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1.
J Agric Food Chem ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814711

ABSTRACT

Ketopantoate hydroxymethyltransferase (KPHMT) plays a pivotal role in d-pantothenic acid biosynthesis. Most KPHMTs are homodecamers with low thermal stability, posing challenges for protein engineering and limiting output enhancement. Previously, a high-enzyme activity KPHMT mutant (K25A/E189S) from Corynebacterium glutamicum was screened as mother strain (M0). Building upon this strain, our study focused on interface engineering modifications, employing a multifaceted approach including integrating folding-free energy calculation, B-factor analysis, and conserved site analysis. Preliminary screening led to the selection of five mutants in the interface─E106S, E98T, E98N, S247I, and S247D─showing improved thermal stability, culminating in the double-site mutant M8 (M0-E98N/S247D). M8 exhibited a T1/2 value of 288.79 min at 50 °C, showing a 3.29-fold increase compared to M0. Meanwhile, the Tm value of M8 was elevated from 53.2 to 59.6 °C. Investigations of structural and molecular dynamics simulations revealed alterations in surface electrostatic charge distribution and the formation of increased hydrogen bonds between subunits, contributing to enhanced thermal stability. This investigation corroborates the efficacy of interface engineering modifications in bolstering KPHMT stability while showing its potential for positively impacting industrial d-pantothenic acid synthesis.

2.
BMC Psychiatry ; 24(1): 263, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594663

ABSTRACT

BACKGROUND: Highly resilient adolescents with type 1 diabetes have been proved to achieve within-target glycemic outcomes and experience high quality of life. The ecological resilience model for adolescents with type 1 diabetes was developed in this study. It aims to increase our understanding of how resilience is both positively and negatively affected by internal and environmental ecological factors. METHODS: This cross-sectional study surveyed 460 adolescents with type 1 diabetes from 36 cities in 11 provinces, China. Participants completed self-report questionnaires on resilience, family functioning, peer support, peer stress, coping style, and demographics. Standard glycated hemoglobin tests were performed on the adolescents. Structural equation modeling was applied to analyze the data. RESULTS: The ecological resilience model for adolescents with type 1 diabetes was a good model with a high level of variance in resilience (62%). Family functioning was the most important predictor of resilience, followed by peer support, positive coping, and peer stress. Moreover, positive coping was the mediator of the relationship between family functioning and resilience. Positive coping and peer stress co-mediated the association between peer support and resilience. CONCLUSIONS: Family functioning, peer relationships, and positive coping are interrelated, which may jointly influence resilience. The findings provide a theoretical basis for developing resilience-promotion interventions for adolescents with type 1 diabetes, which may lead to health improvements during a vulnerable developmental period.


Subject(s)
Diabetes Mellitus, Type 1 , Resilience, Psychological , Humans , Adolescent , Cross-Sectional Studies , Quality of Life , Surveys and Questionnaires , Adaptation, Psychological
3.
BMC Psychiatry ; 24(1): 270, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605327

ABSTRACT

BACKGROUND: Adolescents with type 1 diabetes mellitus suffer from diabetes distress and poor health-related quality of life (HRQOL) since living with the condition that differentiates them from their peers. The present study investigated the effects of peer support and stress on diabetes distress and HRQOL and whether positive coping mediated the effects. METHODS: We used a prospective study design. A total of 201 adolescents with type 1 diabetes mellitus from 20 cities in 4 provinces were recruited.Participants complete two separate surveys at approximately 18-month intervals. The scales employed at both Time 1 and Time 2 included the Diabetes-Specific Peer Support Measure, Diabetes Stress Questionnaire for Youths, Simplified Coping Style Questionnaire, 5-item Problem Areas in Diabetes Scale, and the Diabetes Quality of Life for Youth scale. RESULTS: Baseline peer stress directly predicted diabetes distress and HRQOL at 18 months, even controlling for age, gender, and peer support. However, the direct effect of baseline peer support on 18-month diabetes distress and HRQOL was insignificant. Baseline peer support indirectly affected diabetes distress and HRQOL at 18 months through positive coping, indicating that positive coping plays a mediating role. CONCLUSION: The findings suggest that peer social relationships, especially peer stress, and positive coping are promising intervention targets for adolescents facing challenges in psychosocial adaptation.


Subject(s)
Diabetes Mellitus, Type 1 , Psychological Distress , Humans , Adolescent , Diabetes Mellitus, Type 1/psychology , Quality of Life/psychology , Longitudinal Studies , Adaptation, Psychological , Prospective Studies , Interpersonal Relations , Stress, Psychological/psychology
4.
Front Immunol ; 15: 1375864, 2024.
Article in English | MEDLINE | ID: mdl-38650927

ABSTRACT

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion-a potential target for future immunotherapeutic interventions.


Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular , Liver Neoplasms , Signal Transduction , Humans , CD8-Positive T-Lymphocytes/immunology , Liver Neoplasms/immunology , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/mortality , Prognosis , Receptors, Notch/genetics , Receptors, Notch/metabolism , Gene Expression Regulation, Neoplastic , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Male , Female , Biomarkers, Tumor/genetics , Receptor, Notch1/genetics , Middle Aged
5.
Front Cell Infect Microbiol ; 14: 1376725, 2024.
Article in English | MEDLINE | ID: mdl-38590440

ABSTRACT

In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.


Subject(s)
Guanidines , Piperazines , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Vaccines , Swine , Animals , Porcine respiratory and reproductive syndrome virus/genetics , Cell Line
6.
Bioprocess Biosyst Eng ; 47(6): 841-850, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38676737

ABSTRACT

D-Allulose 3-epimerase (DAE) is a vital biocatalyst for the industrial synthesis of D-allulose, an ultra-low calorie rare sugar. However, limited thermostability of DAEs hinders their use at high-temperature production. In this research, hyperthermophilic TI-DAE (Tm = 98.4 ± 0.7 ℃) from Thermotoga sp. was identified via in silico screening. A comparative study of the structure and function of site-directed saturation mutagenesis mutants pinpointed the residue I100 as pivotal in maintaining the high-temperature activity and thermostability of TI-DAE. Employing TI-DAE as a biocatalyst, D-allulose was produced from D-fructose with a conversion rate of 32.5%. Moreover, TI-DAE demonstrated excellent catalytic synergy with glucose isomerase CAGI, enabling the one-step conversion of D-glucose to D-allulose with a conversion rate of 21.6%. This study offers a promising resource for the enzyme engineering of DAEs and a high-performance biocatalyst for industrial D-allulose production.


Subject(s)
Thermotoga , Thermotoga/enzymology , Thermotoga/genetics , Carbohydrate Epimerases/genetics , Carbohydrate Epimerases/chemistry , Carbohydrate Epimerases/metabolism , Carbohydrate Epimerases/biosynthesis , Racemases and Epimerases/genetics , Racemases and Epimerases/metabolism , Racemases and Epimerases/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/biosynthesis , Fructose/metabolism , Fructose/biosynthesis , Fructose/chemistry , Enzyme Stability , Biocatalysis , Mutagenesis, Site-Directed , Hot Temperature
7.
Biotechnol Adv ; 73: 108353, 2024.
Article in English | MEDLINE | ID: mdl-38593935

ABSTRACT

L-Cysteine and L-methionine, as the only two sulfur-containing amino acids among the canonical 20 amino acids, possess distinct characteristics and find wide-ranging industrial applications. The use of different organisms for fermentative production of L-cysteine and L-methionine is gaining increasing attention, with Escherichia coli being extensively studied as the preferred strain. This preference is due to its ability to grow rapidly in cost-effective media, its robustness for industrial processes, the well-characterized metabolism, and the availability of molecular tools for genetic engineering. This review focuses on the genetic and molecular mechanisms involved in the production of these sulfur-containing amino acids in E. coli. Additionally, we systematically summarize the metabolic engineering strategies employed to enhance their production, including the identification of new targets, modulation of metabolic fluxes, modification of transport systems, dynamic regulation strategies, and optimization of fermentation conditions. The strategies and design principles discussed in this review hold the potential to facilitate the development of strain and process engineering for direct fermentation of sulfur-containing amino acids.


Subject(s)
Escherichia coli , Fermentation , Metabolic Engineering , Metabolic Engineering/methods , Escherichia coli/genetics , Escherichia coli/metabolism , Cysteine/metabolism , Methionine/metabolism , Sulfur/metabolism , Amino Acids/metabolism
8.
Sheng Wu Gong Cheng Xue Bao ; 40(3): 665-686, 2024 Mar 25.
Article in Chinese | MEDLINE | ID: mdl-38545970

ABSTRACT

Erythritol is a novel 4-carbon sugar alcohol produced by microbes in the presence of hyper-osmotic stress. It has excellent potential to serve as an alternative sugar for people with diabetes and also a platform compound for synthesizing various C4 compounds, such as 1, 3-butadiene, 1, 4-butanediol, 2, 5-dihydrofuran and so on. Compared with other polyols, the fermentative production of erythritol is more challenging. Yarrowia lipolytica is the preferred chassis of erythritol biosynthesis for its high-titer and high-productivity. At present, there are still some bottlenecks in the production of erythritol by Y. lipolytica, such as weak metabolic activity, abundant by-products, and low industrial attributes. Progress has been made in tailoring high version strains according to industrial needs. For example, the highest titer of erythritol produced by the metabolically engineered Y. lipolytica reached 196 g/L and 150 g/L, respectively, by using glucose or glycerol as the carbon sources. However, further improving its production performance becomes challenging. This review summarizes the research progress in the synthesis of erythritol by Y. lipolytica from the perspectives of erythritol producing strains, metabolic pathways, modular modifications, and auxiliary strategies to enhance the industrial properties of the engineered strain. Key nodes in the metabolic pathway and their combination strategies are discussed to guide the research on promoting the production of erythritol by Y. lipolytica.


Subject(s)
Yarrowia , Humans , Yarrowia/genetics , Yarrowia/metabolism , Erythritol/metabolism , Metabolic Engineering , Fermentation , Carbon/metabolism
9.
Ying Yong Sheng Tai Xue Bao ; 35(2): 457-468, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38523104

ABSTRACT

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.


Subject(s)
Ecosystem , Rivers , Conservation of Natural Resources/methods , Soil , Carbon , Nitrogen , Phosphorus , China
10.
J Hazard Mater ; 468: 133784, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38382338

ABSTRACT

The relationship between PM2.5 and metabolic diseases, including type 2 diabetes (T2D), has become increasingly prominent, but the molecular mechanism needs to be further clarified. To help understand the mechanistic association between PM2.5 exposure and human health, we investigated short-term PM2.5 exposure trajectory-related multi-omics characteristics from stool metagenome and metabolome and serum proteome and metabolome in a cohort of 3267 participants (age: 64.4 ± 5.8 years) living in Southern China. And then integrate these features to examine their relationship with T2D. We observed significant differences in overall structure in each omics and 193 individual biomarkers between the high- and low-PM2.5 groups. PM2.5-related features included the disturbance of microbes (carbohydrate metabolism-associated Bacteroides thetaiotaomicron), gut metabolites of amino acids and carbohydrates, serum biomarkers related to lipid metabolism and reducing n-3 fatty acids. The patterns of overall network relationships among the biomarkers differed between T2D and normal participants. The subnetwork membership centered on the hub nodes (fecal rhamnose and glycylproline, serum hippuric acid, and protein TB182) related to high-PM2.5, which well predicted higher T2D prevalence and incidence and a higher level of fasting blood glucose, HbA1C, insulin, and HOMA-IR. Our findings underline crucial PM2.5-related multi-omics biomarkers linking PM2.5 exposure and T2D in humans.


Subject(s)
Diabetes Mellitus, Type 2 , Adult , Middle Aged , Aged , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Multiomics , China/epidemiology , Biomarkers , Particulate Matter
11.
Clin Case Rep ; 12(2): e8555, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38410658

ABSTRACT

The second distobuccal canal in the maxillary first molar is often missed because of the low prevalence rate (0%-4%). The article reports this kind of variation in one case. Promising outcomes have continued up to the present (2-year follow-up).

12.
Biotechnol J ; 19(2): e2300648, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38403408

ABSTRACT

L-Cysteine production through fermentation stands as a promising technology. However, excessive accumulation of L-cysteine poses a challenge due to the potential to inflict damage on cellular DNA. In this study, we employed a synergistic approach encompassing atmospheric and room temperature plasma mutagenesis (ARTP) and adaptive laboratory evolution (ALE) to improve L-cysteine tolerance in Escherichia coli. ARTP-treated populations obtained substantial enhancement in L-cysteine tolerance by ALE. Whole-genome sequencing, transcription analysis, and reverse engineering, revealed the pivotal role of an effective export mechanism mediated by gene eamB in augmenting L-cysteine resistance. The isolated tolerant strain, 60AP03/pTrc-cysEf , achieved a 2.2-fold increase in L-cysteine titer by overexpressing the critical gene cysEf during batch fermentation, underscoring its enormous potential for L-cysteine production. The production evaluations, supplemented with L-serine, further demonstrated the stability and superiority of tolerant strains in L-cysteine production. Overall, our work highlighted the substantial impact of the combined ARTP and ALE strategy in increasing the tolerance of E. coli to L-cysteine, providing valuable insights into improving L-cysteine overproduction, and further emphasized the potential of biotechnology in industrial production.


Subject(s)
Cysteine , Escherichia coli , Escherichia coli/genetics , Escherichia coli/metabolism , Cysteine/metabolism , Temperature , Mutagenesis , Fermentation
13.
Proteomics ; 24(6): e2300242, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38171885

ABSTRACT

Clear cell ovarian carcinoma (CCOC) is a relatively rare subtype of ovarian cancer (OC) with high degree of resistance to standard chemotherapy. Little is known about the underlying molecular mechanisms, and it remains a challenge to predict its prognosis after chemotherapy. Here, we first analyzed the proteome of 35 formalin-fixed paraffin-embedded (FFPE) CCOC tissue specimens from a cohort of 32 patients with CCOC (H1 cohort) and characterized 8697 proteins using data-independent acquisition mass spectrometry (DIA-MS). We then performed proteomic analysis of 28 fresh frozen (FF) CCOC tissue specimens from an independent cohort of 24 patients with CCOC (H2 cohort), leading to the identification of 9409 proteins with DIA-MS. After bioinformatics analysis, we narrowed our focus to 15 proteins significantly correlated with the recurrence free survival (RFS) in both cohorts. These proteins are mainly involved in DNA damage response, extracellular matrix (ECM), and mitochondrial metabolism. Parallel reaction monitoring (PRM)-MS was adopted to validate the prognostic potential of the 15 proteins in the H1 cohort and an independent confirmation cohort (H3 cohort). Interferon-inducible transmembrane protein 1 (IFITM1) was observed as a robust prognostic marker for CCOC in both PRM data and immunohistochemistry (IHC) data. Taken together, this study presents a CCOC proteomic data resource and a single promising protein, IFITM1, which could potentially predict the recurrence and survival of CCOC.


Subject(s)
Carcinoma , Ovarian Neoplasms , Female , Humans , Prognosis , Proteomics/methods , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Proteome/analysis , Biomarkers , Biomarkers, Tumor
14.
Waste Manag ; 176: 1-10, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38246072

ABSTRACT

With continuous advancements in the zero-waste strategy in China, transportation of fresh municipal solid waste to landfills has ceased in most first-tier cities. Consequently, the production of landfill gas has sharply declined because the supply of organic matter has decreased, rendering power generation facilities idle. However, by incorporating liquefied kitchen and food waste (LKFW), sustainable methane production can be achieved while consuming organic wastewater. In this study, LKFW and water (as a control group) were periodically injected into high and low organic wastes, respectively. The biochemical characteristics of the resulting gas and leachate were analyzed. LKFW used in this research generated 19.5-37.6 L of methane per liter in the post-methane production phase, highlighting the effectiveness of LKFW injection in enhancing the methane-producing capacity of the system. The release of H2S was prominent during both the rapid and post-methane production phases, whereas that of NH3 was prominent in the post-methane production phase. As injection continued, the concentrations of chemical oxygen demand, 5-d biological oxygen demand, total organic carbon, ammonia nitrogen, total nitrogen, and oil in the output leachate decreased and eventually reached levels comparable to those in the water injection cases. After nine rounds of injections, the biologically degradable matter of the two LKFW-injected wastes decreased by 8.2 % and 15.1 %, respectively. This study sheds light on determining the organic load, controlling odor, and assessing the biochemical characteristics of leachate during LKFW injection.


Subject(s)
Refuse Disposal , Water Pollutants, Chemical , Solid Waste , Refuse Disposal/methods , Food Loss and Waste , Food , Bioreactors , Water Pollutants, Chemical/analysis , Waste Disposal Facilities , Methane/analysis , Water , Nitrogen
15.
Innovation (Camb) ; 5(1): 100544, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38235188

ABSTRACT

Amyloid-ß, tau pathology, and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease (AD). However, these proteins represent only a fraction of the complex biological processes underlying AD, and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers. More AD-specific early diagnostic and disease staging biomarkers are needed. In this study, we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid (CSF) and serum samples in a discovery cohort comprising 98 participants. Candidate biomarkers were validated by parallel reaction monitoring-based targeted proteomic assays in an independent multicenter cohort comprising 288 participants. We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort, identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers, respectively. In the validation cohort, 58 and 21 CSF proteins, as well as 12 and 18 serum proteins, were verified as early diagnostic and staging biomarkers, respectively. Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment (MCI) due to AD from normal cognition with areas under the curve of 0.984 and 0.881, respectively. The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases. Moreover, we identified 21 CSF and 18 serum stage-associated proteins reflecting AD stages. Our findings provide a foundation for developing blood-based tests for AD screening and staging in clinical practice.

16.
Aging Cell ; 23(2): e14035, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37970652

ABSTRACT

The role of circulatory proteomics in osteoporosis is unclear. Proteome-wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, and the 2nd, and 3rd follow-ups (7704 person-tests) in the prospective Chinese cohorts with 9.8 follow-up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at follow-ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the osteoporosis (OP)-related proteomic features. The relationships between serum proteins and BMD in the two cohorts were estimated by linear mixed-effects model (LMM). Meta-analysis was then performed to explore the combined associations. We identified 53 proteins associated with osteoporosis using LightGBM, and a meta-analysis showed that 22 of these proteins illuminated a significant correlation with BMD (p < 0.05). The most common proteins among them were PHLD, SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified proteins were used to generate the biological age (BA) of bone. Each 1 SD-year increase in KDM-Proage was associated with higher risk of LS-OP (hazard ratio [HR], 1.25; 95% CI, 1.14-1.36, p = 4.96 × 10-06 ), and FN-OP (HR, 1.13; 95% CI, 1.02-1.23, p = 9.71 × 10-03 ). The findings uncovered that the apolipoproteins, zymoproteins, complements, and binding proteins presented new mechanistic insights into osteoporosis. Serum proteomics could be a crucial indicator for evaluating bone aging.


Subject(s)
Osteoporosis , Proteome , Humans , Prospective Studies , Proteomics , Chromatography, Liquid , Tandem Mass Spectrometry , Osteoporosis/genetics , Aging
17.
JACC Clin Electrophysiol ; 10(2): 346-355, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37999672

ABSTRACT

BACKGROUND: Low-level transcutaneous stimulation of the auricular branch of the vagus nerve at the tragus is antiarrhythmic and anti-inflammatory in animals and humans. Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS). OBJECTIVES: In this study the authors conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of tVNS on POTS over a 2-month period relative to sham stimulation. METHODS: tVNS (20 Hz, 1 mA below discomfort threshold) was delivered using an ear clip attached to either the tragus (active; n = 12) or the ear lobe (sham; n = 14) for 1 hour daily over a 2-month period. Postural tachycardia was assessed during the baseline and 2-month visit. Heart rate variability based on 5-minute electrocardiogram, serum cytokines, and antiautonomic autoantibodies were measured at the respective time points. RESULTS: Mean age was 34 ± 11 years (100% female; 81% Caucasian). Adherence to daily stimulation was 83% in the active arm and 86% in the sham arm (P > 0.05). Postural tachycardia was significantly less in the active arm compared with the sham arm at 2 months (mean postural increase in heart rate 17.6 ± 9.9 beats/min vs 31.7 ± 14.4 beats/min; P = 0.01). Antiadrenergic autoantibodies and inflammatory cytokines were lower in the active arm compared with the sham arm at 2 months (P < 0.05). Heart rate variability was better in the active arm. No device-related side effects were observed. CONCLUSIONS: Our results support the emerging paradigm of noninvasive neuromodulation to treat POTS. Mechanistically, this effect appears to be related to reduction of antiautonomic autoantibodies and inflammatory cytokines, and improvement in autonomic tone. Further studies are warranted. (Autoimmune Basis for Postural Tachycardia Syndrome; NCT05043051).


Subject(s)
Postural Orthostatic Tachycardia Syndrome , Vagus Nerve Stimulation , Humans , Animals , Female , Young Adult , Adult , Middle Aged , Male , Vagus Nerve Stimulation/adverse effects , Vagus Nerve Stimulation/methods , Postural Orthostatic Tachycardia Syndrome/therapy , Autoantibodies , Cytokines , Tachycardia/therapy
18.
J Clin Endocrinol Metab ; 109(3): e1151-e1158, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-37878955

ABSTRACT

CONTEXT: Prediabetes is associated with an increased risk of physical disability, yet no studies have assessed the extent to which muscle quality, a measure reflecting muscle functionality, was altered in prediabetes and its specific phenotype. OBJECTIVE: We evaluated their associations in a general US population with mediation analysis. METHODS: This was a cross-sectional study based on the National Health and Nutrition Examination Survey 2011-2014. Participants with prediabetes were stratified as having an isolated defect (impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired hemoglobin A1c [IA1c]), 2 defects (IFG + IGT, IFG + IA1c, or IGT + IA1c), or all defects (IFG + IGT + IA1c). Muscle quality was calculated as dominant grip strength divided by dominant arm muscle mass measured by dual-energy X-ray absorptiometry. RESULTS: We included 2351 participants (938 with prediabetes and 1413 with normoglycemia). Despite higher grip strength and larger arm muscle mass, arm muscle quality was lower in prediabetes and all prediabetes phenotypes (except for IGT) than normoglycemia (all P < .04), and was unrelated to prediabetes awareness. Arm muscle quality was decreased and the odds of low arm muscle quality was increased in prediabetes with increasing numbers of glucometabolic defects (both P < .001), with insulin resistance being the predominant mediator. HbA1c-defined prediabetes (IA1c) had lower arm muscle quality and higher odds of low arm muscle quality than blood glucose-defined prediabetes (IFG, IGT, or IFG + IGT). CONCLUSION: Muscle quality was impaired in prediabetes and its specific phenotype. Relative to blood glucose, elevated HbA1c might be a better predictor of reduced muscle quality.


Subject(s)
Glucose Intolerance , Prediabetic State , Humans , Blood Glucose , Glycated Hemoglobin , Cross-Sectional Studies , Mediation Analysis , Nutrition Surveys , Muscles , Phenotype , Fasting
19.
Trends Microbiol ; 32(3): 292-301, 2024 03.
Article in English | MEDLINE | ID: mdl-37798168

ABSTRACT

Conditionally replicating viruses (CRVs) are a type of virus with one or more essential gene functions that are impaired resulting in the disruption of viral genome replication, protein synthesis, or virus particle assembly. CRVs can replicate only if the deficient essential genes are supplied. CRVs are widely used in biomedical research, particularly as vaccines. Traditionally, CRVs are generated by creating complementary cell lines that provide the impaired genes. With the development of biotechnology, novel techniques have been invented to generate CRVs, such as targeted protein degradation (TPD) technologies and premature termination codon (PTC) read-through technologies. The advantages and disadvantages of these novel technologies are discussed. Finally, we provide perspectives on what challenges need to be overcome for CRVs to reach the market.


Subject(s)
Vaccines , Viruses , Viruses/genetics , Virus Replication/genetics , Cell Line
20.
Chemistry ; 30(15): e202303688, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38102885

ABSTRACT

Covalent organic frameworks (COFs) are porous organic materials with well-defined and uniform structure. The material is an excellent candidate as a solid adsorbent for iodine adsorption. In the present study, we report the synthesis of COF with porphyrin moiety, TF-TA-COF, by solvothermal reaction, which was characterized by XRD, solid-state 13 C NMR, IR, TGA, and nitrogen adsorption-desorption analysis. TF-TA-COF showed a high specific surface area of 443 m2 g-1 , and exhibited good adsorption performance for iodine vapor, with an adsorption capacity of 2.74 g g-1 . XPS and Raman spectrum indicated that a hybrid of physisorption and chemisorption took place between host COF and iodine molecules. The electric properties of iodine-loaded TF-TA-COF were also studied. After doped with iodine, the conductivity of the material increased by more than 5 orders of magnitude. The photoconductivity of I2 -doped COF was also studied and TF-TA-COF showed doping-enhanced photocurrent generation.

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