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1.
Org Lett ; 26(29): 6263-6268, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-38995695

ABSTRACT

A metal-free cascade of α-acyloxylation/carboxamidation of I(III)/S(VI)-ylides, carboxylic acids, and isonitriles via a Passerini-like multicomponent reaction is reported. Unexpectedly, [3 + 1+1] cyclization involving I(III)/S(VI)-ylides and two molecules of ethyl isocyanoacetate was observed. The strategy allows for the synthesis of unsymmetrical α,α-disubstituted ketones and functionalized pyrroles with up to 99% yield and wide substrate compatibility. Notably, the procedure has been extended to the late-stage modification of drugs and natural products, offering an elegant complement to the classic Passerini reaction.

2.
Int J Biol Macromol ; 276(Pt 2): 134000, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39032878

ABSTRACT

The recovery of silver ions from wastewater is of great importance due to their adverse environmental impact and significant economic value. This paper introduces a novel adsorbent (CS-AHMT) that can be easily synthesized via a one-step functionalization of chitosan with 4-Amino-3-hydrazino-1,2,4-triazol-5-thiol to efficiently recover silver ions from actual wastewater. CS-AHMT demonstrated superior adsorption performance, achieving an adsorption capacity of 241.4 mg·g-1 at pH 5 and 318 K, and the adsorption equilibrium was rapidly attained within 60 to 120 min. Kinetic and isotherm studies indicate that the adsorption process conforms to the pseudo-nth-order (PNO) and Sips models, suggesting a monolayer adsorption that incorporates both physical and chemical processes, with internal mass transfer being the primary rate-limiting step. Electrostatic and coordination interactions are primarily involved in the adsorption mechanism of silver ions on CS-AHMT, as further validated by density functional theory (DFT) calculations. The selectivity and practical applicability of CS-AHMT were confirmed in real wastewater containing high concentrations of competing ions. The findings underscore the potential of CS-AHMT as an effective adsorbent for silver ion recovery in wastewater treatment applications.

3.
Cardiovasc Diabetol ; 23(1): 265, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39026309

ABSTRACT

BACKGROUND: The role of lifestyle factors and their relative contributions to the development and mortality of cardio-renal-metabolic multimorbidity (CRMM) remains unclear. METHODS: A study was conducted with 357,554 UK Biobank participants. CRMM was defined as the coexistence of two or three cardio-renal-metabolic diseases (CRMDs), including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD). The prospective study examined the associations of individual and combined lifestyle scores (diet, alcohol consumption, smoking, physical activity, sedentary behavior, sleep duration and social connection) with longitudinal progression from healthy to first cardio-renal-metabolic disease (FCRMD), then to CRMM, and ultimately to death, using a multistate model. Subsequently, quantile G-computation was employed to assess the relative contribution of each lifestyle factor. RESULTS: During a median follow-up of 13.62 years, lifestyle played crucial role in all transitions from healthy to FCRMD, then to CRMM, and ultimately to death. The hazard ratios (95% CIs) per score increase were 0.91 (0.90, 0.91) and 0.90 (0.89, 0.91) for healthy to FCRMD, and for FCRMD to CRMM, and 0.84 (0.83, 0.86), 0.87 (0.86, 0.89), and 0.90 (0.88, 0.93) for mortality risk from healthy, FCRMD, and CRMM, respectively. Among the seven factors, smoking status contributed to high proportions for the whole disease progression, accounting for 19.88-38.10%. High-risk diet contributed the largest proportion to the risk of transition from FCRMD to CRMM, with 22.53%. Less-frequent social connection contributed the largest proportion to the risk of transition from FCRMD to death, with 28.81%. When we further consider the disease-specific transitions, we find that lifestyle scores had slightly stronger associations with development to T2D than to CVD or CKD. CONCLUSIONS: Our study indicates that a healthy lifestyle may have a protective effect throughout the longitudinal progression of CRMM, informing more effective management and treatment. Smoking status, diet, and social connection played pivotal roles in specific disease transitions.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Disease Progression , Life Style , Multimorbidity , Renal Insufficiency, Chronic , Humans , Prospective Studies , Male , Female , Middle Aged , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/prevention & control , Longitudinal Studies , Time Factors , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/mortality , Risk Assessment , United Kingdom/epidemiology , Adult , Risk Factors , Prognosis , Risk Reduction Behavior , Smoking/epidemiology , Smoking/adverse effects , Smoking/mortality , Exercise , Databases, Factual , Alcohol Drinking/epidemiology , Alcohol Drinking/adverse effects , Alcohol Drinking/mortality
4.
Aesthetic Plast Surg ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046484

ABSTRACT

OBJECTIVE: The aim of this study was to further guide the diagnosis and treatment programs for clinical facial contouring with injectable fillers by studying the facial contour parameters and proportion preferences consistent with Asian aesthetics. METHODS: A total of 89 subjects (42 males and 47 females aged 20-60 years) who met the inclusion criteria were enrolled in this study. The subjects were grouped by age, sex, and external contour attractiveness score, and the external contour aesthetic parameters and proportions of the subjects in different groups were measured and analysed. RESULTS: The upper facial breadth and lower facial breadth decreased with age, with significant differences between the 50-60-year age group and other age groups (P < 0.01). The nasomental angle showed a decreasing trend with age, with significant differences between the 40-49-year age group and the 20-29-year and 30-39-year age groups (P < 0.05). Males and females were significantly different in calva height, total head height, lower facial height, and calva height to total head height ratio (P < 0.05). With increasing age, the external contour attractiveness scores of males and females both showed decreasing trends, with significant differences between the 50-60-year age group and other age groups (P < 0.05). CONCLUSION: The calva height and the cranioauricular angle have a significant impact on external contour attractiveness. In general, temporal depression, cheek sagging, lateral cheek depression, and an ill-defined mandibular border will occur due to ageing, collagen loss, ligament laxity and sagging, and soft tissue atrophy and sagging, reducing the attractiveness of the external contour. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

5.
BMC Prim Care ; 25(1): 263, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033156

ABSTRACT

BACKGROUND: Missed or delayed child healthcare caused by the COVID-19 lockdown has threatened young children's health and has had an unpredictable influence on caregivers' child healthcare preferences. This study investigated caregivers' child healthcare preferences and the factors that influence them among families with young children (0-3 years) during the lockdown in Shanghai. METHODS: Participants in this cross-sectional study were enrolled through random encounter sampling. Questionnaires were distributed online from June 1 to November 10, 2022, in Shanghai. A total of 477 valid questionnaires were received. The demographics of caregivers and their families, children's characteristics, COVID-19-related information, and caregivers' healthcare preferences were analyzed. The statistical analyses included frequency and percentage, chi-square tests, and multinomial logistic regression. RESULTS: Caregivers preferred child healthcare professionals in the community health service system (CHS; 47.6%) followed by hospital pediatricians (40.0%) during lockdown. Caregivers with the following characteristics preferred CHS: those with an annual household income of CNY 200,000-300,000, those whose youngest children were aged 8-12 months, and those who experienced early childhood physical development issues. Caregivers preferred hospitals if they had experienced healthcare-seeking-related difficulties in accessing professional guidance from hospital pediatricians. CONCLUSIONS: During pandemic lockdowns, policymakers should allocate more resources to CHS to meet caregivers' childcare demands. Moreover, special attention should be given to the healthcare needs for CHS among families with specific demographics. TRIAL REGISTRATION: Approval was obtained from the Ethics Committee of Shanghai Jiao Tong University School of Medicine School of Public Health (SJUPN-202,109; June 1, 2022).


Subject(s)
COVID-19 , Caregivers , Humans , COVID-19/prevention & control , COVID-19/epidemiology , China/epidemiology , Cross-Sectional Studies , Caregivers/psychology , Male , Child, Preschool , Female , Infant , Adult , SARS-CoV-2 , Infant, Newborn , Surveys and Questionnaires , Quarantine/psychology , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Middle Aged , Child Health Services
6.
BMC Cardiovasc Disord ; 24(1): 385, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054422

ABSTRACT

BACKGROUND: Fontan-associated liver disease (FALD) is one of the most common complications following Fontan procedure, but the impact of FALD on survival outcomes remains controversial. The aim of this systematic review and meta-analysis was to examine and quantify the influence of liver disease on the survival of Fontan patients. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed, and relevant human studies published from inception up to 12 August 2022 were searched. Stata (version 17.0) was applied to perform the meta-analysis, using random effects (Mantel-Haenszel) models. The I2 statistic was used to assess the heterogeneity. Subgroup analysis and meta-regression were employed to explore the potential sources of heterogeneity and sensitivity analysis was performed to determine the potential influence of each study on the overall pooled results. RESULTS: A total of 312 records were initially identified and 8 studies involving 2,466 patients were selected for inclusion. Results revealed a significant association between the severity of liver disease following Fontan procedure and mortality, which was confirmed by sensitivity analysis and subgroup analysis assessing post-HT mortality. Meta-regression showed that diagnostic methods for liver disease may be a source of heterogeneity. After removal of the FALD patients identified by international classification of disease codes, heterogeneity was markedly reduced, and the positive association between all-cause mortality and the severity of liver disease became significant. CONCLUSIONS: This meta-analysis showed the severity of liver disease following the Fontan procedure has a significant association with mortality. Lifelong follow-up is necessary and imaging examinations are recommended for routine surveillance of liver disease. Among patients with failing Fontan and advanced liver disease, combined heart-liver transplantation may provide additional survival benefits.


Subject(s)
Fontan Procedure , Heart Defects, Congenital , Liver Diseases , Humans , Fontan Procedure/adverse effects , Fontan Procedure/mortality , Liver Diseases/mortality , Liver Diseases/diagnosis , Liver Diseases/surgery , Liver Diseases/etiology , Risk Factors , Risk Assessment , Heart Defects, Congenital/surgery , Heart Defects, Congenital/mortality , Heart Defects, Congenital/diagnosis , Treatment Outcome , Male , Female , Child , Adolescent , Adult , Young Adult , Time Factors , Child, Preschool , Severity of Illness Index
7.
Front Pharmacol ; 15: 1416403, 2024.
Article in English | MEDLINE | ID: mdl-39021834

ABSTRACT

Diabetic cardiomyopathy (DCM) is a myocardial-specific microvascular disease caused by diabetes that affects the structure and function of the heart and is considered to be the leading cause of morbidity and death in patients with diabetes. Currently, there is no specific treatment or preventive drug for DCM, and there is an urgent need to develop new drugs to treat DCM. Traditional Chinese medicine (TCM) has rich experience in the treatment of DCM, and its characteristics of multi-target, multi-pathway, multi-component, and few side effects can effectively deal with the complexity and long-term nature of DCM. Growing evidence suggests that myocardial fibrosis, inflammation, oxidative stress, apoptosis, cardiac hypertrophy, and advanced glycation end product deposition were the main pathologic mechanisms of DCM. According to the pathological mechanism of DCM, this study revealed the potential of metabolites and prescriptions in TCM against DCM from the perspective of signaling pathways. The results showed that TGF-ß/Smad, NF-κB, PI3K/AKT, Nrf2, AMPK, NLRP3, and Wnt/ß-catenin signaling pathways were the key signaling pathways for TCM treatment of DCM. The aim of this study was to summarize and update the signaling pathways for TCM treatment of DCM, to screen potential targets for drug candidates against DCM, and to provide new ideas and more experimental evidence for the clinical use of TCM treatment of DCM.

8.
J Hazard Mater ; 476: 135204, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39024757

ABSTRACT

Recovering silver from wastewater not only significantly reduces environmental harm but also meets the growing demand for silver in modern industry. Here, a novel metal-organic framework adsorbent (MOF-RD) using rhodanine derivatives as linkers is introduced for the efficient and selective capture of silver ions in real wastewater. The adsorption of MOF-RD followed pseudo-second-order and Sips models, and thermodynamic investigations revealed the process to be endothermic. MOF-RD demonstrated a remarkable adsorption capacity of 707.2 mg·g-1 for Ag(I) at pH 5 and 318 K. The interaction between silver ions and MOF-RD was mainly electrostatic attraction and coordination, with coordination primarily occurring at the CO and CS sites within the rhodanine motif. The practical applicability of MOF-RD for selective adsorption of Ag(I) was validated in actual wastewater with high-concentration competing metal ions. Furthermore, after 10 adsorption-desorption cycle experiments, MOF-RD still retained a strong regenerative capability. The results reveal the good potential of MOF-RD as an adsorbent for selectively recovering Ag(I) from industrial wastewater. Additionally, the strategies and methods adopted in this article also provide new perspectives and technical paths for the separation and recovery of other metal ions in wastewater.

9.
Fish Shellfish Immunol ; 151: 109751, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38971349

ABSTRACT

Egg yolk antibodies (IgY) can be prepared in large quantities and economically, and have potential value as polyvalent passive vaccines (against multiple bacteria) in aquaculture. This study prepared live and inactivated Vibrio fluvialis IgY and immunized Carassius auratus prior to infection with V. fluvialis and Aeromonas hydrophila. The results showed that the two IgY antibodies hold effective passive protective rates against V. fluvialis and A. hydrophila in C. auratus. Further, the serum of C. auratus recognized the two bacteria in vitro, with a decrease in the bacteria content of the kidney. The phagocytic activity of C. auratus plasma was enhanced, with a decrease in the expression of inflammatory and antioxidant factors. Pathological sections showed that the kidney, spleen, and intestinal tissue structures were intact, and apoptosis and DNA damage decreased in kidney cells. Moreover, the immunoprotection conferred by the live V. fluvialis IgY was higher than that of the inactivated IgY. Addition, live V. fluvialis immunity induced IgY antibodies against outer membrane proteins of V. fluvialis were more than inactivated V. fluvialis immunity. Furthermore, heterologous immune bacteria will not cause infection, so V. fluvialis can be used to immunize chickens to obtain a large amount of IgY antibody. These findings suggest that the passive immunization effect of live bacterial IgY antibody on fish is significantly better than that of inactivated bacterial antibody, and the live V. fluvialis IgY hold potential value as polyvalent passive vaccines in aquaculture.


Subject(s)
Aeromonas hydrophila , Egg Yolk , Fish Diseases , Immunoglobulins , Vibrio Infections , Vibrio , Animals , Immunoglobulins/immunology , Immunoglobulins/blood , Vibrio Infections/veterinary , Vibrio Infections/immunology , Vibrio Infections/prevention & control , Vibrio/immunology , Fish Diseases/immunology , Fish Diseases/prevention & control , Egg Yolk/immunology , Aeromonas hydrophila/immunology , Goldfish/immunology , Gram-Negative Bacterial Infections/immunology , Gram-Negative Bacterial Infections/veterinary , Gram-Negative Bacterial Infections/prevention & control , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Immunization, Passive/veterinary , Bacterial Vaccines/immunology , Bacterial Vaccines/administration & dosage
10.
BMC Med Inform Decis Mak ; 24(1): 187, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951831

ABSTRACT

BACKGROUND: Accurate measurement of hemoglobin concentration is essential for various medical scenarios, including preoperative evaluations and determining blood loss. Traditional invasive methods are inconvenient and not suitable for rapid, point-of-care testing. Moreover, current models, due to their complex parameters, are not well-suited for mobile medical settings, which limits the ability to conduct frequent and rapid testing. This study aims to introduce a novel, compact, and efficient system that leverages deep learning and smartphone technology to accurately estimate hemoglobin levels, thereby facilitating rapid and accessible medical assessments. METHODS: The study employed a smartphone application to capture images of the eye, which were subsequently analyzed by a deep neural network trained on data from invasive blood test data. Specifically, the EGE-Unet model was utilized for eyelid segmentation, while the DHA(C3AE) model was employed for hemoglobin level prediction. The performance of the EGE-Unet was evaluated using statistical metrics including mean intersection over union (MIOU), F1 Score, accuracy, specificity, and sensitivity. The DHA(C3AE) model's performance was assessed using mean absolute error (MAE), mean-square error (MSE), root mean square error (RMSE), and R^2. RESULTS: The EGE-Unet model demonstrated robust performance in eyelid segmentation, achieving an MIOU of 0.78, an F1 Score of 0.87, an accuracy of 0.97, a specificity of 0.98, and a sensitivity of 0.86. The DHA(C3AE) model for hemoglobin level prediction yielded promising outcomes with an MAE of 1.34, an MSE of 2.85, an RMSE of 1.69, and an R^2 of 0.34. The overall size of the model is modest at 1.08 M, with a computational complexity of 0.12 FLOPs (G). CONCLUSIONS: This system presents a groundbreaking approach that eliminates the need for supplementary devices, providing a cost-effective, swift, and accurate method for healthcare professionals to enhance treatment planning and improve patient care in perioperative environments. The proposed system has the potential to enable frequent and rapid testing of hemoglobin levels, which can be particularly beneficial in mobile medical settings. TRIAL REGISTRATION: The clinical trial was registered on the Chinese Clinical Trial Registry (No. ChiCTR2100044138) on 20/02/2021.


Subject(s)
Deep Learning , Hemoglobins , Smartphone , Humans , Hemoglobins/analysis , Middle Aged , Male , Mobile Applications , Female
11.
Langmuir ; 40(29): 15301-15309, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38982808

ABSTRACT

Natural mineral-based advanced oxidation processes (AOPs) are now receiving increasing attention for the efficient degradation of pollutants. In this work, we used a common reducing agent (NaBH4) to treat natural Hematite to obtain modified Hematite (Hematite-(R)) and applied it to activate peracetic acid (PAA) for efficient degradation of cefazolin (CFZ). Compared with Hematite, the Hematite-(R)/PAA system increased the degradation rate of CFZ by 21.7% within 80 min under neutral conditions. Scavenging experiments and electron paramagnetic resonance (EPR) technology were introduced to identify the principal roles of 1O2, CH3C(O)OO•, and •OH for CFZ removal over the Hematite-(R)/PAA process. The outstanding capability of Hematite-(R) could be mainly due to the higher percentage of Fe(II) (52%) on the surface of catalysts. Furthermore, the possible degradation pathways of CFZ were explored. Moreover, the Hematite-(R)/PAA process showed a superior CFZ removal efficiency with a wide initial pH scope of 1.0-9.0. The degradation efficiency of CFZ showed a negligible effect in the presence of Cl-, SO42-, and NO3-, while significant inhibition was recorded after the addition of H2PO4- and CO32-. The inhibition of humic acid (HA) on CFZ degradation via the Hematite-(R)/PAA process showed an obvious concentration dependence. This work could provide strong support for the use of natural Hematite in water purification.

12.
J Colloid Interface Sci ; 675: 419-428, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38981251

ABSTRACT

The photocatalytic CO2 reduction reaction is severely limited by sluggish charge kinetics. To address this issue, a strategy utilizing non-metal-doped layered double hydroxide (LDH) has been developed to control the electronic structure of spindle-shaped nanoflowers, resulting in efficient photocatalytic CO2 reduction. The results demonstrate that the designed catalyst yields 263.16 µmol g-1 h-1 for the photoreduction of CO2 to CO. Furthermore, the in situ Fourier transform infrared spectrum (FT-IR) analysis demonstrate that the specific S-ligand (S-bridge) facilitates CO2 activation, ensuring the continuous production of *COOH. The hydrothermal-assisted ionic liquid method proposed in this study offers guidance for modifying catalysts.

14.
Front Cell Dev Biol ; 12: 1428250, 2024.
Article in English | MEDLINE | ID: mdl-38966429

ABSTRACT

Oxeiptosis is a novel cell death pathway that was introduced in 2018. As a form of regulated cell death, it operates independently of caspases and is induced by ROS. Distinguished from other cell death pathways such as apoptosis, necroptosis, pyroptosis, and ferroptosis, oxeiptosis features unique damage causes pivotal genes, and signaling pathways (KEAP1/PGAM5/AIFM1). Emerging studies indicate that oxeiptosis plays a significant role in the progression of various diseases and its regulation could serve as a promising therapeutic target. However, the precise molecular mechanisms underlying oxeiptosis remain to be fully elucidated. In this mini-review, we systematically summarize the latest developments in oxeiptosis-related diseases while detailing the molecular mechanisms and regulatory networks of oxeiptosis. These insights offer a foundation for a deeper understanding of oxeiptosis.

15.
Front Immunol ; 15: 1322159, 2024.
Article in English | MEDLINE | ID: mdl-38966645

ABSTRACT

Background: IgG4-related disease (IgG4-RD) was characterized by single or multiple masses in organs, which may mimic various inflammatory and malignant diseases. Here, we summarize 4 patients with aggressive manifestations of IgG4-RD that mimic nasopharynx cancer to provide some new sights for the diagnosis of IgG4-RD. Case summary: Four patients were included in our series. The age ranged from 53 to 64 years old, and the duration of the disease ranged from 4 to 6 months. The chief complaints included headache, rhinorrhea, or diplopia. All patients had more than 10 IgG4+ plasma cells/HPF in immunohistochemistry with plasma lgG4 levels ranging from 218 mg/dL to 765 mg/dL. All of them met the diagnostic criteria of lgG4-RD. Conclusion: The described case is highly similar to the clinical manifestations of nasopharyngeal carcinoma. Although pathology is the gold standard, there are still limitations. Serological IgG4 can help confirm the diagnosis. Timely diagnosis of IgG4-RD is of great significance in preventing secondary organ damage in patients with active diseases.


Subject(s)
Immunoglobulin G4-Related Disease , Immunoglobulin G , Nasopharyngeal Neoplasms , Humans , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/immunology , Middle Aged , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/diagnosis , Male , Immunoglobulin G/blood , Immunoglobulin G/immunology , Diagnosis, Differential , Female , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/immunology , Plasma Cells/immunology
16.
Int J Mol Med ; 54(3)2024 Sep.
Article in English | MEDLINE | ID: mdl-38963051

ABSTRACT

Lipid metabolism disorders are a major cause of several chronic metabolic diseases which seriously affect public health. Salusin­α, a vasoactive peptide, has been shown to attenuate lipid metabolism disorders, although its mechanism of action has not been reported. To investigate the effects and potential mechanisms of Salusin­α on lipid metabolism, Salusin­α was overexpressed or knocked down using lentiviral vectors. Hepatocyte steatosis was induced by free fatty acid (FFA) after lentiviral transfection into HepG2 cells. The degree of lipid accumulation was assessed using Oil Red O staining and by measuring several biochemical indices. Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semi­quantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism's involvement further. The results showed that Salusin­α significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusin­α increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein­1c, fatty acid synthase and acetyl­CoA carboxylase. The addition of Compound C abrogated the Salusin­α­mediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusin­α activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. This provides insights into the potential mechanism underlying the mechanism by which Salusin­α ameliorates lipid metabolism disorders while identifying a potential therapeutic target.


Subject(s)
AMP-Activated Protein Kinase Kinases , AMP-Activated Protein Kinases , Lipogenesis , Protein Serine-Threonine Kinases , Signal Transduction , Humans , Lipogenesis/genetics , Lipogenesis/drug effects , AMP-Activated Protein Kinases/metabolism , Hep G2 Cells , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Signal Transduction/drug effects , AMP-Activated Protein Kinase Kinases/genetics , Lipid Metabolism Disorders/metabolism , Lipid Metabolism Disorders/genetics , Lipid Metabolism Disorders/drug therapy , Intercellular Signaling Peptides and Proteins/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Lipid Metabolism/drug effects , Lipid Metabolism/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Oxidative Stress/drug effects , Gene Expression Regulation/drug effects
17.
Nat Commun ; 15(1): 5985, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39013850

ABSTRACT

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.


Subject(s)
Aging , Aortic Aneurysm , Aortic Dissection , Cellular Senescence , MicroRNAs , Muscle, Smooth, Vascular , Myosin-Light-Chain Kinase , Signal Transduction , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Mice , Myosin-Light-Chain Kinase/metabolism , Myosin-Light-Chain Kinase/genetics , Aging/genetics , Aging/metabolism , Male , Humans , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Aortic Dissection/metabolism , Aortic Dissection/genetics , Aortic Dissection/pathology , Aortic Aneurysm/metabolism , Aortic Aneurysm/genetics , Aortic Aneurysm/pathology , Myocytes, Smooth Muscle/metabolism , Mice, Inbred C57BL , Female , Transforming Growth Factor beta/metabolism , Disease Models, Animal , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Angiotensin II/metabolism , Calcium-Binding Proteins
18.
World J Gastrointest Surg ; 16(6): 1775-1790, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983337

ABSTRACT

BACKGROUND: Hepatitis is a systemic disease that often results in various comorbidities. Meta-bolic disorders, the most common comorbidities in clinical practice, were selected for this study. AIM: To investigate the causal relationship between comorbidities and hepatitis trea-tment outcomes. METHODS: A total of 23583378 single nucleotide polymorphisms from 1248743 cases and related summaries of genome-wide association studies were obtained from online public databases. A two-sample Mendelian randomization (MR) was performed to investigate causality between exposure [type 2 diabetes mellitus (T2D), hyperlipidemia, and hypertension] and outcome (chronic hepatitis B or C in-fections). RESULTS: The data supported the causal relationship between comorbidities and hepatitis infections, which will affect the severity of hepatitis progression and will also provide a reference for clinical researchers. All three exposures showed a link with progression of both hepatitis B (T2D, P = 0.851; hyperlipidemia, P = 0.596; and hypertension, P = 0.346) and hepatitis C (T2D, P = 0.298; hyperlipidemia, P = 0.141; and hypertension, P = 0.035). CONCLUSION: The results of MR support a possible causal relationship between different ex-posures (T2D, hyperlipidemia, and hypertension) and chronic hepatitis progression; however, the potential mechanisms still need to be elucidated.

19.
Article in English | MEDLINE | ID: mdl-38985557

ABSTRACT

Medical image segmentation provides a reliable basis for diagnosis analysis and disease treatment by capturing the global and local features of the target region. To learn global features, convolutional neural networks are replaced with pure transformers, or transformer layers are stacked at the deepest layers of convolutional neural networks. Nevertheless, they are deficient in exploring local-global cues at each scale and the interaction among consensual regions in multiple scales, hindering the learning about the changes in size, shape, and position of target objects. To cope with these defects, we propose a novel Intra and Inter Attention with Mutual Consistency Learning Network (IIAM). Concretely, we design an intra attention module to aggregate the CNN-based local features and transformer-based global information on each scale. In addition, to capture the interaction among consensual regions in multiple scales, we devise an inter attention module to explore the cross-scale dependency of the object and its surroundings. Moreover, to reduce the impact of blurred regions in medical images on the final segmentation results, we introduce multiple decoders to estimate the model uncertainty, where we adopt a mutual consistency learning strategy to minimize the output discrepancy during the end-to-end training and weight the outputs of the three decoders as the final segmentation result. Extensive experiments on three benchmark datasets verify the efficacy of our method and demonstrate superior performance of our model to state-of-the-art techniques.

20.
Int J Mol Sci ; 25(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39000180

ABSTRACT

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 µg/mL. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be the disruption of the Gram-negative cell membrane.


Subject(s)
Antimicrobial Peptides , Microbial Sensitivity Tests , Animals , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/genetics , Antimicrobial Peptides/metabolism , Escherichia coli/genetics , Escherichia coli/drug effects , Escherichia coli/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Gram-Negative Bacteria/drug effects , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/genetics , Humans
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