RESUMEN

Phototherapy has emerged as a potential treatment strategy for bacteria-infected wounds, but the inadequate bacteria-capturing ability and excessive damage to normal tissues from single phototherapy are huge limitations. To solve the issues, herein we report the design of chitosan-based hydrogel with bacteria capturing and combined photothermal/photodynamic sterilization functions. Such hydrogel is prepared by mixing chitosan (CS) as matrix, protoporphyrin (PpIX) as photosensitizer and polydopamine (PDA) as photothermal agent and then chemically cross-linking CS with glutaraldehyde. The resulting CS-PpIX-PDA hydrogel possesses a porous architecture (average pore porosity = 60.9 %), excellent swelling capabilities (swelling ratio = 1855 %) and rheological property (G' > G″). The hydrogel can effectively produce reactive oxygen species (ROS) under 660 nm light irradiation due to the photodynamic effect of PpIX. Owing to the presence of PDA, the hydrogel displays a photoabsorption range between 600 and 1500 nm and can generate maximal temperature of 60 °C within 10 min under 808 nm laser illumination (0.6 W/cm2) through photothermal effect. Besides, under synergetic illumination of 808/660 nm laser, CS-PpIX-PDA hydrogel can induce the death of 99.9999 % of E. coli and 99.99999 % of S. aureus. Importantly, when coated on the wound site, the hydrogel exhibits a remarkable bacteria-trapping ability due to its porous structure and the presence of amino groups on chitosan. Under the excitation of 660/808 nm, the combined photothermal and photodynamic effects can effectively eradicate bacteria. Simultaneously, the hydrogel also demonstrates anti-inflammatory properties and upregulates Heat Shock Protein 90 (HSP90) expression, thereby promoting collagen deposition and facilitating wound healing. Therefore, the study may provide some new insights into the development of multifunctional hydrogel for photothermal-oxidation sterilization of bacteria-infected wound therapy.

RESUMEN

Yellow dilemma, at which a driver can neither stop nor go safely after the onset of yellow signals, is one of the major crash contributory factors at the signal junctions. Studies have visited the yellow dilemma problem using observation surveys. Factors including road environment, traffic conditions, and driver characteristics that affect the driver behaviours are revealed. However, it is rare that the joint effects of situational and attitudinal factors on the driver behaviours at the yellow dilemma zone are considered. In this study, drivers' propensity to stop after the onset of yellow signals is examined using the driving simulator approach. For instances, the association between driver propensity, socio-demographics, safety perception, traffic signals, and traffic and weather conditions are measured using a binary logit model. Additionally, variations in the effect of influencing factors on driver behaviours are accommodated by adding the interaction terms for driver characteristics, traffic flow characteristics, traffic signals, and weather conditions. Results indicate that weather conditions, traffic volume, position of yellow dilemma in the sequence, driver age and safety perception significantly affect the drivers' propensity to stop after the onset of yellow signals. Furthermore, there are remarkable interactions for the effects of driver gender and location of yellow dilemma.

Asunto(s)

Accidentes de Tránsito , Conducción de Automóvil , Simulación por Computador , Tiempo (Meteorología) , Humanos , Conducción de Automóvil/psicología , Hong Kong , Masculino , Femenino , Adulto , Persona de Mediana Edad , Accidentes de Tránsito/prevención & control , Adulto Joven , Seguridad , Toma de Decisiones , Adolescente , Factores de Edad , Modelos Logísticos , Factores Sexuales , Anciano

RESUMEN

Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.

RESUMEN

Perioperative neurocognitive dysfunction (PND) occurs in elderly individuals undergoing anesthesia and surgery. To explore the potential molecular mechanisms, we performed right-sided cervical exploratory surgery under sevoflurane anesthesia in 18-month-old male Sprague-Dawley rats. Anxiety-depression-like behaviors and learning memory abilities were assessed using the Open Field Test (OFT) and Novel Object Recognition (NOR). Additionally, the hippocampus was collected one day after surgery for inflammatory factor detection, TUNEL staining, and metabolomics analysis. Mendelian randomization (MR) analyses were subsequently conducted to validate the causal relationships by using a series of GWAS datasets related to representative differential metabolites as exposures and cognitive impairment as endpoints. The results indicated that rats exposed to anesthesia and surgery exhibited poorer cognitive performance, significant elevations in hippocampal inflammatory factors such as IL-1ß and TNF-α, and extensive neuronal apoptosis. LC-MS/MS-based untargeted metabolomics identified 19 up-regulated and 32 down-regulated metabolites in the test group, with 6 differential metabolites involved in metabolic pathways enriched according to the KEGG database. ROC analysis revealed a correlation between α-linolenic acid (ALA) and linoleic acid (LA) and the development of PND. Further MR analysis confirmed that ALA was significantly associated with cognitive performance and the risk of depression, while LA was significantly associated with the risk of memory loss. Taken together, our results identified ALA and LA as potentially powerful biomarkers for PND.

Asunto(s)

Biomarcadores , Ácido Linoleico , Análisis de la Aleatorización Mendeliana , Metabolómica , Ratas Sprague-Dawley , Ácido alfa-Linolénico , Masculino , Animales , Metabolómica/métodos , Biomarcadores/sangre , Ratas , Hipocampo/metabolismo , Disfunción Cognitiva/genética , Disfunción Cognitiva/etiología , Trastornos Neurocognitivos/genética , Trastornos Neurocognitivos/etiología , Periodo Perioperatorio

RESUMEN

Oxidative stress has been identified as a major factor in the development and progression of pain and psychiatric disorders, but the underlying biomarkers and molecular signaling pathways remain unclear. This study aims to identify oxidative stress-related biomarkers and signaling pathways in pain-depression comorbidity. Integrated bioinformatics analyses were applied to identify key genes by comparing pain-depression comorbidity-related genes and oxidative stress-related genes. A total of 580 differentially expressed genes and 35 differentially expressed oxidative stress-related genes (DEOSGs) were identified. By using a weighted gene co-expression network analysis and a protein-protein interaction network, 43 key genes and 5 hub genes were screened out, respectively. DEOSGs were enriched in biological processes and signaling pathways related to oxidative stress and inflammation. The five hub genes, RNF24, MGAM, FOS, and TKT, were deemed potential diagnostic and prognostic markers for patients with pain-depression comorbidity. These genes may serve as valuable targets for further research and may aid in the development of early diagnosis, prevention strategies, and pharmacotherapy tools for this particular patient population.

Asunto(s)

Biomarcadores , Comorbilidad , Biología Computacional , Depresión , Redes Reguladoras de Genes , Estrés Oxidativo , Dolor , Mapas de Interacción de Proteínas , Estrés Oxidativo/genética , Humanos , Biología Computacional/métodos , Dolor/genética , Dolor/epidemiología , Mapas de Interacción de Proteínas/genética , Depresión/genética , Depresión/epidemiología , Perfilación de la Expresión Génica , Transducción de Señal/genética

RESUMEN

BACKGROUND: Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat, is a pathologic characteristic of Crohn's disease (CD). In our previously reported cohort, we observed that Achromobacter pulmonis was the most abundant and prevalent bacteria cultivated from creeping fat. METHODS: A whole genomic sequencing and identification of T3SS orthologs of mAT-derived A. pulmonis were used. A functional type III secretion system (T3SS) mediated the pathogenic potential of A. pulmonis in vitro and in mouse colitis model. Furthermore, a T3SS Finder pipeline was introduced to evaluate gut bacterial T3SS orthologs in the feces of CD patients, ulcerative colitis and colorectal cancer patients. FINDINGS: Here, we reveal that mAT-derived A. pulmonis possesses a functional T3SS, aggravates colitis in mice via T3SS, and exhibits T3SS-dependent cytotoxicity via a caspase-independent mechanism in macrophages and epithelial cells, which demonstrated the pathogenic potential of the T3SS-harboring A. pulmonis. Metagenomic analyses demonstrate an increased abundance of Achromobacter in the fecal of Crohn's disease patients compared to healthy controls. A comprehensive comparison of total microbial vT3SS abundance in various intestine diseases demonstrated that the specific enrichment of vT3SS genes was shown in fecal samples of CD, neither ulcerative colitis nor colorectal cancer patients, and ten T3SS gene-based biomarkers for CD were discovered and validated in a newly recruited CD cohort. Furthermore, treatment with exclusive enteral nutrition (EEN), an intervention that improves CD patient symptomatology, was found associated with a significant reduction in the prevalence of T3SS genes in fecal samples. INTERPRETATION: These findings highlight the pathogenic significance of T3SSs in the context of CD and identify specific T3SS genes that could potentially function as biomarkers for diagnosing and monitoring the clinical status of CD patients. FUNDING: This work is supported by the National Key Research and Development Program of China (2020YFA0907800), the China Postdoctoral Science Foundation (2023M744089), the National Natural Science Foundation of China (32000096), the Shenzhen Science and Technology Programs (KQTD20200820145822023, RCIC20231211085944057, and ZDSYS20220606100803007), National Key Clinical Discipline, Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), Qingfeng Scientific Research Fund of the China Crohn's & Colitis Foundation (CCCF) (CCCF-QF-2022B71-1), and the Sixth Affiliated Hospital, Sun Yat-sen University Clinical Research 1010 Program 1010CG(2023)-08. These funding provided well support for this research work, which involved data collection, analysis, interpretation, patient recruitment and so on.

Asunto(s)

Biomarcadores , Enfermedad de Crohn , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Sistemas de Secreción Tipo III , Animales , Ratones , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Humanos , Sistemas de Secreción Tipo III/metabolismo , Sistemas de Secreción Tipo III/genética , Colitis/microbiología , Colitis/metabolismo , Metagenómica/métodos , Heces/microbiología , Femenino , Masculino

RESUMEN

Gut microbiota of centenarians has garnered significant attention in recent years, with most studies concentrating on the analysis of microbial composition. However, there is still limited knowledge regarding the consistent signatures of specific species and their biological functions, as well as the potential causal relationship between gut microbiota and longevity. To address this, we performed the fecal metagenomic analysis of eight longevous populations at the species and functional level, and employed the Mendelian randomization (MR) analysis to infer the causal associations between microbial taxa and longevity-related traits. We observed that several species including Eisenbergiella tayi, Methanobrevibacter smithii, Hungatella hathewayi, and Desulfovibrio fairfieldensis were consistently enriched in the gut microbiota of long-lived individuals compared to younger elderly and young adults across multiple cohorts. Analysis of microbial pathways and enzymes indicated that E. tayi plays a role in the protein N-glycosylation, while M. smithii is involved in the 3-dehydroquinate and chorismate biosynthesis. Furthermore, H. hathewayi makes a distinct contribution to the purine nucleobase degradation I pathway, potentially assisting the elderly in maintaining purine homeostasis. D. fairfieldensis contributes to the menaquinone (vitamin K2) biosynthesis, which may help prevent age-related diseases such as osteoporosis-induced fractures. According to MR results, Hungatella was significantly positively correlated with parental longevity, and Desulfovibrio also exhibited positive associations with lifespan and multiple traits related to parental longevity. Additionally, Alistipes and Akkermansia muciniphila were consistently enriched in the gut microbiota of the three largest cohorts of long-lived individuals, and MR analysis also suggests their potential causal relationships with longevity. Our findings reveal longevity-associated gut microbial signatures, which are informative for understanding the role of microbiota in regulating longevity and aging.

Asunto(s)

Bacterias , Heces , Microbioma Gastrointestinal , Longevidad , Humanos , Anciano de 80 o más Años , Heces/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Femenino , Adulto , Masculino , Anciano , Adulto Joven , Metagenómica , Persona de Mediana Edad , Desulfovibrio/genética , Desulfovibrio/metabolismo

RESUMEN

Diffusion-weighted imaging (DWI) is widely utilized for evaluating uterine diseases. However, the prevalent technique, single-shot echo planar imaging (ssEPI), is hindered by notable image distortion and low spatial resolution. Therefore, optimizing uterine DWI sequences is vital for improving image quality. To investigate the efficacy of multiplexed sensitivity encoding (MUSE) combined with reverse polarity gradient (RPG) in enhancing uterine DWI quality and assessing local invasion in endometrial and cervical cancer, we included 149 patients. Each patient underwent DWI of the uterus using ssEPI, MUSE, and RPG-MUSE techniques. We compared these three sequences regarding image quality, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), geometric distortion rate (GDR), ADC values, accuracy in determining the extent of cancer invasion, and the Area Under the Curve (AUC) for identifying endometrial cancer and benign endometrial lesions using ADC values. The results indicated that RPG-MUSE DWI had less artifacts than MUSE and ssEPI (P < 0.05). Lesions were more apparent in MUSE and RPG-MUSE sequences compared to ssEPI (P < 0.05), with RPG-MUSE providing clearer lesion edges (P < 0.05). Additionally, RPG-MUSE DWI demonstrated higher SNR and CNR than ssEPI and MUSE (P < 0.05), along with a lower GDR (P < 0.05). The ADC values did not show significant differences among the three sequences (P > 0.05). Furthermore, the AUC of the ROC for detecting endometrial cancer and benign endometrial lesions using ADC values showed no significant differences across the sequences (P = 0.7609, 0.7186, and 0.8706, respectively). When combining each DWI sequence with T2WI for FIGO staging, RPG-MUSE and MUSE exhibited better alignment with pathology findings compared to ssEPI (P < 0.05). Overall, RPG-MUSE DWI showed fewer artifacts, higher SNR and CNR, reduced geometric distortion, and clearer lesion visualization compared to ssEPI and MUSE, leading to a more precise assessment of endometrial and cervical cancer invasion extent.

RESUMEN

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we characterized the overall infectomes of companion animals (cats and dogs) and evaluated their potential zoonotic risks. Meta-transcriptomic analyses were performed on 239 samples from cats and dogs collected across China, identifying 24 viral species, 270 bacterial genera, and two fungal genera. Differences in the overall microbiome and infectome composition were compared across different animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). Diversity analyses revealed that viral abundance was generally higher in diseased animals compared to healthy ones, while differences in microbial composition were mainly driven by sampling site, followed by animal species and health status. Disease association analyses validated the pathogenicity of known pathogens and suggested potential pathogenic roles of previously undescribed bacteria and newly discovered viruses. Cross-species transmission analyses identified seven pathogens shared between cats and dogs, such as alphacoronavirus 1, which was detected in both oropharyngeal and rectal swabs albeit with differential pathogenicity. Further analyses showed that some viruses, like alphacoronavirus 1, harbored multiple lineages exhibiting distinct pathogenicity, tissue, or host preferences. Ultimately, a systematic evolutionary screening identified 27 potential zoonotic pathogens in this sample set, with far more bacterial than viral species, implying potential health threats to humans. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, highlighting key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats. IMPORTANCE: This study provides a comprehensive characterization of the entire community of infectious microbes (viruses, bacteria, and fungi) in companion animals like cats and dogs, termed the "infectome." By analyzing hundreds of samples from across China, the researchers identified numerous known and novel pathogens, including 27 potential zoonotic agents that could pose health risks to both animals and humans. Notably, some of these zoonotic pathogens were detected even in apparently healthy pets, highlighting the importance of surveillance. The study also revealed key microbial factors associated with respiratory and gastrointestinal diseases in pets, as well as potential cross-species transmission events between cats and dogs. Overall, this work sheds light on the complex microbial landscapes of companion animals and their potential impacts on animal and human health, underscoring the need for monitoring and management of these infectious agents.

Asunto(s)

Bacterias , Enfermedades de los Gatos , Enfermedades de los Perros , Mascotas , Zoonosis , Animales , Gatos , Perros , Mascotas/virología , Mascotas/microbiología , Humanos , Enfermedades de los Perros/microbiología , Enfermedades de los Perros/virología , Enfermedades de los Perros/transmisión , Zoonosis/microbiología , Zoonosis/virología , Zoonosis/transmisión , Enfermedades de los Gatos/virología , Enfermedades de los Gatos/microbiología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Microbiota/genética , China , Virus/clasificación , Virus/genética , Virus/aislamiento & purificación , Virus/patogenicidad , Hongos/clasificación , Hongos/genética , Hongos/aislamiento & purificación , Hongos/patogenicidad , Perfilación de la Expresión Génica , Transcriptoma

RESUMEN

This study is the first work investigating the distribution of rare earth elements (REEs) in three different edible tissues of the swimming crab (Portunus trituberculatus) collected from seven cities of Shandong Province, China. The total concentrations of REEs ranged from 26.1 to 139 ng/g with an average of 63.0 ng/g. The ratio of light REEs to heavy REEs ranged from 9.78 to 16.6 ng/g with an average of 11.5 ng/g. There was no significant differences in REE levels between the edible tissues of male and female crabs. The content of REEs across different tissues followed a consistent pattern: gonads > body muscle > legs muscle, except for Eu. A significant correlation was observed between REEs in P. trituberculatus and marine sediments in the corresponding sea area, following the principle of "abundance law". A health risk assessment revealed a low health risk of REEs for local adults and children consuming Portunus trituberculatus.

Asunto(s)

Braquiuros , Metales de Tierras Raras , Animales , Metales de Tierras Raras/análisis , China , Medición de Riesgo , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Masculino , Femenino , Humanos , Alimentos Marinos/análisis

RESUMEN

The steady increase in the prevalence of inflammatory bowel disease (IBD) is regarded as a worldwide health issue. Gut microorganisms could modulate host immune and metabolic status and are associated with health effects. Probiotics, Lactobacillus rhamnosus GG (LGG), are beneficial microorganisms that ameliorate disease and exert advantageous effects on intestinal homeostasis. However, the viability of probiotics will suffer from various risk factors in the digestive tract. In this view, we developed a probiotic coating with nanocomposite using tannic acid (TA) and casein phosphopeptide (CPP) through layer-by-layer technology to overcome the challenges after oral administration. LGG showed an improved survival rate in simulated gastrointestinal conditions after coated. The coating (LGG/TA-Mg2+/CPP) had potent reactive oxygen species (ROS) scavenging ability and improved the survival rate of colorectal epithelial cells after H2O2 stimulation. In DSS-induced colitis, administration of LGG/TA-Mg2+/CPP ameliorated intestinal inflammation and reduced the disruption of barrier function. Furthermore, LGG/TA-Mg2+/CPP increased the abundance and diversity of the gut microbiota. In the mouse model of DSS colitis, LGG/TA-Mg2+/CPP can better activate the EGFR/AKT signaling pathway, thereby protecting the epithelial barrier function of the colon epithelium. In conclusion, the probiotic coating with nanocomposite may become a delivery platform for probiotics applied to IBD.

Asunto(s)

Colitis , Microbioma Gastrointestinal , Lacticaseibacillus rhamnosus , Ratones Endogámicos C57BL , Nanocompuestos , Probióticos , Animales , Nanocompuestos/química , Probióticos/farmacología , Probióticos/administración & dosificación , Ratones , Colitis/microbiología , Colitis/inducido químicamente , Colitis/patología , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Taninos/farmacología , Caseínas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sulfato de Dextran , Masculino , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/microbiología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Inflamación/patología , Inflamación/tratamiento farmacológico , Modelos Animales de Enfermedad

RESUMEN

BACKGROUND: Cellular senescence is essential to TME development, progression, and remodeling. Few studies have examined cellular senescence in HCC after TACE. Investigating the relationship between cellular senescence, post-TACE prognosis, the TME, and immune treatment responses is crucial. METHODS: We analyzed the GSE104580 dataset to identify DEGs. A cellular senescence-related signature was developed using LASSO Cox regression in the GSE14520 dataset and validated in the ICGC dataset. High- and low-risk subgroups were compared using GSVA and GSEA. Correlation studies were conducted to explore the relationship between the prognostic model, immune infiltration, immunotherapy response, and drug sensitivity. RESULTS: A cellular senescence-related signature comprising FOXM1, CDK1, CHEK1, and SERPINE1 was created and validated. High-risk patients showed significantly lower OS than low-risk patients. High-risk patients had carcinogenetic pathways activated, immunosuppressive cells infiltrated, and immunomodulatory genes overexpressed. They also showed higher sensitivity to EPZ004777_1237 and MK-2206_1053 and potential benefits from GSK-3 inhibitor IX, nortriptyline, lestaurtinib, and JNK-9L. CONCLUSIONS: This study constructed a cellular senescence-related signature that could be used to predict HCC patients' responses to and prognosis after TACE treatment, aiding in the development of personalized treatment plans.

RESUMEN

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%-80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c-Myc, further promoting the stability of c-Myc via deacetylation-mediated inhibition of K48-linked ubiquitylation. Stably expressed c-Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p-AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD-L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c-Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

RESUMEN

OBJECTIVE: Whether physical activity could reduce the risk of atrial fibrillation (AF) remains unclear. This study was to investigate the relationship of leisure-time physical activity (LTPA) with AF incidence among Chinese older adults. METHODS: A total of 3253 participants aged ≥60 years from the Guangzhou Heart Study were successfully followed between March 2018 and September 2019. LTPA was assessed using a modified Global Physical Activity Questionnaire. AF was ascertained by 12-lead electrocardiograms, 24-hour single-lead Holter and clinical examination. The Cox proportional hazards model was used to the estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for confounders, and the population-attributable fraction (PAF) was estimated. RESULTS: A total of 76 (2.34%) new-onset cases of AF were identified during a median of 31.13 months of follow-up. After adjustment for confounders, subjects who had LTPA at least 10.0 metabolic equivalent (MET)-hours/week had a 55% lower risk of developing AF (HR: 0.45, 95%CI: 0.25-0.81), and at least 20 MET-hours/week reduced the risk by 45% (HR: 0.55, 95%CI: 0.34-0.92). At least 11% (PAF: 11%, 95%CI: 0%-20%) or 14% (PAF: 14%, 95%CI: 0%-26%) of AF cases could be avoided, respectively, if the subjects do LTPA at least 10 MET-hours/week or 20 MET-hours/week. A significant exposure-response trend was also observed between LTPA and AF risk (Plinear-trend = 0.002). For a specific LTPA, doing housework was associated with a 43% reduced risk, while engaging in ball games was associated with an increased risk. CONCLUSION: This prospective cohort study indicated that a higher LTPA volume was associated with a lower AF risk in Chinese older adults.

Asunto(s)

Fibrilación Atrial , Ejercicio Físico , Actividades Recreativas , Humanos , Fibrilación Atrial/epidemiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/prevención & control , Masculino , Femenino , Anciano , Estudios Prospectivos , Incidencia , Persona de Mediana Edad , China/epidemiología , Factores de Riesgo

RESUMEN

Breast cancer remains a significant global health challenge, and its mechanisms of progression and metastasis are still not fully understood. In this study, analysis of TCGA and GEO datasets revealed a significant increase in CCT2 expression in breast cancer tissues, which was associated with poor prognosis in breast cancer patients. Functional analysis revealed that CCT2 promoted breast cancer growth and metastasis through activation of the JAK2/STAT3 signaling pathway. Additionally, the E3 ubiquitin ligase Trim21 facilitated CCT2 ubiquitination and degradation, significantly reversing the protumor effects of CCT2. Most interestingly, we discovered that exosomal CCT2 derived from breast cancer cells suppressed the activation and proinflammatory cytokine secretion of CD4+ T cell. Mechanistically, exosomal CCT2 constrained Ca2+-NFAT1 signaling, thereby reducing CD40L expression on CD4+ T cell. These findings highlight CCT2 upregulation as a potential driver of breast cancer progression and immune evasion. Our study provides new insights into the molecular mechanisms underlying breast cancer progression, suggesting that CCT2 is a promising therapeutic target and prognostic predictor for breast cancer.

Asunto(s)

Neoplasias de la Mama , Linfocitos T CD4-Positivos , Progresión de la Enfermedad , Ribonucleoproteínas , Ubiquitinación , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/inmunología , Animales , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Ratones , Línea Celular Tumoral , Transducción de Señal , Activación de Linfocitos , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Proliferación Celular , Ratones Endogámicos BALB C , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Pronóstico

RESUMEN

[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test-retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility.

Asunto(s)

Encéfalo , Radioisótopos de Carbono , Fentanilo , Tomografía de Emisión de Positrones , Receptores Opioides mu , Animales , Receptores Opioides mu/metabolismo , Fentanilo/análogos & derivados , Fentanilo/metabolismo , Fentanilo/farmacología , Ratas , Tomografía de Emisión de Positrones/métodos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Masculino , Ratas Sprague-Dawley , Radiofármacos/farmacocinética

RESUMEN

Wound infections pose a major healthcare issue, affecting the well-being of millions of patients worldwide. Effective intervention and on-site detection are important in wound management. However, current approaches are hindered by time-consuming analysis and a lack of technology for real-time monitoring and prompt therapy delivery. In this study, a smart wound patch system (SWPS) designed for wireless closed-loop and in-situ wound management is presented. The SWPS integrates a microfluidic structure, an organic electrochemical transistor (OECT) based sensor, an electrical stimulation module, and a miniaturized flexible printed circuit board (FPCB). The OECT incorporates a bacteria-responsive DNA hydrogel-coated gate for continuous monitoring of bacterial virulence at wound sites. Real-time detection of OECT readings and on-demand delivery of electrical cues to accelerate wound healing is facilitated by a mobile phone application linked with an FPCB containing low-power electronics equipped with parallel sensing and stimulation circuitry. In this proof-of-concept study, the functionality of the SWPS is validated and its application both in vitro and in vivo is demonstrated. This proposed system expands the arsenal of tools available for effective wound management and enables personalized treatment.

Asunto(s)

Tecnología Inalámbrica , Cicatrización de Heridas , Tecnología Inalámbrica/instrumentación , Animales , Infección de Heridas/terapia , Diseño de Equipo/métodos , Ratones , Modelos Animales de Enfermedad , Humanos

RESUMEN

Approximately one-third of postoperative patients are troubled by postoperative pain. Effective treatments are still lacking. The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF)-VGF (non-acronymic) in dorsal root ganglia (DRG) in postoperative pain. Pain behaviors were assessed through measurements of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). Transcriptome analysis was conducted to identify potential targets associated with postoperative pain. Western blotting, immunofluorescence, and ELISA were employed to further detect macrophage activation as well as the expression of BDNF, VGF, TNF-α, IL-1ß, and IL-6. Results showed that plantar incision induced both mechanical and thermal hyperalgesia. Transcriptome analysis suggested that plantar incision caused upregulation of BDNF and VGF. The expressions of BDNF and VGF were upregulated in isolectin B4-positive (IB4+) and calcitonin gene-related peptide-positive (CGRP+) neurons, rather than neurofilament 200-positive (NF200+) neurons. The activation of BDNF-VGF pathway upregulated expression of IL-6, TNF-α, and IL-1ß and promoted the activation of macrophages. In conclusion, BDNF-VGF pathway aggravates acute postoperative pain by promoting macrophage activation and pro-inflammatory cytokine production, which may provide a new target for the treatment of postoperative pain.

RESUMEN

The integration of two-dimensional Ti3C2Tx nanosheets and other materials offers broader application options in the antibacterial field. Ti3C2Tx-based composites demonstrate synergistic physical, chemical, and photodynamic antibacterial activity. In this review, we aim to explore the potential of Ti3C2Tx-based composites in the fabrication of an antibiotic-free antibacterial agent with a focus on their systematic classification, manufacturing technology, and application potential. We investigate various components of Ti3C2Tx-based composites, such as metals, metal oxides, metal sulfides, organic frameworks, photosensitizers, etc. We also summarize the fabrication techniques used for preparing Ti3C2Tx-based composites, including solution mixing, chemical synthesis, layer-by-layer self-assembly, electrostatic assembly, and three-dimensional (3D) printing. The most recent developments in antibacterial application are also thoroughly discussed, with special attention to the medical, water treatment, food preservation, flexible textile, and industrial sectors. Ultimately, the future directions and opportunities are delineated, underscoring the focus of further research, such as elucidating microscopic mechanisms, achieving a balance between biocompatibility and antibacterial efficiency, and investigating effective, eco-friendly synthesis techniques combined with intelligent technology. A survey of the literature provides a comprehensive overview of the state-of-the-art developments in Ti3C2Tx-based composites and their potential applications in various fields. This comprehensive review covers the variety, preparation methods, and applications of Ti3C2Tx-based composites, drawing upon a total of 171 English-language references. Notably, 155 of these references are from the past five years, indicating significant recent progress and interest in this research area.

Asunto(s)

Antibacterianos , Titanio , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Titanio/química , Titanio/farmacología , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología