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Background: Necrotizing soft-tissue infection (NSTI) is a rare and serious disease with high morbidity and mortality. Standard therapeutic concepts have included urgent surgical intervention, broad-spectrum antibiotic treatment, and intensive care. Hyperbaric oxygen therapy (HBOT) is used as adjuvant therapy in some centers, but its benefits remain controversial. Methods: A retrospective analysis was conducted in which 98 patients with a clinical diagnosis of NSTI were treated with standard treatments plus HBOT. The clinical outcomes were wound healing, performance status, hospital length, complication rate, recurrence rate, morbidity (amputation rate), and mortality. Primary or secondary outcomes were compared between the time interval of HBOT and the clinical outcomes. Results: The average times from diagnosis of NSTI to initial HBO treatment and from initial surgery to initial HBO treatment were both significantly longer in dead patients than in surviving patients (P = 0.031; P = 0.020). These two time intervals were both significantly longer in amputated patients than in preserved patients (P = 0.031; P = 0.037). Conclusions: Using combined treatment with early surgical debridement combined with HBOT, it is possible to reduce hospital stay, intensive care unit stay, number of debridements, improve complete wound healing rate, and lower amputation and mortality rates among patients with NSTI. The early onset of HBOT soon after diagnosis, especially during critical conditions, is proved to be associated with higher survival and preservation rates.
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BACKGROUND: Females represent approximately 70% of the Alzheimer's disease (AD) cases and the literature has proposed a connection between the decreased estrogen levels during menopause and an increased AD risk. Previous investigations have predominantly focused on assessing how hormone therapy (HT) affects the likelihood of AD development and cognitive deterioration. However, as the research framework has shifted toward a biomarker-defined AD and alterations in specific biomarkers could take place years before cognitive decline becomes discernible, it is crucial to examine how HT influences AD biomarkers. The main goal of this study was to evaluate the impact of HT on AD biomarker-informed pathophysiology in both cognitively unimpaired (CU) and cognitively impaired (CI) post-menopausal females across the aging and AD spectrum. METHODS: This cross-sectional study included post-menopausal females without HT history (HT-) and with HT (HT+) at the time of PET imaging assessment from two cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD) cohort, and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent magnetic resonance imaging (MRI), positron emission tomography (PET) and biofluid collection. Voxel-based t-tests were performed to assess the differences in amyloid-ß (Aß) and tau neurofibrillary tangles (NFTs) loads between HT- and HT + females. Linear regression models with interaction terms were also conducted to examine the interactive effects of HT and Aß-PET on regional tau-PET. RESULTS: HT + females demonstrated significantly lower tau-PET standardized uptake value ratio (SUVR) in Braak I-II ROIs (P < 0.05, Hedges' g = 0.73), Braak III-IV ROIs (P < 0.0001, Hedges' g = 0.74) and Braak V-VI ROIs (P < 0.0001, Hedges' g = 0.69) compared to HT- females. HT + females also showed significantly lower CSF p-tau181 (P < 0.001) and plasma p-tau181 (P < 0.0001) concentrations. Additionally, results from multivariate linear regression models indicated that HT interacts with cortical Aß and is associated with lower regional NFT load. CONCLUSIONS: Overall, findings from this observational study suggest that HT is associated with lower tau neuroimaging and fluid biomarkers in postmenopausal females. Due to the close link between tau and cognition, this study highlights the need for large randomized controlled trials designed to systemically study the influences of HT on AD biomarkers and disease progression.
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Enfermedad de Alzheimer , Biomarcadores , Posmenopausia , Proteínas tau , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/sangre , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/sangre , Biomarcadores/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Estudios de Cohortes , Estudios Transversales , Terapia de Reemplazo de Estrógeno , Tomografía de Emisión de Positrones , Proteínas tau/líquido cefalorraquídeo , Proteínas tau/sangreRESUMEN
Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.
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Neoplasias Encefálicas , Glioma , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Transducción de Señal , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Glioma/genética , Glioma/patología , Glioma/metabolismo , Mutación , Proteómica/métodos , Procesamiento Proteico-Postraduccional , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/metabolismo , Fosforilación , Clasificación del Tumor , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismoRESUMEN
The leaf beetle Ophraella communa LeSage (Coleoptera: Chrysomelidae) is an effective biological control agent of the common ragweed. Here, we assembled a chromosome-level genome of the O. communa by combining Illumina, Nanopore, and Hi-C sequencing technologies. The genome size of the final genome assembly is 733.1 Mb, encompassing 17 chromosomes, with an improved contig N50 of 7.05 Mb compared to the original version. Genome annotation reveals 25,873 protein-coding genes, with functional annotations available for 22,084 genes (85.35%). Non-coding sequence annotation identified 204 rRNAs, 626 tRNAs, and 1791 small RNAs. Repetitive elements occupy 414.41 Mb, constituting 57.76% of the genome. This high-quality genome is fundamental for advancing biological control strategies employing O. communa.
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Escarabajos , Genoma de los Insectos , Escarabajos/genética , Animales , Anotación de Secuencia Molecular , Cromosomas de InsectosRESUMEN
Analyzing the phosphoproteome at nanoscale poses a significant challenge, mainly due to the substantial sample loss from nonspecific surface adsorption during the enrichment of low stoichiometric phosphopeptides. Here, we describe a tandem tip-based phosphoproteomics sample preparation method capable of sequential sample cleanup and enrichment without the need for additional sample transfer, thereby minimizing sample loss. Integration of this method to our recently developed SOP (surfactant-assisted one-pot sample preparation) and iBASIL (improved boosting to amplify signal with isobaric labeling) approaches creates a streamlined workflow, enabling sensitive, high-throughput nanoscale phosphoproteomics measurements.
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Fosfopéptidos , Fosfoproteínas , Proteómica , Flujo de Trabajo , Proteómica/métodos , Fosfoproteínas/análisis , Fosfoproteínas/metabolismo , Fosfopéptidos/análisis , Humanos , Espectrometría de Masas en Tándem/métodosRESUMEN
Small extracellular vesicles (sEVs) are cell-released vesicles ranging from 30-150nm in size. They have garnered increasing attention because of their potential for both the diagnosis and treatment of disease. The diversity of sEVs derives from their biological composition and cargo content. Currently, the isolation of sEV subpopulations is primarily based on bio-physical and affinity-based approaches. Since a standardized definition for sEV subpopulations is yet to be fully established, it is important to further investigate the correlation between the biomolecular composition of sEVs and their physical properties. In this study, we employed a platform combining single-vesicle surface-enhanced Raman spectroscopy (SERS) and machine learning to examine individual sEVs isolated by size-exclusion chromatography (SEC). The biomolecular composition of each vesicle examined was reflected by its corresponding SERS spectral features (biomolecular "fingerprints"), with their roots in the composition of their collective Raman-active bonds. Origins of the SERS spectral features were validated through a comparative analysis between SERS and mass spectrometry (MS). SERS fingerprinting of individual vesicles was effective in overcoming the challenges posed by EV population averaging, allowing for the possibility of analyzing the variations in biomolecular composition between the vesicles of similar and/or different sizes. Using this approach, we uncovered that each of the size-based fractions of sEVs contained particles with predominantly similar SERS spectral features. Indeed, more than 84% of the vesicles residing within a particular group were clearly distinguishable from that of the other EV sub-populations, despite some spectral variations within each sub-population. Our results suggest the possibility that size-based EV fractionation methods produce samples where similarly eluted sEVs are correlated with their respective biochemical contents, as reflected by their SERS spectra. Our findings therefore highlight the possibility that the biogenesis and respective biological functionalities of the various sEV fractions may be inherently different.
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Vesículas Extracelulares , Espectrometría Raman , Espectrometría Raman/métodos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Humanos , Cromatografía en Gel/métodos , Aprendizaje Automático , Espectrometría de Masas/métodosRESUMEN
This study tested the hypothesis that ITRI Biofilm prevents adhesion of the chest cavity. Combined extracorporeal shock wave (ECSW) + bone marrow-derived autologous endothelial progenitor cell (EPC) therapy was superior to monotherapy for improving heart function (left ventricular ejection fraction [LVEF]) in minipigs with ischemic cardiomyopathy (IC) induced by an ameroid constrictor applied to the mid-left anterior descending artery. The minipigs (n = 30) were equally designed into group 1 (sham-operated control), group 2 (IC), group 3 (IC + EPCs/by directly implanted into the left ventricular [LV] myocardium; 3 [+]/3[-] ITRI Biofilm), group 4 (IC + ECSW; 3 [+]/[3] - ITRI Biofilm), and group 5 (IC + EPCs-ECSW; 3 [+]/[3] - ITRI Biofilm). EPC/ECSW therapy was administered by day 90, and the animals were euthanized, followed by heart harvesting by day 180. In vitro studies demonstrated that cell viability/angiogenesis/cell migratory abilities/mitochondrial concentrations were upregulated in EPCs treated with ECSW compared with those in EPCs only (all Ps < 0.001). The LVEF was highest in group 1/lowest in group 2/significantly higher in group 5 than in groups 3/4 (all Ps < 0.0001) by day 180, but there was no difference in groups 3/4. The adhesion score was remarkably lower in patients who received ITRI Biofilm treatment than in those who did not (all Ps <0.01). The protein expressions of oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptotic (mitochondrial-Bax/caspase3/PARP)/fibrotic (TGF-ß/Smad3)/DNA/mitochondria-damaged (γ-H2AX/cytosolic-cytochrome-C/p-DRP1), and heart failure/pressure-overload (BNP [brain natriuretic peptide]/ß-MHC [beta myosin heavy chain]) biomarkers displayed a contradictory manner of LVEF among the groups (all Ps < 0.0001). The protein expression of endothelial biomarkers (CD31/vWF)/small-vessel density revealed a similar LVEF within the groups (all Ps < 0.0001). ITRI Biofilm treatment prevented chest cavity adhesion and was superior in restoring IC-related LV dysfunction when combined with EPC/ECSW therapy compared with EPC/ECSW therapy alone.
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Biopelículas , Células Progenitoras Endoteliales , Isquemia Miocárdica , Porcinos Enanos , Animales , Porcinos , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/citología , Isquemia Miocárdica/terapia , Isquemia Miocárdica/complicaciones , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Miocardio/metabolismo , Miocardio/patología , MasculinoRESUMEN
Objective: This study aimed to explore specific biochemical indicators and construct a risk prediction model for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: This study included 234 T2D patients, of whom 166 had DKD, at the First Hospital of Jilin University from January 2021 to July 2022. Clinical characteristics, such as age, gender, and typical hematological parameters, were collected and used for modeling. Five machine learning algorithms [Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF)] were used to identify critical clinical and pathological features and to build a risk prediction model for DKD. Additionally, clinical data from 70 patients (nT2D = 20, nDKD = 50) were collected for external validation from the Third Hospital of Jilin University. Results: The RF algorithm demonstrated the best performance in predicting progression to DKD, identifying five major indicators: estimated glomerular filtration rate (eGFR), glycated albumin (GA), Uric acid, HbA1c, and Zinc (Zn). The prediction model showed sufficient predictive accuracy with area under the curve (AUC) values of 0.960 (95% CI: 0.936-0.984) and 0.9326 (95% CI: 0.8747-0.9885) in the internal validation set and external validation set, respectively. The diagnostic efficacy of the RF model (AUC = 0.960) was significantly higher than each of the five features screened with the highest feature importance in the RF model. Conclusion: The online DKD risk prediction model constructed using the RF algorithm was selected based on its strong performance in the internal validation.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Neuroglía , Proteínas tau , Enfermedad de Alzheimer/metabolismo , Humanos , Proteínas tau/metabolismo , Péptidos beta-Amiloides/metabolismo , Neuroglía/metabolismo , Neuroglía/patología , Sinapsis/metabolismo , Sinapsis/patología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/patologíaRESUMEN
The melon fly, Bactrocera cucurbitae (Coquillett) (Tephritidae: Diptera), is an invasive pest that poses a significant threat to agriculture in Africa and other regions. Flies are known to use their olfactory systems to recognise environmental chemical cues. However, the molecular components of the chemosensory system of B. cucurbitae are poorly characterised. To address this knowledge gap, we have used next-generation sequencing to analyse the antenna transcriptomes of sexually immature B. cucurbitae adults. The results have identified 160 potential chemosensory genes, including 35 odourant-binding proteins (OBPs), one chemosensory protein (CSP), three sensory neuron membrane proteins (SNMPs), 70 odourant receptors (ORs), 30 ionotropic receptors (IRs), and 21 gustatory receptors (GRs). Quantitative real-time polymerase chain reaction quantitative polymerase chain reaction was used to validate the results by assessing the expression profiles of 25 ORs and 15 OBPs. Notably, high expression levels for BcucOBP5/9/10/18/21/23/26 were observed in both the female and male antennae. Furthermore, BcucOROrco/6/7/9/13/15/25/27/28/42/62 exhibited biased expression in the male antennae, whereas BcucOR55 showed biased expression in the female antennae. This comprehensive investigation provides valuable insights into insect olfaction at the molecular level and will, thus, help to facilitate the development of enhanced pest management strategies in the future.
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The progression of PET-based Braak stages correlates with cognitive deterioration in aging and Alzheimer's disease. Here, we investigate the association between PET-based Braak stages and functional impairment and assess whether PET-based Braak staging predicts a longitudinal decline in the performance of activities of daily living. In this cohort study, we evaluated cognitively unimpaired individuals and individuals with mild cognitive impairment or Alzheimer's disease dementia. Participants underwent [18F]MK6240 tau-PET, were assigned a PET-based Braak stage at baseline and were followed for a mean (SD) of 1.97 (0.66) years. Functional performance was evaluated with the Functional Activities Questionnaire, Everyday Cognition and functional Clinical Dementia Rating sum of boxes. Multiple linear regressions assessed the association of PET-based Braak stages with baseline functionality and with the longitudinal rate of change in functional scores, adjusting for age, sex and amyloid-ß load. We employed voxel-based regression models to investigate the association between functionality and tau-PET signal and assessed the voxel overlap with Braak regions of interest. We included 291 individuals (181 cognitively unimpaired, 56 amyloid-ß+ mild cognitive impairment and 54 amyloid-ß+ Alzheimer's disease) aged 70.60 (7.48) years. At baseline, PET-based Braak stages III-IV (ß = 0.43, P = 0.03) and V-VI (ß = 1.20, P < 0.0001) showed associations with poorer Functional Activities Questionnaire scores. Similarly, stages III-IV (ß = 0.43, P = 0.02) and V-VI (ß = 1.15, P < 0.0001) were associated with worse Everyday Cognition scores. Only stages V-VI were associated with higher functional Clinical Dementia Rating sum of boxes (ß = 1.17, P < 0.0001) scores. Increased tau-PET signals in all Braak regions of interest were linked to worse performance in all tools. The voxelwise analysis showed widespread cortical associations between functional impairment and tau-PET and high voxel overlap with Braak regions of interest. Baseline PET-based Braak stages V-VI predicted significant longitudinal functional decline as assessed by the Functional Activities Questionnaire (ß = 1.69, P < 0.0001), the Everyday Cognition (ß = 1.05, P = 0.001) and the functional Clinical Dementia Rating sum of boxes (ß = 1.29, P < 0.0001). Our results suggest that functional impairment increases with the severity of tau accumulation. These findings also indicate that PET-based Braak staging is a good predictor of functional impairment in the Alzheimer's disease continuum. Finally, our study provides evidence for the clinical significance of the PET-based Braak staging framework.
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The fluorescent flexible sensor for point-of-care quantification of clinical anticoagulant drug, Heparin (Hep), is still an urgent need of breakthrough. In this research, a hyperbranched poly(amido amine) (HPA) was decorated with tetraphenylethene (TPE) and Rhodamine B (RhB), constructing a ratiometric fluorescent sensor (TR-HPA) for Hep. When the sensor was exposed to Hep, the TPE units within the probe skeleton would aggregate, resulting in an increasing fluorescent emission at 483 nm. The 580 nm of fluorescence came from RhB enhance, simultaneously, due to the fluorescence resonance energy transfer. As a result, there are two good linear correlation between the fluorescence emission ratio (E483/E580) of TR-HPA and the Hep concentration over a range of 0-1.0 µM, with a low limit of detection of 3.0 nM. Furthermore, we incorporate the TR-HPA probe into a polyvinyl alcohol (PVA) hydrogel matrix to create a flexible fluorescent sensing system platform, denoted as TR-HPA/PVA. This approach offers a straightforward visual detection method by causing a fluorescence color change from pink to blue when trace amounts of Hep are present. The hydrogel-based fluorescent sensor streamlines the detection procedures for Hep in biomedical applications. It shows great potential in rapid and point-of-care human blood clotting condition monitoring, making it suitable for next-generation wearable medical devices.
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Colorantes Fluorescentes , Heparina , Rodaminas , Humanos , Aminas , Espectrometría de Fluorescencia/métodos , HidrogelesRESUMEN
Understanding whether vascular risk factors (VRFs) synergistically potentiate Alzheimer's disease (AD) progression is important in the context of emerging treatments for preclinical AD. In a group of 503 cognitively unimpaired individuals, we tested whether VRF burden interacts with AD pathophysiology to accelerate neurodegeneration and cognitive decline. Baseline VRF burden was calculated considering medical data and AD pathophysiology was assessed based on cerebrospinal fluid (CSF) amyloid-ß1-42 (Aß1-42) and tau phosphorylated at threonine 181 (p-tau181). Neurodegeneration was assessed with plasma neurofilament light (NfL) and global cognition with the modified version of the Preclinical Alzheimer's Cognitive Composite. The mean (SD) age of participants was 72.9 (6.1) years, and 220 (43.7%) were men. Linear mixed-effects models revealed that an elevated VRF burden synergistically interacted with AD pathophysiology to drive longitudinal plasma NfL increase and cognitive decline. Additionally, VRF burden was not associated with CSF Aß1-42 or p-tau181 changes over time. Our results suggest that VRF burden and AD pathophysiology are independent processes; however, they synergistically lead to neurodegeneration and cognitive deterioration. In preclinical stages, the combination of therapies targeting VRFs and AD pathophysiology might potentiate treatment outcomes.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Masculino , Humanos , Anciano , Femenino , Proteínas tau/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Cognición/fisiología , Progresión de la EnfermedadRESUMEN
INTRODUCTION: We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aß) positive participants using plasma biomarkers. METHODS: In this cross-sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [18 F]AZD4694 and tau-PET with [18 F]MK6240 and measured plasma levels of total tau, pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers to predict tau positivity in Aß+ individuals. RESULTS: Highest associations with tau positivity in Aß+ individuals were found for plasma pTau-217 (AUC [CI95% ] = 0.89 [0.82, 0.96]) and NTA-tau (AUC [CI95% ] = 0.88 [0.91, 0.95]). Combining pTau-217 and NTA-tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI95% = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity. DISCUSSION: The potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice. HIGHLIGHTS: We found that in a cohort without pre-selection pTau-181, pTau-217, and NTA-tau showed the highest association with tau PET positivity. We found that in Aß+ individuals pTau-217 and NTA-tau showed the highest association with tau PET positivity. Combining pTau-217 and NTA-tau resulted in the strongest agreement with the tau PET-based classification.
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Enfermedad de Alzheimer , Humanos , Proteínas tau , Estudios Transversales , Péptidos beta-Amiloides , Biomarcadores , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVES: The purposes of this study were to explore trajectories for patterns of postoperative pain intensity during the first year following hip fracture surgery and the relationships between pain trajectory groups, cognitive impairment, and depressive symptoms. DESIGN: A prospective cohort correlational study. SETTING AND PARTICIPANTS: A total of 325 patients aged 60 years or older who had received hip fracture surgery at a 3000-bed medical center in northern Taiwan from September 2012 to March 2020. METHODS: Data were collected before hospital discharge and at 1, 3, 6, and 12 months postdischarge. Pain intensity was measured using a numeric rating scale; cognitive function was measured with the Taiwan version of the Mini-Mental State Examination; and depressive symptoms were measured by the Geriatric Depression Scale-Short Form. Patients with similar postoperative pain trajectories were categorized into groups and compared with group-based trajectory modeling. Cognitive impairment and depressive symptoms associated with each group were identified by logistic regression. RESULTS: Three different pain trajectory groups were identified: drastic decline-minimum pain (47.7%), gentle decline-mild pain (45.5%), and slight decline-moderate pain (6.8%). Patients with cognitive impairment [odds ratio (OR) 11.01, 95% CI 2.99-10.51] and at risk for depression (OR 49.09, 95% CI 10.46-230.30) were more likely to be in the moderate pain group than the minimum pain group. Patients with cognitive impairment (OR 2.07, 95% CI 1.25-3.42) were more likely to be in the mild pain group than the minimum pain group. Patients at risk for depression (OR 9.68, 95% CI 3.16-29.63) were more likely to be in the moderate pain group than the mild pain group. CONCLUSIONS AND IMPLICATIONS: Identifying postoperative pain trajectories can provide insight into the most appropriate pain management for older persons following hip fracture surgery. Attention should focus on assessments for cognitive impairment and risk of depression to prevent persistent postoperative pain. Future studies of older patients with clinically diagnosed cognitive impairment and depression are suggested.
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Disfunción Cognitiva , Fracturas de Cadera , Humanos , Anciano , Anciano de 80 o más Años , Depresión/epidemiología , Estudios Prospectivos , Cuidados Posteriores , Alta del Paciente , Fracturas de Cadera/cirugía , Fracturas de Cadera/psicología , Disfunción Cognitiva/complicaciones , Cognición , Dolor PostoperatorioRESUMEN
BACKGROUND: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) triggered a significant public health challenge. This study explored the prevalence trends and key genetic characteristics of Hv-CRKP in one Shanghai suburbs hospital during 2014-2018. METHODS: During five years, Hv-CRKP strains identified from 2579 CRKP by specific PCR, were subjected to performed short- and long-read sequencing technology; epidemiological characteristics, antimicrobial-resistance genes (ARGs), virulence determinants, detailed plasmid profiles and conjugation efficiency were comprehensively investigated. RESULTS: 155 Hv-CRKP and 31 non-Hv-CRKP strains were sequenced. Hv-CRKP strains exhibited significant resistance to six common antibiotic classes (>92%). ST11 steadily increased and became the most prevalent ST (85.2%), followed by ST15 (8.5%), ST65 (2.6%), ST23 (1.9%), and ST86 (0.6%). ST11-KL64 (65.2%) rapidly increased from 0 in 2014 to 93.9% in 2018. blaKPC-2 was the primary carbapenemase gene (97.4%). Other ARGs switched from aac(3)-IId to aadA2 in aminoglycoside and from sul1 to sul2 in sulfanilamide. The time-dated phylogenetic tree was divided into four independent evolutionary clades. Clade 1 and 3 strains were mostly limited in the ICU, whereas Clade 2 strains were distributed among multiple departments. Compared to ybt14 in ICEKp12 in Clade 1, Clade 3 strains harbored ybt9 in ICEKp3 and blaCTX-M-65. Hv-CRKP infected more wards than non-Hv-CRKP and showed greater transmission capacity. Three plasmids containing crucial carbapenemase genes demonstrated their early transmission across China. CONCLUSION: The Hv-CRKP ST11-KL64 has rapidly replaced ST11-KL47 and emerged as the predominant epidemic subtype in various hospital wards, highlighting the importance of conducting comprehensive early surveillance for Hv-CRKP, especially in respiratory infections.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Humanos , Klebsiella pneumoniae , Filogenia , China/epidemiología , Antibacterianos/farmacología , Hospitales , Genómica , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Carbapenémicos/farmacología , Infecciones por Klebsiella/epidemiologíaRESUMEN
Females are disproportionately affected by dementia due to Alzheimer's disease. Despite a similar amyloid-ß (Aß) load, a higher load of neurofibrillary tangles (NFTs) is seen in females than males. Previous literature has proposed that Aß and phosphorylated-tau (p-tau) synergism accelerates tau tangle formation, yet the effect of biological sex in this process has been overlooked. In this observational study, we examined longitudinal neuroimaging data from the TRIAD and ADNI cohorts from Canada and USA, respectively. We assessed 457 participants across the clinical spectrum of Alzheimer's disease. All participants underwent baseline multimodal imaging assessment, including MRI and PET, with radioligands targeting Aß plaques and tau tangles, respectively. CSF data were also collected. Follow-up imaging assessments were conducted at 1- and 2-year intervals for the TRIAD cohort and 1-, 2- and 4-year intervals for the ADNI cohort. The upstream pathological events contributing to faster tau progression in females were investigated-specifically, whether the contribution of Aß and p-tau synergism to accelerated tau tangle formation is modulated by biological sex. We hypothesized that cortical Aß predisposes tau phosphorylation and tangle accumulation in a sex-specific manner. Findings revealed that Aß-positive females presented higher CSF p-tau181 concentrations compared with Aß-positive males in both the TRIAD (P = 0.04, Cohen's d = 0.51) and ADNI (P = 0.027, Cohen's d = 0.41) cohorts. In addition, Aß-positive females presented faster NFT accumulation compared with their male counterparts (TRIAD: P = 0.026, Cohen's d = 0.52; ADNI: P = 0.049, Cohen's d = 1.14). Finally, the triple interaction between female sex, Aß and CSF p-tau181 was revealed as a significant predictor of accelerated tau accumulation at the 2-year follow-up visit (Braak I: P = 0.0067, t = 2.81; Braak III: P = 0.017, t = 2.45; Braak IV: P = 0.002, t = 3.17; Braak V: P = 0.006, t = 2.88; Braak VI: P = 0.0049, t = 2.93). Overall, we report sex-specific modulation of cortical Aß in tau phosphorylation, consequently facilitating faster NFT progression in female individuals over time. This presents important clinical implications and suggests that early intervention that targets Aß plaques and tau phosphorylation may be a promising therapeutic strategy in females to prevent the further accumulation and spread of tau aggregates.
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Enfermedad de Alzheimer , Humanos , Masculino , Femenino , Enfermedad de Alzheimer/patología , Fosforilación , Encéfalo/patología , Proteínas tau/metabolismo , Péptidos beta-Amiloides/metabolismo , Ovillos Neurofibrilares/patología , Placa Amiloide/patología , Tomografía de Emisión de Positrones , Biomarcadores/metabolismoRESUMEN
Extracellular vesicle (EV) secretion has been observed in many types of both normal and tumor cells. EVs contain a variety of distinctive cargoes, allowing tumor-derived serum proteins in EVs to act as a minimally invasive method for clinical monitoring. We have undertaken a comprehensive study of the protein content of the EVs from several cancer cell lines using direct data-independent analysis. Several thousand proteins were detected, including many classic EV markers such as CD9, CD81, CD63, TSG101, and Syndecan-1, among others. We detected many distinctive cancer-specific proteins, including several known markers used in cancer detection and monitoring. We further studied the protein content of EVs from patient serum for both normal controls and pancreatic cancer and hepatocellular carcinoma. The EVs for these studies have been isolated by various methods for comparison, including ultracentrifugation and CD9 immunoaffinity column. Typically, 500-1000 proteins were identified, where most of them overlapped with the EV proteins identified from the cell lines studied. We were able to identify many of the cell-line EV protein markers in the serum EVs, in addition to the large numbers of proteins specific to pancreatic and HCC cancers.
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Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Humanos , Proteoma/genética , Proteoma/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo , Línea Celular TumoralRESUMEN
The fruit fly Zeugodacus tau (Diptera: Tephritidae) is a major pest of melons and other cucurbits in Southeast Asia. In this study, we used Illumina, Nanopore, and Hi-C sequencing technologies to assemble a reference genome of Z. tau at the chromosomal level. The assembled genome was 421.79 Mb and consisted of six chromosomes (one X-chromosome + five autosomes). The contig N50 was 4.23 Mb. We identified 20,922 protein-coding genes, of which 17,251 (82.45%) were functionally annotated. Additionally, we found 247 rRNAs, 435 tRNAs, 67 small nuclear RNAs, and 829 small RNAs in the genome. Repetitive elements accounted for 55.30 Mb (13.15%) of the genome. This high-quality genome assembly is valuable for evolutionary and genetic studies of Z. tau and its relative species.
Asunto(s)
Genoma de los Insectos , Tephritidae , Animales , Cromosomas , Anotación de Secuencia Molecular , Filogenia , Secuencias Repetitivas de Ácidos Nucleicos , Tephritidae/genéticaRESUMEN
PURPOSE: To investigate the effect of 4 kinds of prosthodontic materials on masticatory and gingival function. METHODS: A total of 167 patients with dental defects who underwent prosthodontic treatment from October 2019 to January 2022 were collected. They were randomly divided into 4 groups with 41 cases in the pure titanium group, 40 cases in the cobalt-chromium alloy group, 43 cases in the nickel-chromium alloy group and 43 cases in the zirconium dioxide group. The curative effect and satisfaction degree after 6 months of treatment in 4 groups were recorded and compared. The masticatory function (chewing efficiency, bite force), gingival function[plaque index(PLI), gingival index(GI) and sulcus bleeding index(SBI)], gingival crevicular fluid inflammation-related indicators[tumor necrosis factor alpha(TNF-α), interleukin-6(IL-6), aspartate aminotransferase(AST) and alkaline phosphatase (alkaline phosphatase, ALP)] before and after treatment were measured and compared in 4 groups. Statistical analysis was performed with SPSS 20.0 software package. RESULTS: There was no significant difference in curative effect in 4 groups(Pï¼0.05). Before and after treatment, there was no significant difference in mastication efficiency and bite force in 4 groups(Pï¼0.05). Before treatment, there was no significant difference in PLI, GI, SBI, gingival crevicular fluid weight, TNF-α, IL-6, AST and ALP in gingival crevicular fluid in 4 groups(Pï¼0.05). Compared with before treatment, PLI, GI and SBI in 4 groups were decreased after treatment (Pï¼0.05), and the decrease was in the order of cobalt-chromium alloy group≈nickel-chromium alloy groupï¼pure titanium groupï¼zirconia dioxide group. Before treatment, there was no significant difference in the weight of gingival crevicular fluid, TNF-α, IL-6, AST and ALP in gingival crevicular fluid in 4 groups(Pï¼0.05). The crevicular fluid weight, TNF-α, IL-6, AST and ALP in gingival crevicular fluid were significantly increased(Pï¼0.05), and the increase was in the order of zirconia groupï¼pure titanium groupï¼cobalt-chromium alloy group≈nickel-chromium alloy group. There was no significant difference in restoration integrity and color satisfaction in 4 groups(Pï¼0.05), but there was significant difference in marginal fitness and sensitivity satisfaction in 4 groups(Pï¼0.05). CONCLUSIONS: Pure titanium, cobalt-chromium alloy, nickel-chromium alloy and zirconium dioxide can be used for the treatment of dentition defects, and they all can obtain satisfactory chewing function. In addition, zirconium dioxide restoration has the effect of improving gingival function and inflammation-related indicators of gingival crevicular fluid with a broader application prospect.