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1.
J Infect Dis ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38723186

ABSTRACT

Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas Exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C.trachomatis-infected cells, Z461X-CPP induced cell apoptosis in vitro. In animal model, Z461X significantly shortened the duration of C. trachomatis infection and prevented pathological damage in mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C. trachomatis infection.

2.
Mol Imaging Biol ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760621

ABSTRACT

PURPOSE: Prostate specific membrane antigen (PSMA) has been studied in human breast cancer (BCa) biopsies, however, lack of data on PSMA expression in mouse models impedes development of PSMA-targeted therapies, particularly in improving breast conserving surgery (BCS) margins. This study aimed to validate and characterize the expression of PSMA in murine BCa models, demonstrating that PSMA can be utilized to improve therapies and imaging techniques. METHODS: Murine triple negative breast cancer 4T1 cells, and human cell lines, MDA-MB-231, MDA-MB-468, implanted into the mammary fat pads of BALB/c mice, were imaged by our PSMA targeted theranostic agent, PSMA-1-Pc413, and tumor to background ratios (TBR) were calculated to validate selective uptake. Immunohistochemistry was used to correlate PSMA expression in relation to CD31, an endothelial cell biomarker highlighting neovasculature. PSMA expression was also quantified by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). RESULTS: Accumulation of PSMA-1-Pc413 was observed in 4T1 primary tumors and associated metastases. Average TBR of 4T1 tumors were calculated to be greater than 1.5-ratio at which tumor tissues can be distinguished from normal structures-at peak accumulation with the signal intensity in 4T1 tumors comparable to that in high PSMA expressing PC3-pip tumors. Extraction of 4T1 tumors and lung metastases followed by RT-PCR analysis and PSMA-CD31 co-staining shows that PSMA is consistently localized on tumor neovasculature with no expression in tumor cells and surrounding normal tissues. CONCLUSION: The selective uptake of PSMA-1-Pc413 in these cancer tissues as well as the characterization and validation of PSMA expression on neovasculature in this syngeneic 4T1 model emphasizes their potential for advancements in targeted therapies and imaging techniques for BCa. PSMA holds great promise as an oncogenic target for BCa and its associated metastases.

3.
Molecules ; 29(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38792026

ABSTRACT

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with ß-cyclodextrin (ß-CD) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with ß-CD and HP-ß-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both ß-CD and HP-ß-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-ß-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

4.
World Neurosurg ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38789033

ABSTRACT

Subarachnoid hemorrhage (SAH) is recognized as an especially severe stroke variant, notorious for its high mortality and long-term disability rates, in addition to a range of both immediate and enduring neurological impacts. Over half of the SAH survivors experience varying degrees of neurological disorders, with many enduring chronic neuropsychiatric conditions. Due to the limitations of traditional imaging techniques in depicting subtle changes within brain tissues post-hemorrhage, the accurate detection and diagnosis of white matter (WM) injuries are complicated. Against this backdrop, Diffusion Tensor Imaging (DTI) has emerged as a promising biomarker for structural imaging, renowned for its enhanced sensitivity in identifying axonal damage. This capability positions DTI as an invaluable tool for forming precise and expedient prognoses for SAH survivors. This study synthesizes an assessment of DTI for the diagnosis and prognosis of neurological dysfunctions in patients with SAH, emphasizing the notable changes observed in DTI metrics and their association with potential pathophysiological processes. Despite challenges associated with scanning technology differences and data processing, DTI demonstrates significant clinical potential for early diagnosis of cognitive impairments following SAH and monitoring therapeutic effects. Future research requires the development of highly standardized imaging paradigms to enhance diagnostic accuracy and devise targeted therapeutic strategies for SAH patients. In sum, DTI technology not only augments our understanding of the impact of SAH but also may offer new avenues for improving patient prognoses.

5.
Inorg Chem ; 63(21): 10092-10098, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38748447

ABSTRACT

Exploring efficient alkaline hydrogen oxidation reaction (HOR) electrocatalysts is of great concern for constructing anion exchange membrane fuel cells (AEMFCs). Herein, d-band center modulated PdCo alloys with ultralow Pd content anchored onto the defective carbon support (abbreviated as PdCo/NC hereafter) are proposed as highly efficient HOR catalyst. The as-prepared catalyst exhibits exceptional HOR performance compared to the Pt/C catalyst, achieving thermodynamically spontaneous and kinetically preferential reactions. Specifically, the resultant PdCo/NC demonstrates a marked enhancement in alkaline HOR performance, with the highest mass and specific activities of 1919.6 mA mgPd-1 and 1.9 mA cm-2, 51.1 and 4.2 times higher than those of benchmark of Pt/C, along with an excellent stability in a chronoamperometry test. In the analysis of in situ Raman spectra, it was discovered that tetrahedrally coordinated H-bonded water molecules were formed during the HOR process. This indicates that the promotion of interfacial water molecule formation and enhancement of HOR activities in PdCo/NC are facilitated by defect engineering and the turning of d-band center in PdCo alloy. The essential knowledge obtained in this study could open up a new direction for modifying the electronic structure of cost-effective HOR catalysts through electronic structure engineering.

6.
Arch Microbiol ; 206(6): 279, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805051

ABSTRACT

Yeast, which plays a pivotal role in the brewing, food, and medical industries, exhibits a close relationship with human beings. In this study, we isolated and purified 60 yeast strains from the natural fermentation broth of Sidamo coffee beans to screen for indigenous beneficial yeasts. Among them, 25 strains were obtained through morphological characterization on nutritional agar medium from Wallerstein Laboratory (WL), with molecular biology identifying Saccharomyces cerevisiae strain YBB-47 and the remaining 24 yeast strains identified as Pichia kudriavzevii. We investigated the fermentation performance, alcohol tolerance, SO2 tolerance, pH tolerance, sugar tolerance, temperature tolerance, ester production capacity, ethanol production capacity, H2S production capacity, and other brewing characteristics of YBB-33 and YBB-47. The results demonstrated that both strains could tolerate up to 3% alcohol by volume at a high sucrose mass concentration (400 g/L) under elevated temperature conditions (40 ℃), while also exhibiting a remarkable ability to withstand an SO2 mass concentration of 300 g/L at pH 3.2. Moreover, S. cerevisiae YBB-47 displayed a rapid gas production rate and strong ethanol productivity. whereas P. kudriavzevii YBB-33 exhibited excellent alcohol tolerance. Furthermore, this systematic classification and characterization of coffee bean yeast strains from the Sidamo region can potentially uncover additional yeasts that offer high-quality resources for industrial-scale coffee bean production.


Subject(s)
Ethanol , Fermentation , Pichia , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/isolation & purification , Pichia/metabolism , Pichia/isolation & purification , Pichia/genetics , Pichia/classification , Ethanol/metabolism , Hydrogen-Ion Concentration , Coffee/microbiology , Coffea/microbiology , Temperature , Seeds/microbiology , Hydrogen Sulfide/metabolism
7.
Rehabil Psychol ; 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38602819

ABSTRACT

PURPOSE/OBJECTIVE: This study aims to understand the reciprocal relationships among acceptance of disability, attitudes toward disability, and coping among Chinese adolescents with visual impairments. RESEARCH DESIGN: Adolescents with visual impairments (NT1 = 311, NT2 = 170) from four Chinese special education schools completed three questionnaires twice over 1 year. Cross-lagged panel modeling was carried out to analyze the questionnaire data. RESULTS: The findings revealed that attitudes toward disability and self-directed coping at Time 1 (T1) positively predicted acceptance of disability at Time 2 (T2). Self-directed coping at T1 positively predicted attitudes toward disability at T2, and attitudes toward disability at T1 negatively predicted relinquished-control coping at T2. CONCLUSION/IMPLICATIONS: Visually impaired adolescents' attitudes toward disability and coping serve as antecedents of their acceptance of disability. There is a positive reciprocal relationship between coping and attitudes toward disability. Psychological interventions aimed at optimizing psychosocial adjustment among students with visual impairments may benefit from targeting coping strategies and attitudes toward disability. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

8.
Physiol Plant ; 176(2): e14301, 2024.
Article in English | MEDLINE | ID: mdl-38629128

ABSTRACT

Salt stress is one of the major factors that limits rice production. Therefore, identification of salt-tolerant alleles from wild rice is important for rice breeding. In this study, we constructed a set of chromosome segment substitution lines (CSSLs) using wild rice as the donor parent and cultivated rice Nipponbare (Nip) as the recurrent parent. Salt tolerance germinability (STG) was evaluated, and its association with genotypes was determined using this CSSL population. We identified 17 QTLs related to STG. By integrating the transcriptome and genome data, four candidate genes were identified, including the previously reported AGO2 and WRKY53. Compared with Nip, wild rice AGO2 has a structure variation in its promoter region and the expression levels were upregulated under salt treatments; wild rice WRKY53 also has natural variation in its promoter region, and the expression levels were downregulated under salt treatments. Wild rice AGO2 and WRKY53 alleles have combined effects for improving salt tolerance at the germination stage. One CSSL line, CSSL118 that harbors these two alleles was selected. Compared with the background parent Nip, CSSL118 showed comprehensive salt tolerance and higher yield, with improved transcript levels of reactive oxygen species scavenging genes. Our results provided promising genes and germplasm resources for future rice salt tolerance breeding.


Subject(s)
Genes, Plant , Oryza , Plant Breeding , Salt Tolerance , Oryza/anatomy & histology , Oryza/genetics , Oryza/growth & development , Salt Tolerance/genetics , Chromosomes, Plant/genetics , Alleles , Plant Breeding/methods , Quantitative Trait Loci/genetics , Genotype , Transcriptome , Genome, Plant/genetics , Promoter Regions, Genetic , Gene Expression Regulation, Plant , Germination , Plant Shoots , Plant Roots , Genotyping Techniques , Polymorphism, Genetic , Phenotype
9.
BMC Geriatr ; 24(1): 239, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454354

ABSTRACT

BACKGROUND: There is currently a lack of functional assessment tools based on the International Classification of Functioning, Disability, and Health (ICF) theoretical framework that are specific for older adults. OBJECTIVE: The aim of the present study was to develop Chinese assessment standards of the ICF Geriatric Core Set for functional evaluation of older adults. METHODS: A two-stage study process was conducted to develop the assessment standards of the ICF Geriatric Core Set: establishment of candidate assessment standards, and a modified Delphi consensus process including a pilot survey and two-round formal expert survey. Thirty participants in the field of ICF and geriatric rehabilitation were recruited. The suitability of the assessment standards in the questionnaires was rated using a Likert 5-level scoring method. The arithmetic mean, the full mark ratio and the coefficient of variation (CV) were used as screening indicators for the assessment standards, and modification was made for several standards, in line with the Delphi results and the expert panel discussion. RESULTS: Thirty-three candidate assessment standards belonging to 17 categories were generated. A total of 26 and 24 experts in the field of ICF and geriatric rehabilitation participated in the two-round survey, respectively. Five standards belonging to four categories entered into the second-round survey directly, five standards belonged to five categories entered with minor modification, and nine standards belonging to seven categories were redesigned based on the literature and discussion of the expert panel. In the second-round survey,15 assessment standards belonging to 15 categories met the screening requirements and four assessment standards belonged to the two remaining categories that needed a criterion and which the expert panel discussed for the final decision. CONCLUSIONS: Using the modified Delphi method, the assessment standards of the ICF Geriatric Core Set have been developed.Future work should focus on the reliability and validity of the the assessment standards and their application to the health management of older adults.


Subject(s)
Disability Evaluation , Disabled Persons , Humans , Aged , Delphi Technique , Reproducibility of Results , Disabled Persons/rehabilitation , Surveys and Questionnaires , Activities of Daily Living , International Classification of Functioning, Disability and Health
10.
FASEB J ; 38(6): e23573, 2024 Mar 31.
Article in English | MEDLINE | ID: mdl-38526846

ABSTRACT

Familial hypercholesterolemia (FH) is one of the most prevalent monogenetic disorders leading to cardiovascular disease (CVD) worldwide. Mutations in Ldlr, encoding a membrane-spanning protein, account for the majority of FH cases. No effective and safe clinical treatments are available for FH. Adenine base editor (ABE)-mediated molecular therapy is a promising therapeutic strategy to treat genetic diseases caused by point mutations, with evidence of successful treatment in mouse disease models. However, due to the differences in the genomes between mice and humans, ABE with specific sgRNA, a key gene correction component, cannot be directly used to treat FH patients. Thus, we generated a knock-in mouse model harboring the partial patient-specific fragment and including the Ldlr W490X mutation. LdlrW490X/W490X mice recapitulated cholesterol metabolic disorder and clinical manifestations of atherosclerosis associated with FH patients, including high plasma low-density lipoprotein cholesterol levels and lipid deposition in aortic vessels. Additionally, we showed that the mutant Ldlr gene could be repaired using ABE with the cellular model. Taken together, these results pave the way for ABE-mediated molecular therapy for FH.


Subject(s)
Hypercholesterolemia , Hyperlipoproteinemia Type II , Humans , Mice , Animals , RNA, Guide, CRISPR-Cas Systems , Hyperlipoproteinemia Type II/genetics , Hyperlipoproteinemia Type II/therapy , Mutation , Hypercholesterolemia/genetics , Cholesterol , Receptors, LDL/genetics , Receptors, LDL/metabolism
12.
Angew Chem Int Ed Engl ; 63(18): e202319029, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38449084

ABSTRACT

Electrochemical reduction of nitrate to ammonia (NO3RR) is a promising and eco-friendly strategy for ammonia production. However, the sluggish kinetics of the eight-electron transfer process and poor mechanistic understanding strongly impedes its application. To unveil the internal laws, herein, a library of Pd-based bimetallene with various transition metal dopants (PdM (M=Fe, Co, Ni, Cu)) are screened to learn their structure-activity relationship towards NO3RR. The ultra-thin structure of metallene greatly facilitates the exposure of active sites, and the transition metals dopants break the electronic balance and upshift its d-band center, thus optimizing intermediates adsorption. The anisotropic electronic characteristics of these transition metals make the NO3RR activity in the order of PdCu>PdCo≈PdFe>PdNi>Pd, and a record-high NH3 yield rate of 295 mg h-1 mgcat -1 along with Faradaic efficiency of 90.9 % is achieved in neutral electrolyte on PdCu bimetallene. Detailed studies further reveal that the moderate N-species (*NO3 and *NO2) adsorption ability, enhanced *NO activation, and reduced HER activity facilitate the NH3 production. We believe our results will give a systematic guidance to the future design of NO3RR catalysts.

13.
Bioorg Med Chem Lett ; 102: 129675, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38417632

ABSTRACT

NLRP3 is an intracellular sensor protein that detects a broad range of danger signals and environmental insults. Its activation results in a protective pro-inflammatory response designed to impair pathogens and repair tissue damage via the formation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase 1-dependent secretory release of the pro-inflammatory cytokines IL-1ß and IL-18 as well as to gasdermin d-mediated pyroptotic cell death. Herein, we describe the discovery of a novel indazole series of high affinity, reversible inhibitors of NLRP3 activation through screening of DNA-encoded libraries and the potent lead compound 3 (BAL-0028, IC50 = 25 nM) that was identified directly from the screen. SPR studies showed that compound 3 binds tightly (KD range 104-123 nM) to the NACHT domain of NLRP3. A CADD analysis of the interaction of compound 3 with the NLRP3 NACHT domain proposes a binding site that is distinct from those of ADP and MCC950 and includes specific site interactions. We anticipate that compound 3 (BAL-0028) and other members of this novel indazole class of neutral inhibitors will demonstrate significantly different physical, biochemical, and biological properties compared to NLRP3 inhibitors previously identified.


Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammasomes/metabolism , Sulfonamides , Cytokines/metabolism , Interleukin-1beta/metabolism , Caspase 1 , DNA
14.
Inorg Chem ; 63(10): 4604-4613, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38395777

ABSTRACT

Nontoxic, highly sensitive InP quantum dot (QD) fluorescent immunoassay probes are promising biomedical detection modalities due to their unique properties. However, InP-based QDs are prone to surface oxidation, and the stability of InP QD-based probes in biocompatible environments remains a crucial challenge. Although the thick shell can provide some protection during the phase transfer process of hydrophobic QDs, the photoluminescence quantum yield (PLQY) is generally decreased because of the contradiction between lattice stress relaxation and thick shell growth. Herein, we developed thick-shell InP-based core/shell QDs by inserting a ZnSeS alloy layer. The ternary ZnSeS intermediate shell could effectively facilitate lattice stress relaxation and passivate the defect states. The synthesized InP/ZnSe/ZnSeS/ZnS core/alloy shell/shell QDs (CAS-InP QDs) with nanostructure tailoring revealed a larger size, high PLQY (90%), and high optical stability. After amphiphilic polymer encapsulation, the aqueous CAS-InP QDs presented almost constant fluorescence attenuation and stable PL intensity under different temperatures, UV radiation, and pH solutions. The CAS-InP QDs were excellent labels of the fluorescence-linked immunosorbent assay (FLISA) for detecting C-reactive protein (CRP). The biotin-streptavidin (Bio-SA) system was first introduced in the FLISA to further improve the sensitivity, and the CAS-InP QDs-based SA-Bio sandwich FLISA realized the detection of CRP with an impressive limit of detection (LOD) of 0.83 ng/mL. It is believed that the stable and sensitive InP QD fluorescent probes will drive the rapid development of future eco-friendly, cost-effective, and sensitive in vitro diagnostic kits.


Subject(s)
Nanostructures , Quantum Dots , Biotin , Streptavidin , Fluorescent Dyes , Alloys
15.
Nurse Educ Pract ; 76: 103921, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38395003

ABSTRACT

AIM: The aim of this study was to evaluate the efficacy of evidence-based nursing (EBN) in patients with confirmed stroke. BACKGROUND: After acute hospital treatment, stroke patients often return home for rehabilitation. Stroke ward nursing, demonstrates improved disability-free survival rates. EBN as a new nursing paradigm, rooted in authentic scientific evidence, will transform traditional nursing models. The goal is to advance nursing science, enhance practices and optimize patient outcomes. DESIGN AND METHODS: PubMed, Embase, Cochrane Library and Web of Science were comprehensively searched from the inception to July 2nd, 2023. 13015 patients with confirmed stroke were included, of which 3351 patients were in EBN group, 9664 patients were in the control group. Odd ratio (OR) and standardized mean difference (SMD) and the 95% confidence intervals (CIs) were calculated. RESULTS: Twelve studies were included in this study. The risk of bias in included studies was assessed as low. The OR for cumulative death was 1.61 (95% CI: 0.68, 3.85; z = 1.08, P = 0.2811). The pooled SMD for SF-36 physical component scores was -0.06 (95% CI: -1.15, 0.04; z = -1.11, P = 0.2688). The SMD for SF-36 mental health scores was -0.01 (95% CI: -0.10, 0.09; z = -0.10, P = 0.9207). The SMD for WHOQOL-BREF mentality scores was -0.06 (95% CI: -0.21, 0.10; z = -0.71, P = 0.4754). The SMD for WHOQOL-BREF physiology scores was 1.13 (95% CI: -1.13, 3.39; z = 0.98, P = 0.3283). CONCLUSIONS: EBN is effective in improving psychological status, physical functions and quality of life in patients with stroke in individual studies, efficacy of EBN was not observed in pooled analyses, more evidence-based information is needed to comprehensively assess the efficacy of EBN in stroke patients.


Subject(s)
Stroke Rehabilitation , Stroke , Humans , Quality of Life , Evidence-Based Nursing , Stroke/therapy
16.
Front Psychol ; 15: 1354451, 2024.
Article in English | MEDLINE | ID: mdl-38304918

ABSTRACT

The mental well-being of PhD students is a major concern in higher education. However, very few studies have investigated the influencing factors of PhD students' subjective well-being (SWB) - an important indicator of mental well-being. Even no study on the influencing factors of PhD students' SWB has been undertaken in mainland China. Based on job demands-resources theory, the present study pioneers the investigation of the relationship between PhD students' psychological capital (PsyCap; comprising self-efficacy, hope, resilience, and optimism) and SWB (comprising positive affect, negative affect, and life satisfaction) in mainland China. It further examined the mediating role of academic engagement (comprising vigor, dedication, and absorption) in this relationship. PhD students (n = 376) from two comprehensive universities in Jiangsu province responded to an online survey. The results showed that (1) self-efficacy was positively associated with life satisfaction, hope was positively associated with positive affect, optimism was significantly associated with all three dimensions of SWB, but resilience was not significantly associated with any of the three SWB dimensions; and (2) dedication mediated the relationship between hope and life satisfaction and that between optimism and negative affect and life satisfaction, but vigor and absorption did not mediate any of the PsyCap-SWB relationships. Limitations and practical implications of this study are discussed.

17.
J Nutr ; 154(4): 1309-1320, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38417550

ABSTRACT

BACKGROUND: Obesity caused by the overconsumption of energy-dense foods high in fat and sugar has contributed to the growing prevalence of type 2 diabetes. Betaine, found in food or supplements, has been found to lower blood glucose concentrations, but its exact mechanism of action is not well understood. OBJECTIVES: A comprehensive evaluation of the potential mechanisms by which betaine supplementation improves glucose metabolism. METHODS: Hyperglycemic mice were fed betaine to measure the indexes of glucose metabolism in the liver and muscle. To explore the mechanism behind the regulation of betaine on glucose metabolism, Ribonucleic Acid-Seq was used to analyze the livers of the mice. In vitro, HepG2 and C2C12 cells were treated with betaine to more comprehensively evaluate the effect of betaine on glucose metabolism. RESULTS: Betaine was added to the drinking water of high-fat diet-induced mice, and it was found to reduce blood glucose concentrations and liver triglyceride concentrations without affecting body weight, confirming its hypoglycemic effect. To investigate the specific mechanism underlying its hypoglycemic effect, protein-protein interaction enrichment analysis of the liver revealed key nodes associated with glucose metabolism, including cytochrome P450 family activity, insulin sensitivity, glucose homeostasis, and triglyceride concentrations. The Kyoto Encyclopedia of Genes and Genomes and gene ontogeny enrichment analyses showed significant enrichment of the Notch signaling pathway. These results provided bioinformatic evidence for specific pathways through which betaine regulates glucose metabolism. Key enzyme activities involved in glucose uptake, glycogen synthesis, and glycogenolysis pathways of the liver and muscle were measured, and improvements were observed in these pathways. CONCLUSIONS: This study provides new insight into the mechanisms by which betaine improves glucose metabolism in the liver and muscle and supports its potential as a drug for the treatment of metabolic disorders related to glucose.


Subject(s)
Betaine , Diabetes Mellitus, Type 2 , Mice , Animals , Betaine/metabolism , Mice, Obese , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Liver/metabolism , Triglycerides , Diet, High-Fat/adverse effects , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/pharmacology , Mice, Inbred C57BL , Glucose/metabolism , Lipid Metabolism
18.
BMC Ophthalmol ; 24(1): 38, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38267915

ABSTRACT

BACKGROUND: To report a case of retinitis with multiple intraocular viral infections after second haematopoietic stem cell transplantation. CASE PRESENTATION: A 39-year-old female patient developed retinitis after a second haematopoietic stem cell transplant. Right eye was tested for three viral infections- cytomegalovirus, Epstein‒Barr virus and herpes simplex virus, while left was infected with cytomegalovirus. The patient was subsequently treated with vitreous cavity ganciclovir injections, and 1 week later both eyes tested negative for aqueous humour viruses. DISCUSSION AND CONCLUSION: CMV, EBV and HSV belong to the herpes virus family. They are all commonly observed in the body and represent opportunity infectious viruses. The retinitis they cause have different characteristics. But simultaneous infection of the eye by multiple viruses is quite rare. In this case, three viruses were detected in the patient's eye, but whether the retina was caused by all three viruses at the same time could not be determined. A satisfactory outcome was achieved after treatment with vitreous cavity ganciclovir injection.


Subject(s)
Epstein-Barr Virus Infections , Hematopoietic Stem Cell Transplantation , Retinitis , Virus Diseases , Female , Humans , Adult , Herpesvirus 4, Human , Cytomegalovirus , Simplexvirus , Epstein-Barr Virus Infections/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Retina , Ganciclovir/therapeutic use
19.
J Phys Chem Lett ; 15(3): 733-743, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38226607

ABSTRACT

Solid composite electrolytes (SCEs) synergize inorganic and polymer merits for viable commercial application. However, inferior filler-polymer interfacial stability ultimately leads to the agglomeration of inorganic particles and greatly impedes Li+ migration. Herein, triethoxyvinylsilane (VTEO) is employed to form a strong chemical interaction between poly(vinylene carbonate) (PVC) and montmorillonite (MMT) via in situ solidification, which eliminates the agglomeration and improves interfacial compatibility. Consequently, the obtained solid composite electrolytes (PVC-s-MMT) achieve increased Li+ conductivity (0.4 mS cm-1 at 25 °C), enhanced transference number (0.74), and increased oxidation potential (5.2 V). The Li/PVC-s-MMT/LiFePO4 cells exhibit outstanding cycling performance (>99.5% after 600 cycles) at 1C at room temperature. Moreover, density functional theory (DFT) calculations are applied to uncover the fast interfacial conducting channels of PVC-s-MMT. Our work provides a feasible in situ synthesis method to prepare agglomeration-free SCEs, which is highly compatible with existing battery production processes of liquid electrolytes.

20.
Inorg Chem ; 63(4): 2138-2147, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38237037

ABSTRACT

Expediting the torpid kinetics of the oxygen reduction reaction (ORR) at the cathode with minimal amounts of Pt under acidic conditions plays a significant role in the development of proton exchange membrane fuel cells (PEMFCs). Herein, a novel Pt-N-C system consisting of Pt single atoms and nanoparticles anchored onto the defective carbon nanofibers is proposed as a highly active ORR catalyst (denoted as Pt-N-C). Detailed characterizations together with theoretical simulations illustrate that the strong coupling effect between different Pt sites can enrich the electron density of Pt sites, modify the d-band electronic environments, and optimize the oxygen intermediate adsorption energies, ultimately leading to significantly enhanced ORR performance. Specifically, the as-designed Pt-N-C demonstrates exceptional ORR properties with a high half-wave potential of 0.84 V. Moreover, the mass activity of Pt-N-C reaches 193.8 mA gPt-1 at 0.9 V versus RHE, which is 8-fold greater than that of Pt/C, highlighting the enormously improved electrochemical properties. More impressively, when integrated into a membrane electrode assembly as cathode in an air-fed PEMFC, Pt-N-C achieved a higher maximum power density (655.1 mW cm-2) as compared to Pt/C-based batteries (376.25 mW cm-2), hinting at the practical application of Pt-N-C in PEMFCs.

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