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1.
Clin Proteomics ; 21(1): 46, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951753

ABSTRACT

PURPOSE: The primary objective of this investigation is to systematically screen and identify differentially expressed proteins (DEPs) within the plasma of individuals afflicted with sepsis. This endeavor employs both Data-Independent Acquisition (DIA) and enzyme-linked immunosorbent assay (ELISA) methodologies. The overarching goal is to furnish accessible and precise serum biomarkers conducive to the diagnostic discernment of sepsis. METHOD: The study encompasses 53 sepsis patients admitted to the Affiliated Hospital of Southwest Medical University between January 2019 and December 2020, alongside a control cohort consisting of 16 individuals devoid of sepsis pathology. Subsequently, a subset comprising 10 randomly selected subjects from the control group and 22 from the sepsis group undergoes quantitative proteomic analysis via DIA. The acquired data undergoes Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses, facilitating the construction of a Protein-Protein Interaction (PPI) network to discern potential markers. Validation of core proteins is then accomplished through ELISA. Comparative analysis between the normal and sepsis groups ensues, characterized by Receiver Operating Characteristic (ROC) curve construction to evaluate diagnostic efficacy. RESULT: A total of 187 DEPs were identified through bioinformatic methodologies. Examination reveals their predominant involvement in biological processes such as wound healing, coagulation, and blood coagulation. Functional pathway analysis further elucidates their engagement in the complement pathway and malaria. Resistin emerges as a candidate plasma biomarker, subsequently validated through ELISA. Notably, the protein exhibits significantly elevated levels in the serum of sepsis patients compared to the normal control group. ROC curve analysis underscores the robust diagnostic capacity of these biomarkers for sepsis. CONCLUSION: Data-Independent Acquisition (DIA) and Enzyme-Linked Immunosorbent Assay (ELISA) show increased Resistin levels in sepsis patients, suggesting diagnostic potential, warranting further research.

2.
Nat Commun ; 15(1): 5705, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977710

ABSTRACT

In nature, coenzyme-independent oxidases have evolved in selective catalysis using isolated substrate-binding pockets. Single-atom nanozymes (SAzymes), an emerging type of non-protein artificial enzymes, are promising to simulate enzyme active centers, but owing to the lack of recognition sites, realizing substrate specificity is a formidable task. Here we report a metal-ligand dual-site SAzyme (Ni-DAB) that exhibited selectivity in uric acid (UA) oxidation. Ni-DAB mimics the dual-site catalytic mechanism of urate oxidase, in which the Ni metal center and the C atom in the ligand serve as the specific UA and O2 binding sites, respectively, characterized by synchrotron soft X-ray absorption spectroscopy, in situ near ambient pressure X-ray photoelectron spectroscopy, and isotope labeling. The theoretical calculations reveal the high catalytic specificity is derived from not only the delicate interaction between UA and the Ni center but also the complementary oxygen reduction at the beta C site in the ligand. As a potential application, a Ni-DAB-based biofuel cell using human urine is constructed. This work unlocks an approach of enzyme-like isolated dual sites in boosting the selectivity of non-protein artificial enzymes.


Subject(s)
Oxidation-Reduction , Urate Oxidase , Uric Acid , Substrate Specificity , Urate Oxidase/chemistry , Urate Oxidase/metabolism , Uric Acid/chemistry , Uric Acid/metabolism , Uric Acid/urine , Ligands , Humans , Nickel/chemistry , Nickel/metabolism , Binding Sites , Catalytic Domain , Catalysis , Models, Molecular , X-Ray Absorption Spectroscopy
3.
J Fungi (Basel) ; 10(6)2024 May 31.
Article in English | MEDLINE | ID: mdl-38921382

ABSTRACT

Sterigmatocystins and aflatoxins are a group of mycotoxins mainly isolated from fungi of the genera Aspergillus. Since the discovery of sterigmatocystins in 1954 and aflatoxins in 1961, many scholars have conducted a series of studies on their structural identification, synthesis and biological activities. Studies have shown that sterigmatocystins and aflatoxins have a wide range of biological activities such as antitumour, antibacterial, anti-inflammatory, antiplasmodial, etc. The sterigmatocystins and aflatoxins had been shown to be hepatotoxic and nephrotoxic in animals. This review attempts to give a comprehensive summary of progress on the chemical structural features, synthesis, and bioactivity of sterigmatocystins and aflatoxins reported from 1954 to April 2024. A total of 72 sterigmatocystins and 20 aflatoxins are presented in this review. This paper reviews the chemical diversity and potential activity and toxicity of sterigmatocystins and aflatoxins, enhances the understanding of sterigmatocystins and aflatoxins that adversely affect humans and animals, and provides ideas for their prevention, research and development.

4.
Int J Mol Sci ; 25(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38928141

ABSTRACT

Unlike sedentary plant-parasitic nematodes, migratory plant endoparasitic nematodes (MPENs) are unable to establish permanent feeding sites, and all developmental stages (except eggs) can invade and feed on plant tissues and can be easily overlooked because of the unspecific symptoms. They cause numerous economic losses in agriculture, forestry, and horticulture. In order to understand the pathogenetic mechanism of MPENs, here we describe research on functions and host targets focused on currently identified effectors from six MPENs, namely Radopholus similis, Pratylenchus spp., Ditylenchus destructor, Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Hirschmanniella oryzae. This information will provide valuable insights into understanding MPEN effectors and for future fostering advancements in plant protection.


Subject(s)
Host-Parasite Interactions , Plant Diseases , Plants , Animals , Plant Diseases/parasitology , Plants/parasitology , Nematoda/pathogenicity , Helminth Proteins/metabolism
5.
Sci Rep ; 14(1): 13831, 2024 06 15.
Article in English | MEDLINE | ID: mdl-38879647

ABSTRACT

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1, as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.


Subject(s)
Cell Differentiation , Endothelial Cells , Induced Pluripotent Stem Cells , Liver , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Endothelial Cells/metabolism , Endothelial Cells/cytology , Liver/metabolism , Liver/cytology , Single-Cell Analysis/methods , Cells, Cultured , Biomarkers/metabolism , Lipoproteins, LDL/metabolism , Gene Expression Profiling
6.
Article in English | MEDLINE | ID: mdl-38871958

ABSTRACT

BACKGROUND: The importance of building ventilation to protect health has been more widely recognized since the COVID-19 pandemic. Outdoor air ventilation in buildings dilutes indoor-generated air pollutants (including bioaerosols) and reduces resulting occupant exposures. Many countries and organizations have advisory guidelines or mandatory standards for minimum ventilation rates (VRs) to maintain indoor air quality (IAQ). Because directly measuring VRs is often difficult, many IAQ guidelines instead specify indoor concentration limits for carbon dioxide (CO2), using CO2 exhaled by building occupants as an indicator of VR. Although indoor CO2 guidelines are common, the evidence basis for the various CO2 limits has not been clear. OBJECTIVE: To review current indoor CO2 guidelines worldwide and the supportive evidence provided. METHODS: We identified worldwide CO2-based guidelines for IAQ or ventilation, along with any supportive evidence provided. We excluded occupational guidelines for CO2 levels ≥5000 ppm. RESULTS: Among 43 guidelines identified, 35 set single CO2 concentration limits and eight set multi-tiered limits; 16 mentioned no specific human effect to be controlled, 19 specified only odor dissatisfaction, five specified non-infectious health effects, and three specified airborne infectious disease transmission. The most common indoor CO2 limit was 1000 ppm. Thirteen guidelines specified maximum CO2 limits as extended time-weighted averages, none with evidence linking averaged limits to occupant effects. Of only 18 guidelines citing evidence to support limits set, we found this evidence persuasive for eight. Among these eight guidelines, seven set limits to control odor perception. One provided 17 scientifically-based CO2 limits, for specific example space uses and occupancies, to control long-range COVID-19 transmission indoors. IMPACT: Many current indoor carbon dioxide (CO2) guidelines for indoor air quality specified no adverse effects intended for control. Odor dissatisfaction was the effect mentioned most frequently, few mentioned health, and three mentioned control of infectious disease. Only one CO2 guideline was developed from scientific models to control airborne transmission of COVID-19. Most guidelines provided no supportive evidence for specified limits; few provided persuasive evidence. No scientific basis is apparent for setting one CO2 limit for IAQ across all buildings, setting a CO2 limit for IAQ as an extended time-weighted average, or using a one-time CO2 measurement to verify a desired VR.

7.
FASEB J ; 38(10): e23646, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38795328

ABSTRACT

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-ß-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3ß/ß-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.


Subject(s)
Chaperone-Mediated Autophagy , Glycogen Synthase Kinase 3 beta , Inflammation , Lysosomal-Associated Membrane Protein 2 , Mesenchymal Stem Cells , Osteogenesis , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , beta Catenin , Animals , Osteogenesis/physiology , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Proto-Oncogene Proteins c-akt/metabolism , Mice , Phosphatidylinositol 3-Kinases/metabolism , beta Catenin/metabolism , Humans , Mesenchymal Stem Cells/metabolism , Inflammation/metabolism , Lysosomal-Associated Membrane Protein 2/metabolism , Lysosomal-Associated Membrane Protein 2/genetics , Signal Transduction , Male , Mice, Inbred C57BL , Osteoblasts/metabolism , Cell Differentiation , Osteoclasts/metabolism
8.
J Colloid Interface Sci ; 671: 553-563, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38820840

ABSTRACT

Recently, the solar-driven interfacial evaporation desalination has attracted more and more attentions due to the advantages of low cost, zero energy consumption, and high water purification rate, etc. One of the bottlenecks of this emerging technique lies in a lack of simple and low-cost ways to construct three-dimensional (3D) hierarchical microstructures for photothermal membranes. To this end, a two-step strategy is carried out by combining surface functionalization with substrate engineering. Firstly, a silane coupling agent 3-aminopropyltriethoxysilane (APTES) is grafted onto an ideal photothermal material of Ti3C2Tx MXene, to improve the nanochannel sizes and hydrophilicity, which are attributed to enlarged interspaces of MXene and introduced hydrophilic group e.g., -NH2 and -OH, respectively. Secondly, a low-cost and robust nonwoven fiber (NWF) substrate, which has a 3D micron-sized mesh structure with interlaced fiber stacks, is employed as the skeleton to load enough APTES-grafted MXene by a simple soaking method. Benefited from above design, the Ti3C2Tx-APTES/NWF composite membrane with a 3D hierarchical structure shows enhanced light scattering and utilization, water transport and vapor escape. A remarkable evaporation rate of 1.457 kg m-2 h-1 and an evaporation efficiency of 91.48 % are attained for a large-area (5 × 5 cm2) evaporator, and the evaporation rate is further increased to 1.672 kg m-2 h-1 for a small-area (2 × 2 cm2) device. The rejection rates of salt ions and heavy metal ions are higher than 99 % and 99.99 %, respectively, and the removal rates of organic dye molecules are nearly to 100 %. Besides, the composite photothermal membrane exhibits great stabilities in harsh conditions such as high salinities, long cycling, large light intensities, strong acid/alkali environments, and mechanical bending. Most importantly, the photothermal membrane shows a considerable cost-effectiveness of 89.4 g h-1/$. Hence, this study might promote the commercialization of solar-driven interfacial evaporation desalination by collaboratively considering surface modification and substrate engineering for MXene.

9.
Chemphyschem ; : e202400290, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695835

ABSTRACT

Dye-sensitized solar cells (DSSCs), quantum dot-sensitized solar cells (QDSSCs) and perovskite solar cells (PSCs) have attracted wide attention. DSSCs, QDSSCs and PSCs can be prepared by liquid phase or solid phase, which causes a certain range of interface micro-mass changes during preparation. In addition, the photoelectric conversion process occurring inside the device also inevitably causes interface micro-mass changes. Interpretation of these interface micro-mass changes can help to optimize the cell structure, improve the stability and performance repeatability of the device, as well as directly or indirectly infer, track and predict the internal photoelectric conversion mechanism of the device. Quartz crystal microbalance (QCM) is a powerful tool for studying surface mass changes, extending this technology to the fields of solar cells to directly obtain interface micro-mass changes, which makes the research more in-depth and opens up a new perspective for explaining the basic principles of solar cells. This review summarizes the research progress of QCM application in DSSCs, QDSSCs and PSCs in recent years, and explores the challenges and new opportunities of QCM application in new solar cells in the future.

10.
Research (Wash D C) ; 7: 0355, 2024.
Article in English | MEDLINE | ID: mdl-38694202

ABSTRACT

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

11.
Chem Commun (Camb) ; 60(45): 5828-5831, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38747249

ABSTRACT

The salt metathesis of a boryl-ethynyl lithium salt {[(HCDipN)2]B-CC-Li} with a monochlorosilylene [LSi(:)Cl; L = PhC(NtBu)2] produced an isolable boryl-ethynyl silylene {1; [(HCDipN)2]B-CC-Si(L)}. The Si(II) center in 1 possesses a nonbonding lone pair and forms a covalent bond with the ethynyl group. The characterization of 1 was carried out by multinuclear NMR spectroscopy, single-crystal X-ray structure analysis and DFT calculations. Additionally, a reactivity study of 1 was conducted towards oxygen-containing and aryl C-F substrates.

12.
Mol Immunol ; 170: 110-118, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38653076

ABSTRACT

Sepsis is a systemic inflammatory response syndrome caused by trauma or infection, which can lead to multiple organ dysfunction. In severe cases, sepsis can also progress to septic shock and even death. Effective treatments for sepsis are still under development. This study aimed to determine if targeting the PI3K/Akt signaling with CAL-101, a PI3K p110δ inhibitor, could alleviate lipopolysaccharide (LPS)-induced sepsis and contribute to immune tolerance. Our findings indicated that CAL-101 treatment improved survival rates and alleviated the progression of LPS-induced sepsis. Compared to antibiotics, CAL-101 not only restored the Th17/regulatory T cells (Treg) balance but also enhanced Treg cell function. Additionally, CAL-101 promoted type 2 macrophage (M2) polarization, inhibited TNF-α secretion, and increased IL-10 secretion. Moreover, CAL-101 treatment reduced pyroptosis in peritoneal macrophages by inhibiting caspase-1/gasdermin D (GSDMD) activation. This study provides a mechanistic basis for future clinical exploration of targeted therapeutics and immunomodulatory strategies in the treatment of sepsis.


Subject(s)
Class I Phosphatidylinositol 3-Kinases , Mice, Inbred C57BL , Pyroptosis , Sepsis , T-Lymphocytes, Regulatory , Th17 Cells , Animals , Mice , Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Class I Phosphatidylinositol 3-Kinases/metabolism , Macrophages/immunology , Macrophages/drug effects , Macrophages/metabolism , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/metabolism , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Pyroptosis/drug effects , Sepsis/immunology , Sepsis/drug therapy , Signal Transduction/drug effects , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/drug effects , Th17 Cells/immunology , Th17 Cells/drug effects
13.
ACS Omega ; 9(15): 17028-17035, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38645333

ABSTRACT

Gluten is a well-known food allergen globally, and it can induce immune responses in celiac- and nonceliac gluten-sensitive patients. The gliadin proteins from gluten have a special amino acid sequence that make it hydrophobic. One way to deal with gluten allergies is to provide a gluten-free diet. The hydrophobic characteristic of gliadin makes gliadin detection more difficult. An analyst needs to use an organic solvent or multiple processes to denature gluten for extraction. Although organic solvents can rapidly extract gluten in a sample, organic solvent also denatures the antibody and induces false biotest results without buffer dilute, and the accuracy will reduce with buffer dilute. An ionic liquid (IL) is a highly modifiable green chemical organic salt. The imidazolium has a cationic structure and is modified with different lengths (C = 0, 1, 3, 5, 7, 9, and 12) of carbon side chains with organic and inorganic anions [methanesulfonate (MSO), Cl-, F-, NO3-, HSO4-, and H2PO4-] to make different kinds of ILs for testing the solubility of gliadin. Different IL/water ratios were used to test the solubility of gluten. We measured the solubility of gliadin in different imidazolium ILs, and the kinetic curve of gliadin dissolved in 1% [C5DMIM][MSO]aq was conducted. We also used circular dichroism spectroscopy and an enzyme-linked immunosorbent assay to measure the gliadin structure and the effect of binding with an antibody after 1% [C5DMIM][MSO]aq treatment. An 2,3-bis-(2-methoxy-4- nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay was used to test the toxicity of [C5DMIM][MSO]aq in N2a cells. In our research, 1% [C5DMIM][MSO]aq produced a good solubility of gluten, and it could dissolve more than 3000 ppm of gluten in 5 min. [C5DMIM][MSO]aq did not break down the gluten structure and did not restrict antibody binding to gluten, and more importantly, [C5DMIM][MSO] did not exhibit cell toxicity. In this report, we showed that [C5DMIM][MSO] could be a good extraction solution applied for gluten detection.

14.
Phytomedicine ; 129: 155567, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38579644

ABSTRACT

BACKGROUND: Sarcopenia, an age-related disease, is characterized by a gradual loss of muscle mass, strength, and function. It has been linked to abnormal organelle function in myotubes, including the mitochondria and endoplasmic reticulum (ER). Recent studies revealed that mitochondria-associated membranes (MAM), the sites connecting mitochondria and the ER, may be implicated in skeletal muscle aging. In this arena, the potential of Polygonatum sibiricum polysaccharide (PSP) emerges as a beacon of hope. PSP, with its remarkable antioxidant and anti-senescence properties, is on the cusp of a therapeutic revolution, offering a promising strategy to mitigate the impacts of sarcopenia. PURPOSE: The objective of this research is to explore the effects of PSP on age-related muscle dysfunction and the underlying mechanisms involved both in vivo and in vitro. METHODS: In this investigation, we used in vitro experiments using D-galactose (D-gal)-induced aging in C2C12 myotubes and in vivo experiments on aged mice. Key indices were assessed, including reactive oxygen species (ROS) levels, mitochondrial function, the expression of aging-related markers, and the key proteins of mitochondria and MAM fraction. Differentially expressed genes (DEGs) related to mitochondria and ER were identified, and bioinformatic analyses were performed to explore underlying mechanisms. Muscle mass and function were determined to evaluate the quantity and quality of skeletal muscle in vivo. RESULTS: PSP treatment effectively mitigated oxidative stress and mitochondrial malfunction caused by D-gal in C2C12 myotubes, preserving mitochondrial fitness and reducing MAM formation. Besides, PSP attenuated D-gal-induced increases in Ca2+ concentrations intracellularly by modulating the calcium-related proteins, which were also confirmed by gene ontology (GO) analysis of DEGs. In aged mice, PSP increased muscle mass and improved grip strength, hanging time, and other parameters while reducing ROS levels and increasing antioxidant enzyme activities in skeletal muscle tissue. CONCLUSION: PSP offers protection against age-associated muscle impairments. The proposed mechanism suggests that modulation of calcium homeostasis via regulation of the MAM results in a favorable functional outcome during skeletal muscle aging. The results of this study highlight the prospect of PSP as a curative intervention for sarcopenia and affiliated pathological conditions, warranting further investigation.


Subject(s)
Aging , Calcium , Homeostasis , Muscle, Skeletal , Polygonatum , Polysaccharides , Reactive Oxygen Species , Animals , Polysaccharides/pharmacology , Polygonatum/chemistry , Mice , Homeostasis/drug effects , Reactive Oxygen Species/metabolism , Calcium/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Aging/drug effects , Male , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Sarcopenia/drug therapy , Mitochondrial Membranes/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Cell Line , Mice, Inbred C57BL , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Antioxidants/pharmacology , Mitochondria Associated Membranes
15.
Sci Immunol ; 9(94): eadh0085, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38669317

ABSTRACT

Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)-mediated ablation of PD-1+ cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1-specific depleting antibodies, we found that antibody-mediated depletion of PD-1+ cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.


Subject(s)
Clonal Deletion , Immune Tolerance , Mice, Inbred C57BL , Programmed Cell Death 1 Receptor , Animals , Programmed Cell Death 1 Receptor/immunology , Mice , Clonal Deletion/immunology , Immune Tolerance/immunology , Humans , Encephalomyelitis, Autoimmune, Experimental/immunology , Heart Transplantation , T-Lymphocytes/immunology , Mice, Knockout , Mice, Inbred BALB C , Female
16.
Sci Rep ; 14(1): 9676, 2024 04 27.
Article in English | MEDLINE | ID: mdl-38678059

ABSTRACT

To utilize metabolomics in conjunction with RNA sequencing to identify biomarkers in the blood of sepsis patients and discover novel targets for diagnosing and treating sepsis. In January 2019 and December 2020, blood samples were collected from a cohort of 16 patients diagnosed with sepsis and 11 patients diagnosed with systemic inflammatory response syndrome (SIRS). Non-targeted metabolomics analysis was conducted using liquid chromatography coupled with mass spectrometry (LC-MS/MS technology), while gene sequencing was performed using RNA sequencing. Afterward, the metabolite data and sequencing data underwent quality control and difference analysis, with a fold change (FC) greater than or equal to 2 and a false discovery rate (FDR) less than 0.05.Co-analysis was then performed to identify differential factors with consistent expression trends based on the metabolic pathway context; KEGG enrichment analysis was performed on the crossover factors, and Meta-analysis of the targets was performed at the transcriptome level using the public dataset. In the end, a total of five samples of single nucleated cells from peripheral blood (two normal controls, one with systemic inflammatory response syndrome, and two with sepsis) were collected and examined to determine the cellular location of the essential genes using 10× single cell RNA sequencing (scRNA-seq). A total of 485 genes and 1083 metabolites were found to be differentially expressed in the sepsis group compared to the SIRS group. Among these, 40 genes were found to be differentially expressed in both the metabolome and transcriptome. Functional enrichment analysis revealed that these genes were primarily involved in biological processes related to inflammatory response, immune regulation, and amino acid metabolism. Furthermore, a meta-analysis identified four genes, namely ITGAM, CD44, C3AR1, and IL2RG, which were highly expressed in the sepsis group compared to the normal group (P < 0.05). Additionally, scRNA-seq analysis revealed that the core genes ITGAM and C3AR1 were predominantly localized within the macrophage lineage. The primary genes ITGAM and C3AR1 exhibit predominant expression in macrophages, which play a significant role in inflammatory and immune responses. Moreover, these genes show elevated expression levels in the plasma of individuals with sepsis, indicating their potential as valuable subjects for further research in sepsis.


Subject(s)
Biomarkers , Metabolomics , Sepsis , Humans , Sepsis/genetics , Sepsis/blood , Sepsis/metabolism , Biomarkers/blood , Metabolomics/methods , Male , Female , Middle Aged , Transcriptome , Gene Expression Profiling , Aged , Adult , Chromatography, Liquid , Tandem Mass Spectrometry , Systemic Inflammatory Response Syndrome/genetics , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/metabolism , Systemic Inflammatory Response Syndrome/diagnosis
17.
BMC Musculoskelet Disord ; 25(1): 338, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671421

ABSTRACT

OBJECTIVES: The application of a growing rod technique can retain the growth and development potential of the spine and thorax while controlling the progression of scoliosis deformity. Theoretically, convex side short fusion combined with a concave side single growing rod technique can significantly reduce the asymmetric growth of the spine in the vertex region in most patients. However, the final clinical outcome of various techniques is yet to be clearly determined and compared between studies. Therefore, we compared the efficacy of these two growing rod techniques in treating early onset scoliosis. METHODS: In a retrospective study of 152 EOS patients seen between 2013.1 and 2019.12, 36 cases of EOS patients were selected for inclusion. Among the 36 cases, 11 cases were treated with convex side short fusion combined with a concave side single growing rod technique, group (A) The remaining 25 cases were treated with traditional bilateral growing rod technique, group (B) Age, gender, etiology, follow-up time, Cobb angle of main curve, T1-S1 height, coronal trunk shift, sagittal vertical axis (SVA), Cobb angle of thoracic kyphosis at last follow-up, and Cobb angle at proximal junction kyphosis of the first and last post-operation follow-up were recorded. In addition, internal fixation related complications, infection, nervous system complications were recorded as well. RESULTS: There was no statistically significant difference between group A and group B in preoperative age, Cobb angle of main curve, coronal trunk shift, T1-S1 height, SVA, Cobb angle of thoracic kyphosis (p > 0.05). However, at the last follow-up (Group A, mean 4.4 ± 1.01 years; Group B, mean 3.6 ± 0.01 years) the Cobb angle of the main curve was less and T1-S1 height greater in group A compared with group B (p < 0.05). There was no statistically significant difference between group A and group B in the correction rate of the Cobb angle of the main curve or the growth rate of T1-S1 height (p > 0.05). There was no statistically significant difference in the coronal imbalance ratio, thoracic kyphosis abnormality ratio, or the occurrence PJK ratio between group A and group B at the last follow-up (p > 0.05), but the sagittal imbalance ratio and internal fixation abnormality ratio were higher in group A than in the group B (p < 0.05). CONCLUSIONS: During the treatment of EOS, both the convex side short fusion combined with concave side single growing rod technique and traditional bilateral growing rod technique can correct the Cobb angle of main curve with no significant hindering of the spinal growth observed. The traditional bilateral growing rod technique has advantages in control of the sagittal balance of the spine, and the complications associated with internal fixation were lower.


Subject(s)
Scoliosis , Spinal Fusion , Humans , Scoliosis/surgery , Scoliosis/diagnostic imaging , Female , Retrospective Studies , Male , Spinal Fusion/methods , Spinal Fusion/adverse effects , Spinal Fusion/instrumentation , Child , Treatment Outcome , Thoracic Vertebrae/surgery , Thoracic Vertebrae/diagnostic imaging , Child, Preschool , Follow-Up Studies , Age of Onset
18.
J Am Chem Soc ; 146(17): 12215-12224, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38629769

ABSTRACT

We report the construction of frustrated Lewis pairs (FLPs) in a metal-organic framework (MOF), where both Lewis acid (LA) and Lewis base (LB) are fixed to the backbone. The anchoring of a tritopic organoboron linker as LA and a monotopic linker as LB to separate metal oxide clusters in a tetrahedron geometry allows for the precise control of distance between them. As the type of monotopic LB linker varies, pyridine, phenol, aniline, and benzyl alcohol, a series of 11 FLPs were constructed to give fixed distances of 7.1, 5.5, 5.4, and 4.8 Å, respectively, revealed by 11B-1H solid-state nuclear magnetic resonance spectroscopy. Keeping LA and LB apart by a fixed distance makes it possible to investigate the electrostatic effect by changing the functional groups in the monotopic LB linker, while the LA counterpart remains unaffected. This approach offers new chemical environments of the active site for FLP-induced catalysis.

19.
Aquat Toxicol ; 271: 106928, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38688065

ABSTRACT

The significant role of aquatic phytoplankton in global primary productivity, accounting for approximately 50 % on an annual basis, has been recognized as a crucial factor in the reduction of Hg(II). In this study, we compared the efficiency of Hg(II) photoreduction mediated by three types of algae leaching dissolved organic matter (DOM) and humic acid (DOM-HA). Especially, we investigated the potential effects of algae-leached DOM on the photoreduction of Hg(II) and its subsequent uptake by lettuce, which serves as an indicator of Hg bioavailability for aquatic plants. The results revealed that under light conditions, the conversion of Hg(II) to Hg(0) mediated by algae-leached DOM and DOM-HA was 6.4-39.9 % higher compared to dark condition. Furthermore, the free radical quenching experiment demonstrated that the reduction of Hg(II) mediated by DOM-HA was higher than algae-leached DOM, mainly due to its ability to generate superoxide anion (O2•-). Moreover, the photoreduction efficiences of Hg(II) mediated by algae-leached DOM were 29-18 % lower compared to DOM-HA. The FT-IR analysis revealed that the production of -SH from algae-leached DOM led to the formation of strong metal-complexes, which restricts the reduction process from Hg(II) to Hg(0). Finally, the hydroponics experiment demonstrated that algae-leached DOM inhibited the bioavailability of Hg(II) to plants more effectively than DOM-HA. Our research emphasizes the significant functional roles and potential mechanisms of algae in reducing Hg levels, thereby influencing the availability of Hg in aquatic ecosystems.


Subject(s)
Humic Substances , Lactuca , Light , Mercury , Water Pollutants, Chemical , Lactuca/metabolism , Lactuca/radiation effects , Oxidation-Reduction
20.
IEEE Trans Med Imaging ; PP2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38557622

ABSTRACT

Ophthalmic diseases such as central serous chorioretinopathy (CSC) significantly impair the vision of millions of people globally. Precise segmentation of choroid and macular edema is critical for diagnosing and treating these conditions. However, existing 3D medical image segmentation methods often fall short due to the heterogeneous nature and blurry features of these conditions, compounded by medical image clarity issues and noise interference arising from equipment and environmental limitations. To address these challenges, we propose the Spectrum Analysis Synergy Axial-Spatial Network (SASAN), an approach that innovatively integrates spectrum features using the Fast Fourier Transform (FFT). SASAN incorporates two key modules: the Frequency Integrated Neural Enhancer (FINE), which mitigates noise interference, and the Axial-Spatial Elementum Multiplier (ASEM), which enhances feature extraction. Additionally, we introduce the Self-Adaptive Multi-Aspect Loss (LSM), which balances image regions, distribution, and boundaries, adaptively updating weights during training. We compiled and meticulously annotated the Choroid and Macular Edema OCT Mega Dataset (CMED-18k), currently the world's largest dataset of its kind. Comparative analysis against 13 baselines shows our method surpasses these benchmarks, achieving the highest Dice scores and lowest HD95 in the CMED and OIMHS datasets. Our code is publicly available at https://github.com/IMOP-lab/SASAN-Pytorch.

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