly attenuated by USP13 overexpression and aggravated by its deficiency in HFD-fed mice. Notably, overexpressing of USP13 also markedly alleviated hepatic steatosis and inflammation in ob/ob mice. Mechanistically, USP13 bound to transforming growth factor ß-activated kinase 1 (TAK1) and inhibited K63 ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways and promoting insulin signaling pathways. Inhibition of TAK1 activation reversed the exacerbation of NAFLD caused by USP13 deficiency in mice. CONCLUSIONS: Our findings indicate the protective role of USP13 in NAFLD progression through its interaction with TAK1 and inhibition the ubiquitination and phosphorylation of TAK1. Targeting the USP13-TAK1 axis emerges as a promising therapeutic strategy for NAFLD treatment.


Asunto(s)
Dieta Alta en Grasa , Quinasas Quinasa Quinasa PAM , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico , Proteasas Ubiquitina-Específicas , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Quinasas Quinasa Quinasa PAM/metabolismo , Proteasas Ubiquitina-Específicas/metabolismo , Humanos , Masculino , Activación Enzimática , Inflamación/patología , Ratones Noqueados , Ratones , Hepatocitos/metabolismo , Línea Celular , Ubiquitinación
3.
World J Gastroenterol ; 30(22): 2893-2901, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38947295

RESUMEN

BACKGROUND: This study employed a phenomenological research approach within qualitative research to explore the challenges encountered by elderly individuals with temporary colostomies in managing their daily lives and care needs. Protecting the anus surgery combined with temporary colostomy has emerged as a prevalent treatment modality for low rectal cancer. However, the ileostomy is susceptible to peri-stoma skin complications, as well as fluid, electrolyte, and nutritional imbalances, posing challenges to effective management. The successful self-management of patients is intricately linked to their adjustment to temporary colostomy; nonetheless, there remains a dearth of research examining the factors influencing self-care among temporary colostomy patients and the obstacles they confront. AIM: To investigate the lived experiences, perceptions, and care requirements of temporary colostomy patients within their home environment, with the ultimate goal of formulating a standardized management protocol. METHODS: Over the period of June to August 2023, a purposive sampling technique was utilized to select 12 patients with temporary intestinal stomas from a tertiary hospital in Shanghai, China. Employing a phenomenological research approach, a semi-structured interview guide was developed, and qualitative interviews were conducted using in-depth interview techniques. The acquired data underwent coding, analysis, organization, and summarization following Colaizzi's seven-step method. RESULTS: The findings of this study revealed that the experiences and needs of patients with temporary intestinal stomas can be delineated into four principal themes: Firstly, Temporary colostomy patients bear various burdens and concerns about the uncertainty of disease progression; secondly, patients exhibit limited self-care capabilities and face information deficits, resulting in heightened reliance on healthcare professionals; thirdly, patients demonstrate the potential for internal motivation through proactive self-adjustment; and finally, patients express a significant need for emotional and social support. CONCLUSION: Home-living patients with temporary intestinal stomas confront multifaceted challenges encompassing burdens, inadequate self-care abilities, informational deficits, and emotional needs. Identifying factors influencing patients' self-care at home and proposing strategies to mitigate barriers can serve as a foundational framework for developing and implementing nursing interventions tailored to the needs of patients with temporary intestinal stomas.


Asunto(s)
Colostomía , Investigación Cualitativa , Autocuidado , Humanos , Femenino , Anciano , Masculino , Colostomía/psicología , China/epidemiología , Persona de Mediana Edad , Anciano de 80 o más Años , Ileostomía/psicología , Ileostomía/efectos adversos , Calidad de Vida , Entrevistas como Asunto , Neoplasias del Recto/psicología , Neoplasias del Recto/cirugía , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Adaptación Psicológica
4.
Ecol Evol ; 14(7): e11621, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39026961

RESUMEN

Pulex simulans and Polygenis gwyni are vectors of many flea-borne diseases. They were widely recorded in the United States and Mexico between 1970 and 2000. Maximum entropy models were used to explore the habitats of both fleas under different climate scenarios to provide the scientific basis for the surveillance and control of flea-borne diseases. We screened climate variables by principal component analysis and Pearson's correlation test and evaluated model performance by ROC curve. ArcMap was used to visualize expressions. Under current climatic conditions, the medium and highly suitable areas for P. simulans are estimated to be 9.16 × 106 km2 and 4.97 × 106 km2, respectively. These regions are predominantly located in South America, along the Mediterranean coast of Europe, the southern part of the African continent, the Middle East, North China, and Australia. For P. gwyni, the medium and highly suitable areas under current climatic conditions are approximately 4.01 × 106 and 2.04 × 106 km2, respectively, with the primary distribution in North China extending to the Himalayas, near the Equator in Africa, and in a few areas of Europe. Under future climate scenarios, in the SSP3-7.0 scenario for the years 2081-2100, the area of high suitability for P. simulans is projected to reach its maximum. Similarly, in the SSP2-4.5 scenario for 2061-2080, the area of high suitability for P. gwyni is expected to reach its maximum. Under global climate change, there is a large range in the potential distribution for both fleas, with an overall upward trend in the area of habitat under future climate scenarios. Governments should develop scientific prevention and control measures to prevent the invasive alien species flea.

5.
J Control Release ; 373: 713-726, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39038544

RESUMEN

Nano-mupirocin is a PEGylated nano-liposomal formulation of the antibiotic mupirocin, undergoing evaluation for treating infectious diseases and intratumor bacteria. Intratumoral microbiota play an important role in the regulation of tumor progression and therapeutic efficacy. However, antibiotic use to target intratumoral bacteria should be performed in a way that will not affect the gut microbiota, found to enable the efficacy of cancer treatments. Nano-mupirocin may offer such a selective treatment. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. In-depth characterization of this novel formulation was performed, and the main findings include: (i). the pharmacokinetic analysis of mupirocin administered as Nano-mupirocin vs mupirocin lithium (free drug) demonstrated that most of the Nano-mupirocin in plasma is liposome associated; (ii). microbiome analysis of rat feces showed no significant short-term difference between Nano-mupirocin, mupirocin lithium and controls; (iii). Nano-mupirocin was active against intratumoral F. nucleatum, a tumor promoting bacteria that accumulates in tumors of the AT3 mice model of breast cancer. These data suggest the ability of Nano-mupirocin to target tumor residing and promoting bacteria.

6.
China CDC Wkly ; 6(23): 547-552, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38933660

RESUMEN

Introduction: Plague is a significant global infectious disease, its spread is linked to host and flea populations. Meteorological conditions can impact flea populations and host densities, hence influencing plague outbreaks. Investigating the connection between meteorological factors, flea populations, and rodent densities in Inner Mongolia's natural plague foci can aid in predicting and managing plague outbreaks. Methods: Monthly data on flea index, rodent density, meteorological factors, and normalized difference vegetation index (NDVI) were collected for the study area. Generalized additive modeling (GAM) was used to analyze the non-linear and lag effects of meteorological factors on flea index and rodent density. Structural equation modeling (SEM) was employed to investigate the relationships among meteorological factors, NDVI, flea index, and rodent density. Results: GAM analysis revealed that temperature, precipitation, relative humidity, and NDVI had significant linear, non-linear, and time-lagged impacts on the density of Mongolian gerbils and the flea index. SEM analysis indicated that meteorological factors could directly influence the density and flea index of Mongolian gerbils, or indirectly impact NDVI, subsequently influencing gerbil density and the flea index. Conclusions: Meteorological factors primarily influence gerbil density and flea index indirectly by affecting NDVI and the relationship between flea index and gerbil density. This study offers additional support for the significance of meteorological factors and NDVI in influencing the vector-rodent system, offering valuable insights for predicting and managing plague outbreaks.

7.
Vaccines (Basel) ; 12(6)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38932299

RESUMEN

Hand, foot, and mouth disease (HFMD) is a contagious viral infection predominantly affecting infants and young children, caused by multiple enteroviruses, including Enterovirus 71 (EV71), Coxsackievirus A16 (CA16), Coxsackievirus A10 (CA10), and Coxsackievirus A6 (CA6). The high pathogenicity of HFMD has garnered significant attention. Currently, there is no specific treatment or broad-spectrum preventive measure available for HFMD, and existing monovalent vaccines have limited impact on the overall incidence or prevalence of the disease. Consequently, with the emergence of new viral strains driven by vaccine pressure, there is an urgent need to develop strategies for the rapid response and control of new outbreaks. In this study, we demonstrated the broad protective effect of maternal antibodies against three types of HFMD by immunizing mother mice with a trivalent inactivated vaccine targeting EV71, CA16, and CA10, using a neonatal mouse challenge model. Based on the feasibility of maternal antibodies as a form of passive immunization to prevent HFMD, we prepared a multivalent antiviral milk by immunizing dairy cows with the trivalent inactivated vaccine to target multiple HFMD viruses. In the neonatal mouse challenge model, this immunized milk exhibited extensive passive protection against oral infections caused by the three HFMD viruses. Compared to vaccines, this strategy may offer a rapid and broadly applicable approach to providing passive immunity for the prevention of HFMD, particularly in response to the swift emergence and spread of new variants.

8.
J Affect Disord ; 358: 105-112, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38703902

RESUMEN

BACKGROUND: The association between magnesium status and sleep quality is unclear. The aim of this study was to determine the relationship between renal reabsorption-related magnesium depletion score (MDS) and sleep quality. METHODS: This study was conducted through a cross-sectional survey of adults aged ≥20 years who participated in NHANES 2005-2014. We used weighted logistic regression to examine the association between MDS and sleep quality and performed trend tests to analyze for the presence of a dose-response relationship. Subgroup analyses were performed based on various sleep outcomes and covariates. RESULTS: A total of 20,585 participants were included in the study, with a mean age of 48.8 years and 50.7 % female. After adjusting for all covariates, we found a graded dose-response relationship between MDS and sleep trouble as well as sleep disorder. Further analyses revealed a significant positive association between MDS and sleep apnea (OR = 3.01; 95 % CI 1.37-6.62), but no association with restless legs, insomnia or insufficient sleep. In addition, subgroup analyses revealed that middle-aged, male, obese, low magnesium intake, and depressed patients were more prone to sleep trouble and sleep disorder; interestingly, MDS was positively associated with excessive sleep in subjects ≥60 years and without depression. CONCLUSIONS: Our study found a significant association between MDS and sleep quality, particularly sleep apnea, but adequate magnesium intake may be beneficial in mitigating this association. MDS may be associated with excessive sleep in older adults, but not with insufficient sleep or insomnia.


Asunto(s)
Deficiencia de Magnesio , Calidad del Sueño , Trastornos del Sueño-Vigilia , Humanos , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Deficiencia de Magnesio/epidemiología , Adulto , Trastornos del Sueño-Vigilia/epidemiología , Magnesio/sangre , Encuestas Nutricionales , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Anciano , Adulto Joven , Síndromes de la Apnea del Sueño/epidemiología
9.
Animal Model Exp Med ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38747004

RESUMEN

BACKGROUND: Hand, foot and mouth disease (HFMD) is a common infectious disease caused by viral infection by a variety of enteroviruses, with coxsackievirus A 10 (CA10) having become more prevalent in recent years. METHODS: In this study, models of CA10 infection were established in 7-day-old Institute of Cancer Research (ICR) mice by intraperitoneal injection to analyze the pathogenicity of the virus. RNA sequencing analysis was used to screen the differentially expressed genes (DEGs) after CA10 infection. Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections were also compared with CA10. RESULTS: After CA10 virus infection, the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection. We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle. The RNA-sequencing analysis showed that the DEGs in blood, muscle, thymus and spleen showed heterogeneity after CA10 infection and the most up-regulated DEGs in muscle were enriched in immune-related pathways. Compared with CA16 and EV71 infection, CA10 may have an inhibitory effect on T helper (Th) cell differentiation and cell growth. Additionally, the common DEGs in the three viruses were most enriched in the immune system response, including the Toll-like receptor pathway and the nucleotide-binding and oligomerization domain (NOD)-like pathway. CONCLUSIONS: Our findings revealed a group of genes that coordinate in response to CA10 infection, which increases our understanding of the pathological mechanism of HFMD.

10.
Commun Biol ; 7(1): 586, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755285

RESUMEN

Bats serve as reservoirs for numerous zoonotic viruses, yet they typically remain asymptomatic owing to their unique immune system. Of particular significance is the MHC-I in bats, which plays crucial role in anti-viral response and exhibits polymorphic amino acid (AA) insertions. This study demonstrated that both 5AA and 3AA insertions enhance the thermal stability of the bat MHC-I complex and enrich the diversity of bound peptides in terms of quantity and length distribution, by stabilizing the 310 helix, a region prone to conformational changes during peptide loading. However, the mismatched insertion could diminish the stability of bat pMHC-I. We proposed that a suitable insertion may help bat MHC-I adapt to high body temperatures during flight while enhancing antiviral responses. Moreover, this site-specific insertions may represent a strategy of evolutionary adaptation of MHC-I molecules to fluctuations in body temperature, as similar insertions have been found in other lower vertebrates.


Asunto(s)
Quirópteros , Antígenos de Histocompatibilidad Clase I , Animales , Antígenos de Histocompatibilidad Clase I/metabolismo , Antígenos de Histocompatibilidad Clase I/química , Antígenos de Histocompatibilidad Clase I/genética , Estabilidad Proteica , Péptidos/química , Péptidos/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Presentación de Antígeno , Mutagénesis Insercional
11.
Animal Model Exp Med ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760905

RESUMEN

BACKGROUND: SARS-CoV-2, first identified in late 2019, has given rise to numerous variants of concern (VOCs), posing a significant threat to human health. The emergence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022. At present, the lethal mouse model for the study of SARS-CoV-2 needs supplementation, and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated. METHODS: Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 prototype and Omicron BA.1, respectively. The pathogenicity of the two strains was evaluated by observing clinical symptoms, viral load and pathology. Complete blood count, immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains. RESULTS: Our findings revealed that Omicron BA.1 exhibited significantly lower virulence compared to the SARS-CoV-2 prototype in the mouse model. Additionally, we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1. We found that the proportion of monocytes increased at first and then decreased. The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar. CONCLUSION: Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1. SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.

12.
Bioresour Bioprocess ; 11(1): 51, 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38763955

RESUMEN

Prediabetes is an important stage in the development of diabetes. It is necessary to find a safe, effective and sustainable way to delay and reverse the progression of prediabetes. Akkermansia muciniphila (A. muciniphila) is one of the key bacteria associated with glucose metabolism. Recent studies mainly focus on the effect of A. muciniphila on obesity and insulin resistance, but there is no research on the effect of A. muciniphila on pancreatic ß-cell function and its mechanism in prediabetes. In this study, we investigated the effects of A. muciniphila on ß-cell function, apoptosis and differentiation, as well as its effects on the gut microbiome, intestinal barrier, metaflammation and the expression of Toll-like receptors (TLRs) in a high-fat diet (HFD)-induced prediabetic rat model. The effect of A. muciniphila was compared with dietary intervention. The results showed both A. muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improve ß-cell secretory function, apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4. Additionally, A. muciniphila can further elevate ß-cell secretion, attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet.

13.
MedComm (2020) ; 5(5): e521, 2024 May.
Artículo en Catalán | MEDLINE | ID: mdl-38660687

RESUMEN

This study systematically analyzed the molecular mechanism and function of nuclear factor kappa B subunit 2 (NFKB2) in colorectal cancer (CRC) to investigate the potential of NFKB2 as a therapeutic target for CRC. Various experimental techniques, including RNA sequencing, proteome chip assays, and small molecule analysis, were used to obtain a deeper understanding of the regulation of NFKB2 in CRC. The results revealed that NFKB2 was upregulated in a significant proportion of patients with advanced hepatic metastasis of CRC. NFKB2 played an important role in promoting tumor growth through CD8+ T-cell exhaustion. Moreover, NFKB2 directly interacted with signal transducer and activator of transcription 2 (STAT2), leading to increased phosphorylation of STAT2 and the upregulation of programmed death ligand 1 (PD-L1). Applying a small molecule inhibitor of NFKB2 (Rg5) led to a reduction in PD-L1 expression and improved response to programmed death-1 blockade-based immunotherapy. In conclusion, the facilitated NFKB2-STAT2/PD-L1 axis may suppress immune surveillance in CRC and targeting NFKB2 may enhance the efficacy of immunotherapeutic strategies. Our results provide novel insights into the molecular mechanisms underlying the contribution of NFKB2 in CRC immune escape.

14.
J Med Chem ; 67(4): 2884-2906, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38349664

RESUMEN

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has emerged as a novel and promising therapeutic target for the treatment of lymphomas and autoimmune diseases. Herein, we reported a new class of MALT1 inhibitors featuring a novel "2-thioxo-2,3-dihydrothiazolo[4,5-d]pyrimidin-7(6H)-one" scaffold developed by structure-based drug design. Structure-activity relationship studies finally led to the discovery of MALT1 inhibitor 10m, which covalently and potently inhibited MALT1 protease with the IC50 value of 1.7 µM. 10m demonstrated potent and selective antiproliferative activity against ABC-DLBCL and powerful ability to induce HBL1 apoptosis. 10m also effectively downregulated the activities of MALT1 and its downstream signal pathways. Furthermore, 10m induced upregulation of mTOR and PI3K-Akt signals and exhibited a synergistic antitumor effect with Rapamycin in HBL1 cells. More importantly, 10m remarkably suppressed the tumor growth both in the implanted HBL1 and TMD8 xenograft models. Collectively, this work provides valuable MALT1 inhibitors with a distinct core structure.


Asunto(s)
Caspasas , Linfoma de Células B Grandes Difuso , Humanos , Caspasas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Línea Celular Tumoral , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Transducción de Señal , FN-kappa B/metabolismo
15.
J Virol ; 98(2): e0135823, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38226810

RESUMEN

Hand, foot, and mouth disease (HFMD) is caused by more than 20 pathogenic enteroviruses belonging to the Picornaviridae family and Enterovirus genus. Since the introduction of the enterovirus-71 (EV71) vaccine in 2016, the number of HFMD cases caused by EV71 has decreased. However, cases of infections caused by other enteroviruses, such as coxsackievirus A6 (CA6) and coxsackievirus A10, have been increasing accordingly. In this study, we used a clinical isolate of CA6 to establish an intragastric infection mouse model using 7-day-old mice to mimic the natural transmission route, by which we investigated the differential gene expression profiles associated with virus infection and pathogenicity. After intragastric infection, mice exhibited hind limb paralysis symptoms and weight loss, similar to those reported for EV71 infection in mice. The skeletal muscle was identified as the main site of virus replication, with a peak viral load reaching 2.31 × 107 copies/mg at 5 dpi and increased infiltration of inflammatory cells. RNA sequencing analysis identified differentially expressed genes (DEGs) after CA6 infection. DEGs in the blood, muscle, brain, spleen, and thymus were predominantly enriched in immune system responses, including pathways such as Toll-like receptor signaling and PI3K-Akt signaling. Our study has unveiled the genes involved in the host immune response during CA6 infection, thereby enhancing our comprehension of the pathological mechanism of HFMD.IMPORTANCEThis study holds great significance for the field of hand, foot, and mouth disease (HFMD). It not only delves into the disease's etiology, transmission pathways, and severe complications but also establishes a novel mouse model that mimics the natural coxsackievirus A6 infection process, providing a pivotal platform to delve deeper into virus replication and pathogenic mechanisms. Additionally, utilizing RNA-seq technology, it unveils the dynamic gene expression changes during infection, offering valuable leads for identifying novel therapeutic drug targets. This research has the potential to enhance our understanding of HFMD, offering fresh perspectives for disease prevention and treatment and positively impacting children's health worldwide.


Asunto(s)
Infecciones por Enterovirus , Enterovirus , Enfermedad de Boca, Mano y Pie , Animales , Niño , Humanos , Ratones , Anticuerpos Antivirales , Modelos Animales de Enfermedad , Enterovirus/patogenicidad , Enterovirus/fisiología , Enterovirus Humano A , Infecciones por Enterovirus/patología , Infecciones por Enterovirus/virología , Expresión Génica , Enfermedad de Boca, Mano y Pie/genética , Fosfatidilinositol 3-Quinasas , Virulencia
16.
J Innate Immun ; 16(1): 80-95, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38224674

RESUMEN

BACKGROUND: Neutrophils are the first line of defense against pathogens. They are divided into multiple subpopulations during development and kill pathogens through various mechanisms. Neutrophils are considered one of the markers of severe COVID-19. SUMMARY: In-depth research has revealed that neutrophil subpopulations have multiple complex functions. Different subsets of neutrophils play an important role in the progression of COVID-19. KEY MESSAGES: In this review, we provide a detailed overview of the developmental processes of neutrophils at different stages and their recruitment and activation after SARS-CoV-2 infection, aiming to elucidate the changes in neutrophil subpopulations, characteristics, and functions after infection and provide a reference for mechanistic research on neutrophil subpopulations in the context of SARS-CoV-2 infection. In addition, we have also summarized research progress on potential targeted drugs for neutrophil immunotherapy, hoping to provide information that aids the development of therapeutic drugs for the clinical treatment of critically ill COVID-19 patients.


Asunto(s)
COVID-19 , Neutrófilos , SARS-CoV-2 , Humanos , COVID-19/inmunología , Neutrófilos/inmunología , SARS-CoV-2/inmunología , Inmunoterapia/métodos , Activación Neutrófila , Animales , Infiltración Neutrófila/inmunología
17.
PLoS Negl Trop Dis ; 18(1): e0011883, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38198451

RESUMEN

Rocky Mountain spotted fever is a tick-borne disease that is highly dangerous but often overlooked by the public. To prevent the spread of the disease, it is important to understand the distribution patterns of its vectors' suitable areas. This study aims to explore the potential global suitability of areas for the vectors of Rocky Mountain spotted fever, including Dermacentor variabilis and Amblyomma cajennense under both historical and future climate scenarios. The study also seeks to investigate the impact of climatic factors on the distribution patterns of these vectors. Data on species distribution were downloaded from the Global Biodiversity Information Facility, Web of Science and PubMed database. The climatic variables were downloaded from WorldClim Global Climate Database. The Maximum Entropy Model was used to evaluate the contribution of monthly precipitation, monthly maximum temperature, monthly minimum temperature, elevation, and nineteen other climatic variables to vector survival, as well as to predict the suitable area for the vectors. We found that D. variabilis is distributed in North America, while A. cajennense is mainly distributed in South America, but all other continents except Antarctica have a suitable distribution. D. variabilis is more likely to survive in temperate regions, and A. cajennense is more likely to survive in tropical zones. D. variabilis is more sensitive to temperature, whereas A. cajennense is sensitive to both temperature and precipitation, and A. cajennense prefers tropical regions with hot and humid characteristics. The high suitable areas of both vectors were almost expanded in the ssp5-8.5 scenario, but not so much in the ssp1-2.6 scenario. Highly suitable areas with vectors survival should be strengthened with additional testing to prevent related diseases from occurring, and other highly suitable areas should be alert for entry and exit monitoring to prevent invasion and colonization of vectors.


Asunto(s)
Fiebre Maculosa de las Montañas Rocosas , Enfermedades por Picaduras de Garrapatas , Humanos , Fiebre Maculosa de las Montañas Rocosas/epidemiología , Cambio Climático , Biodiversidad , América del Norte
18.
J Hazard Mater ; 465: 133095, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38056270

RESUMEN

In recent years, various materials have been used to adsorb and remove perfluoroalkyl compounds from water. However, most of these materials have limited applications due to their high cost, complex synthesis, inadequate selectivity and sensitivity, and, even worse, the possibility of introducing secondary pollution. Here, under mild conditions, we prepared an inexpensive imidazolium chloride and nitrogen-rich polymer (TAGX-Cl) with a high cationic loading rate and a high yield (>82%). The adsorbent exhibits excellent pH tolerance (pH=1-9) and achieves nearly 99.9% removal of nine perfluoroalkyl carboxylic acids (PFCAs) within 120 min. Experimental data and theoretical simulations confirmed that synergistic electrostatic interactions, hydrogen bonds, and P-π interactions control the adsorptive ability of TAGX-Cl. This work provides a practical strategy for PFCAs removal.

19.
IEEE Trans Image Process ; 33: 177-190, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38055358

RESUMEN

Interactive image segmentation (IIS) has been widely used in various fields, such as medicine, industry, etc. However, some core issues, such as pixel imbalance, remain unresolved so far. Different from existing methods based on pre-processing or post-processing, we analyze the cause of pixel imbalance in depth from the two perspectives of pixel number and pixel difficulty. Based on this, a novel and unified Click-pixel Cognition Fusion network with Balanced Cut (CCF-BC) is proposed in this paper. On the one hand, the Click-pixel Cognition Fusion (CCF) module, inspired by the human cognition mechanism, is designed to increase the number of click-related pixels (namely, positive pixels) being correctly segmented, where the click and visual information are fully fused by using a progressive three-tier interaction strategy. On the other hand, a general loss, Balanced Normalized Focal Loss (BNFL), is proposed. Its core is to use a group of control coefficients related to sample gradients and forces the network to pay more attention to positive and hard-to-segment pixels during training. As a result, BNFL always tends to obtain a balanced cut of positive and negative samples in the decision space. Theoretical analysis shows that the commonly used Focal and BCE losses can be regarded as special cases of BNFL. Experiment results of five well-recognized datasets have shown the superiority of the proposed CCF-BC method compared to other state-of-the-art methods. The source code is publicly available at https://github.com/lab206/CCF-BC.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38090866

RESUMEN

Real-time semantic segmentation plays an important role in auto vehicles. However, most real-time small object segmentation methods fail to obtain satisfactory performance on small objects, such as cars and sign symbols, since the large objects usually tend to devote more to the segmentation result. To solve this issue, we propose an efficient and effective architecture, termed small objects segmentation network (SOSNet), to improve the segmentation performance of small objects. The SOSNet works from two perspectives: methodology and data. Specifically, with the former, we propose a dual-branch hierarchical decoder (DBHD) which is viewed as a small-object sensitive segmentation head. The DBHD consists of a top segmentation head that predicts whether the pixels belong to a small object class and a bottom one that estimates the pixel class. In this situation, the latent correlation among small objects can be fully explored. With the latter, we propose a small object example mining (SOEM) algorithm for balancing examples between small objects and large objects automatically. The core idea of the proposed SOEM is that most of the hard examples on small-object classes are reserved for training while most of the easy examples on large-object classes are banned. Experiments on three commonly used datasets show that the proposed SOSNet architecture greatly improves the accuracy compared to the existing real-time semantic segmentation methods while keeping efficiency. The code will be available at https://github.com/StuLiu/SOSNet.

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