Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 605
Filter
1.
J Exp Med ; 221(8)2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38836810

ABSTRACT

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.


Subject(s)
Intercellular Signaling Peptides and Proteins , Low Density Lipoprotein Receptor-Related Protein-6 , Wnt Signaling Pathway , Animals , Wnt Signaling Pathway/drug effects , Low Density Lipoprotein Receptor-Related Protein-6/metabolism , Low Density Lipoprotein Receptor-Related Protein-6/genetics , Mice , Intercellular Signaling Peptides and Proteins/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Humans , beta Catenin/metabolism , Nail Diseases/metabolism , Nail Diseases/virology , Nail Diseases/pathology , Nails/metabolism , Nails/pathology , Cell Differentiation/drug effects , Mice, Inbred C57BL , Hand, Foot and Mouth Disease/virology , Hand, Foot and Mouth Disease/metabolism , Hand, Foot and Mouth Disease/pathology , Hand, Foot and Mouth Disease/complications , Phosphorylation/drug effects , Coxsackievirus Infections/complications , Coxsackievirus Infections/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Pyridines/pharmacology , Pyrimidines
2.
Mech Ageing Dev ; : 111955, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38852746

ABSTRACT

While high-fat diet (HFD)-induced obesity is a major threat to global public health, the effect of HFD on cognition and insulin signaling during ageing remains controversial. The aim of this study was to characterize the dynamic alterations in cognition and cerebral insulin signaling during 6-month HFD consumption, and to investigate the potential therapeutic target and optimal timing to rescue obesity-related cognitive deficits. In the present study, impaired memory retention induced by 2-month HFD was recovered after 4 months on HFD. Prolonged (6-month) HFD did not further enhance tau hyperphosphorylation and ß-amyloid deposition, which was consistent with the alleviation of memory retention. In brain insulin signaling, 2-month HFD increased IRS-1 and p-IRS-1(Ser307)/IRS-1, while decreasing pAKT(Ser473)/AKT, PI3K and mTOR; 4-month HFD decreased IRS-1 and pAKT(Ser473)/AKT, while increasing AKT; 6-month HFD increased IRS-1, pAKT(Ser473)/AKT, and mTOR, while decreasing p-IRS-1(Ser307)/IRS-1, PI3K and AKT. Notably, bioinformatic analysis revealed a rhythmic process presented only in 4-month HFD group, with Srebf1 emerging as a link between circadian rhythms and insulin signaling pathway. These results suggest that prolonged HFD prevents further cognitive decline and the progression of Alzheimer's disease (AD)-related pathologies during ageing. Moreover, there may be a window for recovery, in which Srebf1 acts as a self-recovery switch to address obesity-related cognitive disorders in elders.

3.
Molecules ; 29(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38731587

ABSTRACT

We aimed to obtain the optimal formula for human milk fat substitute (HMFS) through a combination of software and an evaluation model and further verify its practicability through an animal experiment. The results showed that a total of 33 fatty acid (FA) and 63 triglyceride (TAG) molecular species were detected in vegetable oils. Palmitic acid, oleic acid, linoleic acid, 18:1/16:0/18:1, 18:2/16:0/18:2, 18:1/18:1/18:1 and 18:1/18:2/18:1, were the main molecular species among the FAs and TAGs in the vegetable oils. Based on the HMFS evaluation model, the optimal mixed vegetable oil formula was blended with 21.3% palm oil, 2.8% linseed oil, 2.6% soybean oil, 29.9% rapeseed oil and 43.4% maize oil, with the highest score of 83.146. Moreover, there was no difference in the weight, blood routine indices or calcium and magnesium concentrations in the feces of the mice between the homemade mixed vegetable oil (HMVO) group and the commercial mixed vegetable oil (CMVO) group, while nervonic acid (C24:1) and octanoic acid (C8:0) were absorbed easily in the HMVO group. Therefore, these results demonstrate that the mixing of the different vegetable oils was feasible via a combination of computer software and an evaluation model and provided a new way to produce HMFS.


Subject(s)
Fat Substitutes , Fatty Acids , Milk, Human , Plant Oils , Software , Triglycerides , Humans , Animals , Plant Oils/chemistry , Fatty Acids/chemistry , Milk, Human/chemistry , Mice , Triglycerides/chemistry , Fat Substitutes/chemistry , Palm Oil/chemistry , Soybean Oil/chemistry , Linseed Oil/chemistry , Rapeseed Oil/chemistry , Corn Oil/chemistry , Caprylates/chemistry , Palmitic Acid/chemistry , Oleic Acid/chemistry
4.
Foods ; 13(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38731727

ABSTRACT

Dendrobium nobile Lindl. polysaccharide (DNP1) showed good anti-inflammatory activity in our previous study. In this study, the structural characterization of DNP1 and its mode of action on TLR4 were investigated. Structural characterization suggested that DNP1 was a linear glucomannan composed of (1 → 4)-ß-Manp and (1 → 4)-ß-Glcp residues, and the acetyl group was linked to the C-2 of Manp. The possible repeating structural units of DNP1 were [→4)-2-OAc-ß-Manp-(1→]3 →4)-ß-Glcp-(1→. Surface plasmon resonance (SPR) binding test results showed that DNP1 did not bind directly to TLR4. The TLR4 and MD2 receptor blocking tests confirmed that DNP1 needs MD2 and TLR4 to participate in its anti-inflammatory effect. The binding energy of DNP1 to TLR4-MD2 was -7.9 kcal/mol, indicating that DNP1 could bind to the TLR4-MD2 complex stably. Therefore, it is concluded that DNP1 may play an immunomodulatory role by binding to the TLR4-MD2 complex and inhibiting the TLR4-MD2-mediated signaling pathway.

5.
Aquat Toxicol ; 272: 106959, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38768528

ABSTRACT

As one of the main components of marine pollution, microplastics (MPs) inevitably enter the mussel aquaculture environment. At the same time, pathogenic bacteria, especially pathogens such as Vibrio, can cause illness outbreaks, leading to large-scale death of mussels. The potential harm of MPs and pathogenic bacteria to bivalve remains unclear. This study designed two experiments (1) mussels (Mytilus galloprovincialis) were exposed to 100 particles/L or 1,000 particles/L polymethyl methacrylate (PMMA, 17.01 ± 6.74 µm) MPs and 1 × 107 CFU/mL Vibrio parahaemolyticus at the same time (14 days), and (2) mussels were exposed to 100 particles/L or 1,000 particles/L MPs for a long time (30 days) and then exposed to 1 × 107 CFU/mL V. parahaemolyticus to explore the effects of these two stresses on the mussel immune system. The results showed that after the combined exposure of V. parahaemolyticus and MPs, the lysosomal membrane stability of hemocytes decreased, lysozyme activity was inhibited, and hemocytes were induced to produce more lectins and defensins to fight pathogenic invasion. Long-term exposure to MPs caused a large amount of energy consumption in mussels, inhibited most of the functions of humoral immunity, increased the risk of mussel infection with pathogenic bacteria, and negatively affected mussel condition factor, the number of hemocytes, and the number of byssuses. Mussels may allocate more energy to deal with MPs and pathogenic bacterial infections rather than for growth. Above all, MPs exposure can affect mussel immune function or reduce its stress resistance, which in turn has an impact on mollusk farming.

6.
Nat Commun ; 15(1): 4111, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750018

ABSTRACT

Clarifying migration timing and its link with underlying drivers is fundamental to understanding the evolution of bird migration. However, previous studies have focused mainly on environmental drivers such as the latitudes of seasonal distributions and migration distance, while the effect of intrinsic biological traits remains unclear. Here, we compile a global dataset on the annual cycle of migratory birds obtained by tracking 1531 individuals and 177 populations from 186 species, and investigate how body mass, a key intrinsic biological trait, influenced timings of the annual cycle using Bayesian structural equation models. We find that body mass has a strong direct effect on departure date from non-breeding and breeding sites, and indirect effects on arrival date at breeding and non-breeding sites, mainly through its effects on migration distance and a carry-over effect. Our results suggest that environmental factors strongly affect the timing of spring migration, while body mass affects the timing of both spring and autumn migration. Our study provides a new foundation for future research on the causes of species distribution and movement.


Subject(s)
Animal Migration , Bayes Theorem , Birds , Seasons , Animal Migration/physiology , Animals , Birds/physiology , Body Weight , Time Factors
7.
Food Chem Toxicol ; 189: 114715, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38729342

ABSTRACT

As a commonly used food preservative, glycerol monocaprylate (GMC) has limited information and lacked a comprehensive risk assessment. In this study, we conducted in vitro genotoxicity tests, a 90-day subchronic toxicity study, and dietary exposure assessment in China. Rats (n = 10/sex/group) were orally administered GMC at doses of 1.02, 2.04, and 4.08 g/kg BW/day along with a water and corn oil for 90 days, including satellite groups (n = 5/sex/group) in the control groups and 4.08 g/kg BW dose group for observation after 90 days. Body weight, food consumption, hematology, serum biochemistry, urinalysis, endocrine hormone level and other metrics were examined. GMC did not exhibit genotoxicity based on the genotoxicity tests results, and an acceptable daily intake (ADI) of 40.8 mg/kg BW/day was established based on the 90-day subchronic toxicity study. Estimated daily intake of GMC for general population and consumer population in China were 0.99 mg/kg BW/day and 3.19 mg/kg BW/day respectively, which were significantly lower than the ADI. Our findings suggest that GMC does not pose a known health risk to Chinese consumers at the current usage level.

8.
J Immunol ; 212(12): 1877-1890, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38700398

ABSTRACT

Despite the advances in study on osmotic physiology in bony fish, the mechanism by which the immune system, especially T-cell immunity, adapts and responds to osmotic stress remains unknown. In the current study, we investigated the response of T cells to hyperosmotic stress in the bony fish Nile tilapia (Oreochromis niloticus). As a euryhaline fish, tilapia was able to adapt to a wide range of salinities; however, hypertonic stress caused inflammation and excessive T-cell activation. Furthermore, hypertonic stress increased the expression of IL-17A in T cells, upregulated the transcription factor RORα, and activated STAT3 signaling, along with IL-6- and TGF-ß1-mediated pathways, revealing an enhanced Th17 response in this early vertebrate. These hypertonic stress-induced events collectively resulted in an impaired antibacterial immune response in tilapia. Hypertonic stress elevated the intracellular ROS level, which in turn activated the p38-MK2 signaling pathway to promote IL-17A production by T cells. Both ROS elimination and the p38-MK2 axis blockade diminished the increased IL-17A production in T cells under hypertonic conditions. Moreover, the produced proinflammatory cytokines further amplified the hypertonic stress signaling via the MKK6-p38-MK2 axis-mediated positive feedback loop. To our knowledge, these findings represent the first description of the mechanism by which T-cell immunity responds to hypertonic stress in early vertebrates, thus providing a novel perspective for understanding the adaptive evolution of T cells under environmental stress.


Subject(s)
Inflammation , Osmotic Pressure , Th17 Cells , Tilapia , Animals , Th17 Cells/immunology , Inflammation/immunology , Tilapia/immunology , Signal Transduction/immunology , Lymphocyte Activation/immunology , Interleukin-17/metabolism , Interleukin-17/immunology
9.
Neurochem Res ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38782837

ABSTRACT

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.

10.
Environ Sci Ecotechnol ; 20: 100412, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38560759

ABSTRACT

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018-2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

11.
RSC Adv ; 14(18): 12574-12579, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38638819

ABSTRACT

A KOH mediated mild, efficient, convenient and gram-scalable protocol for the acetylation of alcohols with EtOAc as acetyl source and solvent. Various types of alcohols were successfully transformed into according acetylated products. Good to excellent yields were offered by primary alcohols and low to moderate yields were offered by secondary alcohols.

12.
Metabolites ; 14(4)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38668358

ABSTRACT

During early lactation, dairy cows have a negative energy balance since their energy demands exceed their energy intake: in this study, we aimed to investigate the association between diet and plasma metabolomics profiles and how these relate to energy unbalance of course in the early-lactation stage. Holstein-Friesian cows were randomly assigned to a glucogenic (n = 15) or lipogenic (n = 15) diet in early lactation. Blood was collected in week 2 and week 4 after calving. Plasma metabolite profiles were detected using liquid chromatography-mass spectrometry (LC-MS), and a total of 39 metabolites were identified. Two plasma metabolomic profiles were available every week for each cow. Metabolite abundance and metabolite ratios were used for the analysis using the XGboost algorithm to discriminate between diet treatment and lactation week. Using metabolite ratios resulted in better discrimination performance compared with the metabolite abundances in assigning cows to a lipogenic diet or a glucogenic diet. The quality of the discrimination of performance of lipogenic diet and glucogenic diet effects improved from 0.606 to 0.753 and from 0.696 to 0.842 in week 2 and week 4 (as measured by area under the curve, AUC), when the metabolite abundance ratios were used instead of abundances. The top discriminating ratios for diet were the ratio of arginine to tyrosine and the ratio of aspartic acid to valine in week 2 and week 4, respectively. For cows fed the lipogenic diet, choline and the ratio of creatinine to tryptophan were top features to discriminate cows in week 2 vs. week 4. For cows fed the glucogenic diet, methionine and the ratio of 4-hydroxyproline to choline were top features to discriminate dietary effects in week 2 or week 4. This study shows the added value of using metabolite abundance ratios to discriminate between lipogenic and glucogenic diet and lactation weeks in early-lactation cows when using metabolomics data. The application of this research will help to accurately regulate the nutrition of lactating dairy cows and promote sustainable agricultural development.

13.
Sci Total Environ ; 927: 172300, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38593873

ABSTRACT

The decomposition of ammonia-N to environmental-friendly N2 remains a fundamental problem for water treatment. We proposed a way to selectively and efficiently oxidize ammonia to N2 through an integrated photoeletrocatalysis­chlorine reactions (PECCl) system based on a bifunctional TiO2 nanotube photoanode. The ·OH and HClO can be simultaneously generated on the TiO2 nanotube photoanode in this system, which can in situ form ClO· for efficient ammonia removal. Compared with electrochemical­chlorine (EC-Cl), photocatalysis­chlorine (PC-Cl) and photoelectrocatalysis (PEC) systems, the PEC-Cl system exhibited much higher electrocatalytic activity due to the synergetic effect of photoelectrocatalyst and electrocatalyst in bifunctional TiO2 nanotube electrode. The removal efficiency of ammonia-N and total-N reached 100.0 % and 93.3 % at 0.3 V (vs Ag/AgCl) in the PEC-Cl system. Moreover, the system was efficient under various pH conditions. The reactions between ClO-/ClO· and the N-containing intermediates contributed to the high performance of the system, which expanded the reactions from the electrode surface to the electrolyte. Furthermore, radical scavenging and free chlorine determination experiments confirmed that ClO· and free chlorine were the main active species that enabled the ammonia oxidation. This study presents new understanding on the role of active species for ammonia removal in wastewater.

14.
Int J Biol Macromol ; 267(Pt 2): 131510, 2024 May.
Article in English | MEDLINE | ID: mdl-38608989

ABSTRACT

Bacterial diseases caused substantial yield losses worldwide, with the rise of antibiotic resistance, there is a critical need for alternative antibacterial compounds. Natural products (NPs) from microorganisms have emerged as promising candidates due to their potential as cost-effective and environmentally friendly bactericides. However, the precise mechanisms underlying the antibacterial activity of many NPs, including Guvermectin (GV), remain poorly understood. Here, we sought to explore how GV interacts with Guanosine 5'-monophosphate synthetase (GMPs), an enzyme crucial in bacterial guanine synthesis. We employed a combination of biochemical and genetic approaches, enzyme activity assays, site-directed mutagenesis, bio-layer interferometry, and molecular docking assays to assess GV's antibacterial activity and its mechanism targeting GMPs. The results showed that GV effectively inhibits GMPs, disrupting bacterial guanine synthesis. This was confirmed through drug-resistant assays and direct enzyme inhibition studies. Bio-layer interferometry assays demonstrated specific binding of GV to GMPs, with dependency on Xanthosine 5'-monophosphate. Site-directed mutagenesis identified key residues crucial for the GV-GMP interaction. This study elucidates the antibacterial mechanism of GV, highlighting its potential as a biocontrol agent in agriculture. These findings contribute to the development of novel antibacterial agents and underscore the importance of exploring natural products for agricultural disease management.


Subject(s)
Adenosine/analogs & derivatives , Anti-Bacterial Agents , Ivermectin , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Ivermectin/pharmacology , Ivermectin/analogs & derivatives , Ivermectin/chemistry , Molecular Docking Simulation , Biological Products/pharmacology , Biological Products/chemistry , Microbial Sensitivity Tests , Carbon-Nitrogen Ligases/metabolism , Carbon-Nitrogen Ligases/chemistry , Carbon-Nitrogen Ligases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Mutagenesis, Site-Directed
15.
FEMS Microbiol Ecol ; 100(5)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38599637

ABSTRACT

As an important habitat for microorganisms, the phyllosphere has a great impact on plant growth and health, and changes in phyllosphere microorganisms are closely related to the occurrence of leaf diseases. However, there remains a limited understanding regarding alterations to the microbial community in the phyllosphere resulting from pathogen infections. Here, we analyzed and compared the differences in phyllosphere microorganisms of powdery mildew cucumber from three disease severity levels (0% < L1 < 30%, 30% ≤ L2 < 50%, L3 ≥ 50%, the number represents the lesion coverage rate of powdery mildew on leaves). There were significant differences in α diversity and community structure of phyllosphere communities under different disease levels. Disease severity altered the community structure of phyllosphere microorganisms, Rosenbergiella, Rickettsia, and Cladosporium accounted for the largest proportion in the L1 disease grade, while Bacillus, Pantoea, Kocuria, and Podosphaera had the highest relative abundance in the L3 disease grade. The co-occurrence network analysis of the phyllosphere microbial community indicated that the phyllosphere bacterial community was most affected by the severity of disease. Our results suggested that with the development of cucumber powdery mildew, the symbiotic relationship between species was broken, and the entire bacterial community tended to compete.


Subject(s)
Ascomycota , Cucumis sativus , Microbiota , Plant Diseases , Cucumis sativus/microbiology , Plant Diseases/microbiology , Ascomycota/genetics , Ascomycota/growth & development , Plant Leaves/microbiology , Bacteria/genetics , Bacteria/classification , Bacteria/growth & development , Bacteria/isolation & purification , RNA, Ribosomal, 16S/genetics
16.
Diabetes Metab Syndr Obes ; 17: 981-995, 2024.
Article in English | MEDLINE | ID: mdl-38435630

ABSTRACT

Background: Obesity is a growing global problem that causes various complications such as diabetes, cognitive dysfunction, cardiovascular diseases, and hepatobiliary disease. Alpha-linolenic acid (ALA) has been reported to exhibit multiple pharmaceutical effects. This study aimed to explore the effects of ALA on obesity-induced adipose tissue accumulation, cognitive impairment, inflammation, and colonic mucosal barrier integrity. Methods: Mice were fed with high-fat diet (HFD) and were treated with ALA (60 or 100 mg/kg). Body weight, adipose tissue, serum glucose and lipid levels, glucose resistance, and insulin resistance were measured. Cognitive ability was analyzed using the behavior tests. PTP1B and IRS/p-AKT/p-GSK3ß/p-Tau signaling were examined to evaluate inflammation and synaptogenesis. Colon mucosal barrier integrity was examined by Alcian blue staining and expression of the tight junction proteins. The production of pro-inflammatory cytokines and liver damages were evaluated. 3T3-L1 cells were used for in vitro experiments. Cell viability, migration and invasion were detected. The levels of ROS, iron, and ferrous ions were measured to assess ferroptosis. Metabolomic analysis of adipose tissues was performed. Results: ALA treatment prevented HFD-induced adipose tissue accumulation, improved glucose and lipid homeostasis and metabolism. Administration of ALA repressed the HFD-induced increase in insulin levels and insulin resistance index. Serum and colon levels of pro-inflammatory cytokines were decreased after ALA treatment. ALA elevated mitochondrial content in brown adipose tissues. ALA ameliorated obesity-induced cognitive impairment and hippocampal inflammation, enhanced colon mucosa integrity. ALA treatment ameliorated HFD-induced liver damage and lipid accumulation and inhibited differentiation of preadipocyte 3T3-L1 cells into mature adipocytes and induces ferroptosis. Metabolomic analysis suggested that ALA may target the glycerolipid metabolism pathway to ameliorate obesity. Knockdown of AGPAT2 abolished the protective effects of ALA. Conclusion: ALA treatment suppressed adipose accumulation in adipocytes, improved cognitive ability and colon integrity, and alleviated liver damage by modulating the 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2).

17.
Cell Rep Med ; 5(3): 101450, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38508139

ABSTRACT

CD47 is a ligand of SIRPα, an inhibitory receptor expressed by macrophages, dendritic cells, and natural killer (NK) cells, and, therefore, transgenic overexpression of CD47 is considered an effective approach to inhibiting transplant rejection. However, the detrimental effect of CD47 signaling is overlooked when exploring this approach. Here, we construct a mutant CD47 by replacing the transmembrane and intracellular domains with a membrane anchor (CD47-IgV). In both human and mouse cells, CD47-IgV is efficiently expressed on the cell surface and protects against phagocytosis in vitro and in vivo but does not induce cell death or inhibit angiogenesis. Furthermore, hematopoietic stem cells expressing transgenic CD47-IgV show no detectable alterations in engraftment or differentiation. This study provides a potentially effective means of achieving transgenic CD47 expression that may help to produce gene-edited pigs for xenotransplantation and hypoimmunogenic pluripotent stem cells for regenerative medicine.


Subject(s)
Angiogenesis , CD47 Antigen , Animals , Humans , Mice , CD47 Antigen/genetics , CD47 Antigen/metabolism , Cell Death , Phagocytosis/genetics , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Swine
18.
Front Aging Neurosci ; 16: 1381692, 2024.
Article in English | MEDLINE | ID: mdl-38524118

ABSTRACT

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

19.
Nat Commun ; 15(1): 2489, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38509103

ABSTRACT

The elevation gradient has long been known to be vital in shaping the structure and function of terrestrial ecosystems, but little is known about the elevation-dependent pattern of net CO2 uptake, denoted by net ecosystem productivity (NEP). Here, by analyzing data from 203 eddy covariance sites across China, we report a negative linear elevation-dependent pattern of NEP, collectively shaped by varying hydrothermal factors, nutrient supply, and ecosystem types. Furthermore, the NEP shows a higher temperature sensitivity in high-elevation environments (3000-5000 m) compared with the lower-elevation environments (<3000 m). Model ensemble and satellite-based observations consistently reveal more rapid relative changes in NEP in high-elevation environments during the last four decades. Machine learning also predicts a stronger relative increase in high-elevation environments, whereas less change is expected at lower elevations. We therefore conclude a varying elevation-dependent pattern of the NEP of terrestrial ecosystems in China, although there is significant uncertainty involved.


Subject(s)
Carbon Dioxide , Ecosystem , Temperature , Hot Temperature , China
20.
BMC Psychol ; 12(1): 115, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429641

ABSTRACT

OBJECTIVE: To analyze factors influencing the service experience of magnetic resonance imaging (MRI) examination and psychological status of patients admitted to a hospital and propose targeted solutions, and optimize the examination process and nursing by analyzing the MRI examination experience and psychological effect on patients. METHODS: The MRI examination rooms of two tertiary general hospitals in Haikou City were sampled at random, and 206 patients who met the study criteria were surveyed on site. RESULTS: (1) The item with the lowest mean score for patient examination services was whether earplugs were provided to the patient during the examination (B8 = 0.47). (2) Environmental logistics experience (16.83 ± 3.036) received the lowest score among the three service experience dimensions. (3) The average anxiety score of the patients was 5.38. (4) There was a positive correlation between the examination experience and the examination service experience of the patients. (5) Patients with higher monthly income had decreased anxiety (coefficient = -2.334), and MRI examination of the extremities relieved the anxiety (coefficient = -4.782). CONCLUSION: The environmental logistics factors, poor service attitude, examination site, and income were the most significant factors affecting the MRI examination experience and psychological status of patients, which can be improved by providing information, enhancing the waiting environment, providing targeted patient education, and evaluating the experience immediately.


Subject(s)
Anxiety , Magnetic Resonance Imaging , Humans , Surveys and Questionnaires , Anxiety Disorders
SELECTION OF CITATIONS
SEARCH DETAIL
...