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1.
J Ethnopharmacol ; 336: 118720, 2025 Jan 10.
Article de Anglais | MEDLINE | ID: mdl-39197802

RÉSUMÉ

ETHNOPHARMACOLOGICAL RELEVANCE: Jinye Baidu granules (JYBD) have been used to treat acute respiratory tract infections and demonstrated clinical efficacy for the treatment of emerging or epidemic respiratory viruses such as SARS-CoV-2 and influenza virus. AIM OF THE STUDY: This study is to investigate the antiviral effect of JYBD against influenza A viruses (IAV) in vitro and in vivo and elucidate its underlying mechanism. MATERIALS AND METHODS: Ultra-high-performance liquid chromatography connected with Orbitrap mass spectrometer (UHPLC-Orbitrap MS) was employed to describe the chemical profile of JYBD. The potential pathways and targets involved in JYBD against IAV infection were predicted by network pharmacology. The efficacy and mechanism of JYBD were validated through both in vivo and in vitro experiments. Moreover, combination therapy with JYBD and the classic anti-influenza drugs was also investigated. RESULTS: A total of 126 compounds were identified by UHPLC-Orbitrap MS, of which 9 compounds were unambiguously confirmed with reference standards. JYBD could significantly inhibit the replication of multiple strains of IAV, especially oseltamivir-resistant strains. The results of qRT-PCR and WB demonstrated that JYBD could inhibit the excessive induction of pro-inflammatory cytokines induced by IAV infection and regulate inflammatory response through inhibiting JAK/STAT, NF-κB and MAPK pathways. Moreover, both JYBD monotherapy or in combination with oseltamivir could alleviate IAV-induced severe lung injury in mice. CONCLUSIONS: JYBD could inhibit IAV replication and mitigate virus-induced excessive inflammatory response. Combinations of JYBD and neuraminidase inhibitors conferred synergistic suppression of IAV both in vitro and in vivo. It might provide a scientific basis for clinical applications of JYBD against influenza virus infected diseases.


Sujet(s)
Antiviraux , Médicaments issus de plantes chinoises , Virus de la grippe A , Pharmacologie des réseaux , Infections à Orthomyxoviridae , Antiviraux/pharmacologie , Animaux , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/composition chimique , Virus de la grippe A/effets des médicaments et des substances chimiques , Chiens , Souris , Humains , Infections à Orthomyxoviridae/traitement médicamenteux , Infections à Orthomyxoviridae/virologie , Cellules rénales canines Madin-Darby , Réplication virale/effets des médicaments et des substances chimiques , Cellules A549 , Souris de lignée BALB C , Mâle , Femelle , Chromatographie en phase liquide à haute performance
2.
Eur Radiol ; 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39235653

RÉSUMÉ

OBJECTIVES: To develop an MRI-based score that enables individualized predictions of the survival benefit of wide over narrow resection margins. MATERIALS AND METHODS: This single-center retrospective study (December 2011 to May 2022) included consecutive patients who underwent curative-intent resection for single Barcelona Clinic Liver Cancer (BCLC) 0/A HCC and preoperative contrast-enhanced MRI. In patients with narrow resection margins, preoperative demographic, laboratory, and MRI variables independently associated with early recurrence-free survival (RFS) were identified using Cox regression analyses, which were employed to develop a predictive score (named "MARGIN"). Survival outcomes were compared between wide and narrow resection margins in a propensity-score matched cohort for the score-stratified low- and high-risk groups, respectively. RESULTS: Four hundred nineteen patients (median age, 54 years; 361 men) were included, 282 (67.3%) undergoing narrow resection margins. In patients with narrow resection margins, age, alpha-fetoprotein (AFP) > 400 ng/mL, protein induced by vitamin K absence or antagonist-II (PIVKA-II) > 200 mAU/mL, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS (p values, 0.002-0.04) and formed the MARGIN score with a testing dataset C-index of 0.75 (95% CI: 0.65-0.84). In the matched cohort, wide resection margin was associated with improved early RFS rate for the high-risk group (MARGIN score ≥ - 1.3; 71.1% vs 41.0%; p = 0.02), but not for the low-risk group (MARGIN score < - 1.3; 79.7% vs 76.1%; p = 0.36). CONCLUSION: In patients with single BCLC 0/A HCC, the MARGIN score may serve as promising decision-making to indicate the need for wide resection margins. CLINICAL RELEVANCE STATEMENT: The MARGIN score has the potential to identify patients who would benefit more from wide resection margins than narrow resection margins, improving the postoperative survival of patients with single BCLC 0/A hepatocellular carcinoma (HCC). KEY POINTS: Age, AFP, PIVKA-II, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS and formed the MARGIN score. The MARGIN score achieved a testing dataset C-index of 0.75. Wide resection margins were associated with improved early RFS for the high-risk group, but not for the low-risk group.

3.
Health Data Sci ; 4: 0127, 2024.
Article de Anglais | MEDLINE | ID: mdl-39247070

RÉSUMÉ

Background: The COVID-19 pandemic has caused a disproportionate impact on the sexual and gender-diverse (SGD) community. Compared with non-SGD populations, their social relations and health status are more vulnerable, whereas public health data regarding SGD are scarce. Methods: To analyze the concerns and health status of SGD individuals, this cohort study leveraged 471,371,477 tweets from 251,455 SGD and 22,644,411 non-SGD users, spanning from 2020 February 1 to 2022 April 30. The outcome measures comprised the distribution and dynamics of COVID-related topics, attitudes toward vaccines, and the prevalence of symptoms. Results: Topic analysis revealed that SGD users engaged more frequently in discussions related to "friends and family" (20.5% vs. 13.1%, P < 0.001) and "wear masks" (10.1% vs. 8.3%, P < 0.001) compared to non-SGD users. Additionally, SGD users exhibited a marked higher proportion of positive sentiment in tweets about vaccines, including Moderna, Pfizer, AstraZeneca, and Johnson & Johnson. Among 102,464 users who self-reported COVID-19 diagnoses, SGD users disclosed significantly higher frequencies of mentioning 61 out of 69 COVID-related symptoms than non-SGD users, encompassing both physical and mental health challenges. Conclusion: The results provide insights into an understanding of the unique needs and experiences of the SGD community during the pandemic, emphasizing the value of social media data in epidemiological and public health research.

4.
Plast Reconstr Surg ; 2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39250351

RÉSUMÉ

OBJECTIVES: The purpose of this study was to investigate the clinical effect of treating axillary osmidrosis by trimming the apocrine glands under direct vision after blunt dissection of the axillary flap through double mini-incisions on both sides of the axilla to prevent postoperative hematoma. METHODS: The clinical data of 108 patients with axillary osmidrosis were retrospectively analyzed. Treatment involved blunt dissection of the axillary flap through double mini-incisions and trimming of the apocrine glands under direct vision. The surgical duration, hematoma incidence, flap necrosis rate, incision healing rate, incision VSS score, comfort level, axillary odor cure rate, and satisfaction rating were all statistically analyzed. RESULTS: The average surgical duration was 72.45±5.71 min. The cure rate of axillary osmidrosis was 100%. Postoperative complications, including delayed incision healing 12 days after surgery (1 patient), a small hematoma (2 patients), and local flap necrosis (1 patient), were minor. No infection, malodor, or recurrence was observed. The VAS score for patient comfort was 8.53±0.89, the VAS score for patient satisfaction was 8.87±0.98, and the VSS score for the incision was 0.84±0.99. CONCLUSION: This retrospective study demonstrated that the trimming of apocrine glands after blunt dissection of the axillary flap through double mini-incisions on both sides of the axilla effectively controlled bleeding. This approach significantly reduces the complication rate of axillary osmidrosis surgery and ensures the complete trimming of apocrine glands, eradicating axillary odor and maintaining a good appearance.

5.
J Sci Food Agric ; 2024 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-39253993

RÉSUMÉ

BACKGROUND: Bacillus inaquosorum strains is widely recognized for their plant-growth-promoting and biocontrol capabilities, yet their roles in protease production remain unclear. The present study aimed to comprehensively assess the protease-producing performance of B. inaquosorum strain E1-8, at the same time as exploring the novel application of agricultural Bacillus proteases in the preparation of protein hydrolysates for fresh-cut fruits preservation. RESULTS: First, genomic sequencing revealed the diversity of E1-8 proteases, indicating 15 putative extracellular proteases. Subsequently, the fermentation conditions for E1-8 protease production were optimized, with sweet potato powder and soybean meal identified as the most suitable carbon and nitrogen sources, respectively, resulting in a maximum protease activity of 321.48 U mL-1. Upon culturing the strain under these optimized conditions, only an S8 family serine protease and an M48 family metalloprotease were revealed by secretomic analysis and protease inhibitor assays. Additionally, the optimal protease conditions for generating protein hydrolysates from soy, pea, fish and porcine proteins were determined. The molecular weight of the hydrolysates primarily ranged from 2000 to 180 Da, with a total of 17 amino acids identified. The application of these hydrolysates demonstrated a 2,2-diphenyl-1-picrylhydrazyl (i.e. DPPH) scavenging activity ranging from 58.64% to 84.12%, significantly reducing of the melting peaks and the freezing points. Furthermore, the browning index of apple slices stored at 4 °C decreased by 14.81% to 22.15% on the second day, and similar effects were observed in fresh-cut banana stored at 4 °C for 7 days. CONCLUSION: The protein hydrolysates obtained exhibit remarkable antioxidant, antifreeze and anti-browning properties for fresh-cut fruits. © 2024 Society of Chemical Industry.

6.
Cancer Med ; 13(17): e7150, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39246263

RÉSUMÉ

BACKGROUND: Leukemia is the tenth most common cause of cancer death worldwide and one of the most important causes of disability. To understand the current status and changing trends of the disease burden of leukemia at the global, regional, and national levels, and to provide a scientific basis for the development of leukemia prevention and treatment strategies. METHODS: Based on open data from the Global Burden of Disease Study 2019 (GBD 2019), R software was used to calculate estimated annual percentage changes to estimate trends in the age-standardized incidence (ASIR) and the age-standardized disability-adjusted life years (DALY) rate due to leukemia and its major subtypes from 1990 to 2019. RESULTS: In 2019, globally, the number of incidences and DALYs of leukemia were 643.6 × 103 (587.0 × 103, 699.7 × 103) and 11,657.5 × 103 (10529.1 × 103, 12700.7 × 103), respectively. The ASIR (estimated annual percentage change (EAPC) = -0.37, 95%UI -0.46 to -0.28) and the age-standardized DALY rate (EAPC = -1.72, 95%UI -1.80 to -1.65) of leukemia showed a decreasing trend from 1990 to 2019. The APC model analysis showed that the age effect of leukemia risk was a "U"-shaped distribution of relative risk (RR) with increasing age from 1990 to 2019, globally. The time effect was an increase in incidence rate with increasing years but a decrease in DALY rate with increasing years. The cohort effects of both incidence and DALY rates tended to increase and then decrease with the development of the birth cohort. In 1990 and 2019, smoking, high body-mass index, occupational exposure to benzene, and occupational exposure to formaldehyde were risk factors for DALY in leukemia, especially in areas with high SDI. CONCLUSIONS: From 1990 to 2019, the disease burden of leukemia showed a decreasing trend, but it is worth noting that its overall severity is still very high. The disease burden of leukemia varies greatly from region to region, and exclusive strategies for the prevention and treatment of leukemia should be developed according to the economic and cultural development of each region.


Sujet(s)
Espérance de vie corrigée de l'incapacité , Charge mondiale de morbidité , Leucémies , Humains , Charge mondiale de morbidité/tendances , Leucémies/épidémiologie , Incidence , Mâle , Femelle , Santé mondiale , Adulte , Adulte d'âge moyen , Sujet âgé , Adolescent , Jeune adulte
7.
J Mater Chem B ; 2024 Sep 11.
Article de Anglais | MEDLINE | ID: mdl-39258387

RÉSUMÉ

High-throughput and label-free protein nanopore-based sensors are extensively used in DNA sequencing, single-protein analysis, molecular sensing and chemical catalysis with single channel recording. These technologies show great potential for identifying various harmful substances linked to public health by addressing the limitations of current portability and the speed of existing techniques. In this review, we provide an overview of the fundamental principles of nanopore sensing, with a focus on chemical modification and genetic engineering strategies aimed at enhancing the detection sensitivity and identification accuracy of protein nanopores. The engineered protein nanopores enable direct sensing, while the introduction of aptamers and substrates enables indirect sensing, translating the physical structure and chemical properties of analytes into readable signals. These scientific discoveries and engineering efforts have provided new prospects for detecting and monitoring trace hazardous substances.

8.
Mycoses ; 67(9): e13785, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39245647

RÉSUMÉ

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.


Sujet(s)
Antifongiques , Consensus , Résistance des champignons aux médicaments , Teigne , Humains , Antifongiques/usage thérapeutique , Antifongiques/pharmacologie , Arthrodermataceae/effets des médicaments et des substances chimiques , Chine , Teigne/traitement médicamenteux , Teigne/microbiologie , Teigne/diagnostic , Trichophyton/effets des médicaments et des substances chimiques , Trichophyton/isolement et purification
9.
Front Cardiovasc Med ; 11: 1423836, 2024.
Article de Anglais | MEDLINE | ID: mdl-39228665

RÉSUMÉ

Background: Contrast-induced nephropathy (CIN) can lead to serious complications following percutaneous coronary intervention (PCI). Urine N-Acetyl-ß-D-glucosaminidase (uNAG) and serum homocysteine (sHCY) are both potential predictors for CIN detection, but their combination has not been explored. We aimed to combine uNAG and sHCY as predictors for the early detection of CIN and for prognosis prediction in patients after PCI. Methods: A total of 232 consecutive patients who underwent PCI at a university hospital were recruited for this study. According to the European Society of Urology and Reproduction (ESUR) criterion, CIN is defined as an elevation of serum creatinine (sCr) by ≥25% or ≥0.5 mg/dl from baseline within 48 h. We assessed the use of individual biomarkers (uNAG and sHCY) measured around PCI and their combinations for CIN detection and prognosis prediction. Receiver operating characteristic curves (ROC) and area under the curve (AUC) were used to evaluate the predictive efficiency of potential predictors. Results: In total, 54 (23.28%) patients developed CIN. Concentrations of uNAG and sHCY increased significantly in CIN subjects (p < 0.05) than non-CIN. CIN could be predicted by uNAG and sHCY but not by creatinine at an early stage. At pre-PCI, 0, 12, 24, and 48 h after PCI, the AUC-ROC value of uNAG in calculating total CIN was 0.594, 0.603, 0.685, 0.657, and 0.648, respectively. The AUC-ROC value of sHCY in calculating total CIN was 0.685, 0.726, 0.771, 0.755, and 0.821, respectively. The panel of uNAG plus sHCY detected CIN with significantly higher accuracy than either individual biomarker alone and earlier than sCr. For detecting total CIN, this panel yielded AUC-ROCs of 0.693, 0.754, 0.826, 0.796, and 0.844 at pre-PCI, 0, 12, 24, and 48 h after PCI, respectively, which were superior to those of the individual biomarkers. For predicting the incidence of major adverse cardiovascular events (MACE) within 30 days to 12 months, the AUC-ROC values for uNAG and sHCY measured before discharge were 0.637 and 0.826, respectively. The combined panel yielded an AUC-ROC of 0.832. The combined detection did not significantly enhance the predictive capability for MACE in patients with CIN. The CIN group and the non-CIN group showed no significant difference in the Coronary Heart Disease Intensive Care Unit (CCU) stay time, hospital stay time, demand for renal replacement therapy, CCU mortality rate, and in-hospital mortality rate. Conclusions: The uNAG and sHCY panel demonstrated better sensitivity and specificity for predicting the diagnosis and prognosis of CIN in patients after PCI, earlier than sCr. The combination of these biomarkers revealed a significantly superior discriminative performance for CIN detection and prognosis compared to using uNAG or sHCY alone.

10.
Front Oncol ; 14: 1454372, 2024.
Article de Anglais | MEDLINE | ID: mdl-39228980

RÉSUMÉ

Objective: To assess the effectiveness and tolerability of both PD-1 and PD-L1 inhibitors in advanced cervical cancer (CC), focusing on varying PD-L1 levels. Methods: A comprehensive exploration was carried out on EMBASE, PubMed, Cochrane Library databases as well as Web of Science up to May 25, 2024, for studies involving advanced CC patients receiving PD-1/PD-L1 inhibitors. Inclusion criteria were studies reporting objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), as well as median overall survival (OS). Data extraction and quality assessment were performed by two reviewers using the JBI Case Series Critical Appraisal Checklist, followed by a meta-analysis via STATA/MP 16.0. Results: Five eligible studies comprising 223 patients were chosen. ORR and DCR were 42% (95% CI: 17%-66%, P = 0.00) and 70% (95% CI: 22%-117%, P = 0.00), respectively, in the PD-L1 positive patients and were 36% (95% CI: 17%-54%, P = 0.00) and 47% (95% CI: 30%-63%, P = 0.00), respectively, in patients with PD-L1 negativity. For patients exhibiting PD-L1 positivity, median PFS and median OS were 3.98 months (95% CI: 0.80-7.16, P = 0.01) and 11.26 months (95% CI: 3.01-12.58, P = 0.00), respectively. Conclusion: With PD-1/PD-L1 inhibitors, PD-L1 positive CC patients demonstrate superior ORR, DCR, median PFS, and median OS, underscoring PD-L1 as one biomarker for immunotherapy response.

11.
Cerebrovasc Dis ; : 1-9, 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39236681

RÉSUMÉ

INTRODUCTION: The fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4) is a large-scale, multicenter, prospective, randomized, open-label, blinded endpoint assessment trial, initiated in an ambulance in China, aiming at evaluating the effectiveness and safety of pre-hospital blood pressure (BP) lowering in patients with suspected acute stroke and elevated BP. A prespecified process evaluation is intended to explore the implementation of the trial intervention, provide support to interpret the trial outcomes and put forward suggestions to scale up the intervention in broader settings in the future. METHODS: This process evaluation is a mixed-methods design, and follows the Normalization Process Theory (NPT) and the UK Medical Research Council (UK MRC) guidance. Fidelity, reach, acceptability, appropriateness, adoption, sustainability, and relevant contextual factors and mechanisms affecting the implementation of pre-hospital early intensive BP lowering treatment will be analyzed. Semi-structured interviews with ambulance staff, ward and emergency department clinicians, and nurses are undertaken to explore perceptions of the intervention, contextual factors, and potential suggestions for future implementation in practice. Data from observational records, surveys, conventional monitoring data, on-site records, and case report forms will be analyzed to understand background care and context. CONCLUSION: The process evaluation of INTERACT4 will provide insights for the implementation of pre-hospital early intensive BP lowering intervention in different health systems, and help better explain the trial results for further scale up.

12.
AAPS PharmSciTech ; 25(7): 210, 2024 Sep 07.
Article de Anglais | MEDLINE | ID: mdl-39242368

RÉSUMÉ

Torsemide is a long acting pyridine sulfonylurea diuretic. Torsemide hydrochloride is widely used now, there are only a few organic acid salts reported. Cocrystallization with organic acids is an effective way to improve its solubility. Here, we reported maleate and phthalate of torsemide, in which the organic acid lost a proton transferring to the pyridine of torsemide, and torsemide interacted with organic acid through N+ - H⋯O- hydrogen bond to form salts crystal. Surprisingly, maleate showed a clear "spring" pattern in apparent solubility, whereas phthalate had a "spring-parachute" effect. Both crystalline salts kept a higher solubility than torsemide without falling. The "spring-parachute" effect of crystalline salts promoted rapid dissolution of torsemide and kept a high concentration, thereby increasing its bioavailability.


Sujet(s)
Cristallisation , Sels , Solubilité , Torasémide , Torasémide/composition chimique , Cristallisation/méthodes , Sels/composition chimique , Liaison hydrogène , Diurétiques/composition chimique , Maléates/composition chimique , Biodisponibilité
13.
Front Med (Lausanne) ; 11: 1442065, 2024.
Article de Anglais | MEDLINE | ID: mdl-39234046

RÉSUMÉ

The high prevalence of acute kidney injury (AKI) in ICU patients emphasizes the need to understand factors influencing continuous renal replacement therapy (CRRT) circuit lifespan for optimal outcomes. This review examines key pharmacological interventions-citrate (especially in regional citrate anticoagulation), unfractionated heparin (UFH), low molecular weight heparin (LMWH), and nafamostat mesylate (NM)-and their effects on filter longevity. Citrate shows efficacy with lower bleeding risks, while UFH remains cost-effective, particularly in COVID-19 cases. LMWH is effective but associated with higher bleeding risks. NM is promising for high-bleeding risk scenarios. The review advocates for non-tunneled, non-cuffed temporary catheters, especially bedside-inserted ones, and discusses the advantages of surface-modified dual-lumen catheters. Material composition, such as polysulfone membranes, impacts filter lifespan. The choice of treatment modality, such as Continuous Veno-Venous Hemodialysis (CVVHD) or Continuous Veno-Venous Hemofiltration with Dialysis (CVVHDF), along with the management of effluent volume, blood flow rates, and downtime, are critical in prolonging filter longevity in CRRT. Patient-specific conditions, particularly the type of underlying disease, and the implementation of early mobilization strategies during CRRT are identified as influential factors that can extend the lifespan of CRRT filters. In conclusion, this review offers insights into factors influencing CRRT circuit longevity, supporting evidence-based practices and suggesting further multicenter studies to guide ICU clinical decisions.

14.
Environ Pollut ; 362: 124946, 2024 Sep 14.
Article de Anglais | MEDLINE | ID: mdl-39265765

RÉSUMÉ

Pesticide contamination has emerged as a global threat to humans. Here, we investigate the soil distribution pattern of organic phosphorus pesticide contamination at a pesticide manufacturing site in northern China, exploring their relationships with soil properties and microbial communities. The concentrations of four organic phosphorus pesticides (i.e., phorate, terbuthion, fenitrothion, and parathion) decreased substantially with soil depths from the surface down to 2 m. However, terbuthion, fenitrothion, and parathion had second-peak concentrations at a depth of 8 m. The concentrations of those organic phosphorus pesticides were negatively correlated with soil water content, but positively correlated with sulfide, pH, and total phosphorus. The distribution patterns of organic phosphorus pesticides closely aligned with that of soil organic matter and clay minerals, especially in the presence of montmorillonite, kaolinite, and chlorite. Various bacterial genera known to degrade organic phosphorus pesticides, such as Flavobacterium, Bacillus, Acinetobacter, Lactobacillus, Pseudomonas, Sphingomonas, and Thiobacillus, were correlated with these pesticides. Since these genera were among the top 50 abundant genera in our samples, they might play a significant role in the degradation of organic phosphorus pesticides. Together, this study unveils previously unrecognized pesticide-soil-microbe interactions, thus providing an important knowledge basis for environmental remediation strategies.

15.
Nucleic Acids Res ; 2024 Sep 12.
Article de Anglais | MEDLINE | ID: mdl-39268585

RÉSUMÉ

DNA hypermodifications are effective weapons for phages to cope with the defense system of bacteria. The biogenesis of DNA hypermodification in phages involves multiple steps, from the modified deoxynucleotide monophosphates to the final hypermodification on the DNA chains. PseudomonasPaMx11 gp46 and gp47 encode the enzymes for sequentially converting 5-phosphomethyl-2'-deoxyuridine to 5-Nα-glycinylthymidine and 5-aminomethyl-2'-deoxyuridine. Here, we have determined the crystal structures of gp46 and gp47 in their apo and double-stranded DNA (dsDNA)-bound forms. We uncovered their dsDNA recognition properties and identified the critical residues for the catalytic reactions. Combined with in vitro biochemical studies, we proposed a plausible reaction scheme for gp46 and gp47 in converting these DNA hypermodifications. Our studies will provide the structural basis for future bioengineering of the synthetic pathway of hypermodification and identifying new modifications in mammals by enzyme-assisted sequencing methods.

16.
Health Qual Life Outcomes ; 22(1): 78, 2024 Sep 12.
Article de Anglais | MEDLINE | ID: mdl-39267044

RÉSUMÉ

BACKGROUND: There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities. METHODS: Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity. RESULTS: The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm2/m2, P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index. CONCLUSIONS: Muscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL.


Sujet(s)
Cirrhose du foie , Muscles squelettiques , Qualité de vie , Sarcopénie , Humains , Mâle , Femelle , Adulte d'âge moyen , Sarcopénie/psychologie , Cirrhose du foie/psychologie , Cirrhose du foie/complications , Muscles squelettiques/physiopathologie , Facteurs sexuels , Sujet âgé , Hospitalisation/statistiques et données numériques , Enquêtes et questionnaires
17.
Muscle Nerve ; 2024 Sep 06.
Article de Anglais | MEDLINE | ID: mdl-39239811

RÉSUMÉ

INTRODUCTION/AIMS: Motor neuron disease (MND) is a progressive neurodegenerative condition with a limited life expectancy. There is very little data on mortality and its associated factors beyond 30 days following gastrostomy. We explored the demographic, clinical, and nutritional predictors for early mortality at 30, 90, and 180 days following gastrostomy in these patients. METHODS: This was a retrospective study involving 94 MND patients in Western Australia who underwent gastrostomy between 2015 and 2021. Patients were divided into two groups based on mortality at 30, 90, and 180 days post-gastrostomy. T-test (or Mann-Whitney), chi-square test and Fisher's exact test were used for detecting between-group differences in various factors. Multivariable logistic regression was used to identify factors associated with post-gastrostomy mortality at 90 and 180 days. RESULTS: No mortality was attributable to gastrostomy-related complications. Lower forced vital capacity (FVC) (p = .039) and greater weight loss (%) (p = .022) from diagnosis to gastrostomy were observed in those who died within 30 days post-gastrostomy. Older age (p = .022), male sex (p = .041), lower FVC (p = .04), requiring but not tolerating noninvasive ventilation (p = .035), and greater weight loss (%) (p = .012) were independent predictors of 90-day post-gastrostomy mortality. However, only older age (p = .01) and greater weight loss (p = .009) were predictors of mortality at 180 days post-gastrostomy. DISCUSSION: Our data indicated that mortality at 90 and 180 days was influenced by the weight loss (%) from diagnosis to gastrostomy, highlighting the importance of nutritional care in the MND population. Gastrostomy placement prior to substantial weight loss may reduce the risk of weight loss-associated mortality and warrants further investigation.

18.
Int J Pharm ; 665: 124655, 2024 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-39244072

RÉSUMÉ

The efficient elimination of bacteria within the dentinal tubules has been hindered by the poor deposition and short residence of disinfecting agents. Meanwhile, the current irrigant (e.g., NaClO, 5.25 %) shows severe adverse effects on the surrounding soft tissues because of its inherent high irritancy. To address this issue, this work reports an in situ generated sonosensitizer to handle the biofilm in dentinal tubules with minimal adverse effects. The production of nanoscale sonosensitizer involves the concurrent delivery of H2O2 (0.01 %), ferrocene derivative (Fc), and indocyanine green (ICG). With ultrasound treatment, the reaction between H2O2 and Fc liberated Fe3+ that was further complexed with ICG to generate the nanoscale sonosensitizer in situ, followed by singlet oxygen production for potent disinfecting action. Because the above cascade reactions occur within the confined dentinal tubules, the generated ICG-Fe3+ nanosensitizer would show prolonged retention therein. The anti-bacterial potency of nanosensitizer was demonstrated in petrodish and ex vivo biofilm models. Meanwhile, the transmission electron microscope imaging of biofilm and cytotoxicity assay in L929 fibroblast cells proved the superiority of nanosensitizer against NaClO regarding adverse effects. The current work opens new avenues of biofilm elimination in dentinal tubules, showing a high translation potential.

19.
BMC Geriatr ; 24(1): 743, 2024 Sep 07.
Article de Anglais | MEDLINE | ID: mdl-39244553

RÉSUMÉ

PURPOSE: This study aimed to develop a Quality of Life (QOL) assessment scale for older patients with Neuro-co-Cardiological Diseases (NCCD) and to evaluate the reliability and validity of the scale. METHOD: The study participants were derived from the Elderly Individuals with NCCD Registered Cohort Study (EINCCDRCS), a multicenter registry of patients with NCCD. The preliminary testing of the questionnaire was conducted among 10 older individuals aged 65 years and older who had NCCD and were recruited from the registry. Other patients who met the inclusion criteria participated in the field testing. After verifying the unidimensionality, local independence, and monotonicity assumptions of the scale, we employed the Rasch model within Item Response Theory framework to assess the quality of the scale through methods including internal consistency, criterion validity, Wright map, and item functioning differential. Subsequently, we assessed the construct validity of the scale by combining exploratory factor analysis with confirmatory factor analysis. RESULTS: Based on well-validated scales such as the short-form WHOQOL-OLD, HeartQOL, IQCODE, and SF-36, an original Neuro-co-Cardiological Diseases Quality of Life scale (NCCDQOL) was developed. 196 individuals from the EINCCDRCS were included in the study, with 10 participating in the preliminary testing and 186 in the field testing. Based on the results of the preliminary testing, the original questionnaire was refined through item deletion and adjustment, resulting in an 11-item NCCDQOL questionnaire. The Rasch analysis of the field testing data led to the removal of 21 misfitting individuals. The NCCDQOL demonstrated a four-category structure, achieved by combining two response categories. This structure aligned with the assumptions of unidimensionality, local independence, and monotonicity. The NCCDQOL also exhibited good validity and reliability. CONCLUSION: The revised NCCDQOL questionnaire demonstrated good reliability and validity in the Rasch model, indicating promising potential for clinical application.


Sujet(s)
Qualité de vie , Humains , Qualité de vie/psychologie , Sujet âgé , Mâle , Femelle , Enquêtes et questionnaires/normes , Études de cohortes , Sujet âgé de 80 ans ou plus , Maladies du système nerveux/psychologie , Maladies du système nerveux/diagnostic , Cardiopathies/psychologie , Cardiopathies/diagnostic , Reproductibilité des résultats , Enregistrements , Comorbidité
20.
Front Nutr ; 11: 1440279, 2024.
Article de Anglais | MEDLINE | ID: mdl-39246396

RÉSUMÉ

Less research has been conducted on the association between camellia oil's (CO) phenolic composition and antioxidant capability. In this study, the phenolic profile of CO and its connection to antioxidant capacity were examined utilizing a combination of widely-targeted phenolic metabolomics and multivariate statistical analysis. A total of 751 phenolics were discovered. The WGCNA was used to link phenols to antioxidants, yielding 161 antioxidant-related phenols from the blue module. In response to several antioxidant assays, 59 (FRAP), 59 (DPPH), and 53 (ABTS) phenolics were identified as differential phenolic markers (DPMs). Further stepwise multiple linear regression revealed six DPMs that substantially influenced the antioxidant capacities. Nine metabolic pathways and their associated network mechanisms for the most significant phenolics were developed. This study sheds light on the phenolic content of CO, elucidates their role in antioxidant activity, and lays the groundwork for improving extraction techniques and generating improved product.

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