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1.
Plant Cell ; 36(10): 4388-4403, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-38917216

ABSTRACT

Plants generally enhance their root growth in the form of greater biomass and/or root length to boost nutrient uptake in response to short-term low nitrogen (LN). However, the underlying mechanisms of short-term LN-mediated root growth remain largely elusive. Our genome-wide association study, haplotype analysis, and phenotyping of transgenic plants showed that the crucial nitrate signaling component NIN-LIKE PROTEIN3.2 (ZmNLP3.2), a positive regulator of root biomass, is associated with natural variations in root biomass of maize (Zea mays L.) seedlings under LN. The monocot-specific gene AUXIN/INDOLE-3-ACETIC ACID14 (ZmAux/IAA14) exhibited opposite expression patterns to ZmNLP3.2 in ZmNLP3.2 knockout and overexpression lines, suggesting that ZmNLP3.2 hampers ZmAux/IAA14 transcription. Importantly, ZmAux/IAA14 knockout seedlings showed a greater root dry weight (RDW), whereas ZmAux/IAA14 overexpression reduced RDW under LN compared with wild-type plants, indicating that ZmAux/IAA14 negatively regulates the RDW of LN-grown seedlings. Moreover, in vitro and vivo assays indicated that AUXIN RESPONSE FACTOR19 (ZmARF19) binds to and transcriptionally activates ZmAux/IAA14, which was weakened by the ZmNLP3.2-ZmARF19 interaction. The zmnlp3.2 ZmAux/IAA14-OE seedlings exhibited further reduced RDW compared with ZmAux/IAA14 overexpression lines when subjected to LN treatment, corroborating the ZmNLP3.2-ZmAux/IAA14 interaction. Thus, our study reveals a ZmNLP3.2-ZmARF19-ZmAux/IAA14 module regulating root biomass in response to nitrogen limitation in maize.


Subject(s)
Biomass , Gene Expression Regulation, Plant , Nitrogen , Plant Proteins , Plant Roots , Seedlings , Zea mays , Zea mays/genetics , Zea mays/metabolism , Zea mays/growth & development , Nitrogen/metabolism , Seedlings/genetics , Seedlings/growth & development , Seedlings/metabolism , Plant Roots/growth & development , Plant Roots/metabolism , Plant Roots/genetics , Plant Proteins/metabolism , Plant Proteins/genetics , Plants, Genetically Modified , Indoleacetic Acids/metabolism , Genome-Wide Association Study
2.
J Infect Dis ; 229(1): 252-261, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-37882788

ABSTRACT

BACKGROUND: Delayed diagnosis and improper therapy for intraocular infections usually result in poor prognosis. Due to limitations of conventional culture and polymerase chain reaction methods, most causative pathogens cannot be identified from vitreous humor (VH) or aqueous humor (AH) samples with limited volume. METHODS: Patients with suspected intraocular infections were enrolled from January 2019 to August 2021. Metagenomic next-generation sequencing (mNGS) was used to detected causative pathogens. RESULTS: This multicenter prospective study enrolled 488 patients, from whom VH (152) and AH (336) samples were respectively collected and analyzed using mNGS of cell-free DNA (cfDNA). Taking final comprehensive clinical diagnosis as the gold standard, there were 39 patients with indefinite final diagnoses, whereas 288 and 161 patients were diagnosed as definite infectious and noninfectious diseases, respectively. Based on clinical adjudication, the sensitivity (92.2%) and total coincidence rate (81.3%) of mNGS using VH samples were slightly higher than those of mNGS using AH samples (85.4% and 75.4%, respectively). CONCLUSIONS: Using mNGS of cfDNA, an era with clinical experience for more rapid, independent, and impartial diagnosis of bacterial and other intraocular infections can be expected.


Subject(s)
Cell-Free Nucleic Acids , Eye Infections , Humans , Aqueous Humor , Cell-Free Nucleic Acids/genetics , Prospective Studies , High-Throughput Nucleotide Sequencing , Metagenomics , Sensitivity and Specificity
3.
Anal Chem ; 96(37): 14877-14883, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39219057

ABSTRACT

Greenhouse gas (GHG) detection plays an important role in climate change research and industry applications. A novel photoacoustic spectroscopy (PAS) sensor based on multiple resonators has been developed for the detection of GHGs. The major GHGs CO2, CH4, and N2O were measured simultaneously using only one acoustic sensor by coupling three acoustic resonators into a photoacoustic cell. A sinusoidal voltage signal-driven noise source was integrated into a multiresonator photoacoustic cell, allowing convenient calibration of the resonant frequency of the photoacoustic cell. The performance of the sensor was further enhanced by reflecting a laser beam four times in the photoacoustic cell. Allan deviation analysis showed that the minimum detection limits of 2.7 ppm, 90 ppb, and 1 ppb could be achieved for CO2, CH4, and N2O, respectively, over a 300 s integration time. The feasibility of the system was confirmed by continuous measurements of the three major GHGs from different sources for up to 10 h.

4.
New Phytol ; 243(4): 1424-1439, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38922886

ABSTRACT

Acyl-CoA-Binding Proteins (ACBPs) bind acyl-CoA esters and function in lipid metabolism. Although acbp3-1, the ACBP3 mutant in Arabidopsis thaliana ecotype Col-0, displays normal floral development, the acbp3-2 mutant from ecotype Ler-0 characterized herein exhibits defective adaxial anther lobes and improper sporocyte formation. To understand these differences and identify the role of ERECTA in ACBP3 function, the acbp3 mutants and acbp3-erecta (er) lines were analyzed by microscopy for anther morphology and high-performance liquid chromatography for lipid composition. Defects in Landsberg anther development were related to the ERECTA-mediated pathway because the progenies of acbp3-2 × La-0 and acbp3-1 × er-1 in Col-0 showed normal anthers, contrasting to that of acbp3-2 in Ler-0. Polymorphism in the regulatory region of ACBP3 enabled its function in anther development in Ler-0 but not Col-0 which harbored an AT-repeat insertion. ACBP3 expression and anther development in acbp3-2 were restored using ACBP3pro (Ler)::ACBP3 not ACBP3pro (Col)::ACBP3. SPOROCYTELESS (SPL), a sporocyte formation regulator activated ACBP3 transcription in Ler-0 but not Col-0. For anther development, the ERECTA-related role of ACBP3 is required in Ler-0, but not Col-0. The disrupted promoter regulatory region for SPL binding in Col-0 eliminates the role of ACBP3 in anther development.


Subject(s)
Alleles , Arabidopsis Proteins , Arabidopsis , Flowers , Gene Expression Regulation, Plant , Promoter Regions, Genetic , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Diazepam Binding Inhibitor/metabolism , Diazepam Binding Inhibitor/genetics , Ecotype , Flowers/genetics , Flowers/growth & development , Mutation/genetics , Phenotype , Polymorphism, Genetic , Promoter Regions, Genetic/genetics
5.
Article in English | MEDLINE | ID: mdl-39180420

ABSTRACT

OBJECTIVE: Osteoarthritis (OA) is a chronic disease characterized by cartilage degeneration and inflammation, with no approved disease-modifying drugs. This study aimed to identify pathogenic genes and elucidate their mechanism in OA. METHODS: We systematically identified pathogenic genes combined sing-cell and bulk transcriptome profiles of cartilage tissues in OA. Adenovirus carrying the serpin peptidase inhibitor clade E member 2 (serpinE2) or exogenous serpinE2 was injected into monosodium iodoacetate (MIA)-induced OA-model rats. Histological analysis, immunohistochemistry, and Alcian blue staining were performed. In vitro, immunofluorescence, quantitative real-time PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot assays were performed. RESULTS: SerpinE2 exhibited elevated expression and hypomethylation, showing a positive association with collagen pathway activities in patients with OA. Silencing serpinE2 aggravated MIA-induced knee cartilage degeneration in OA-model rats. Conversely, the intra-articular injection of exogenous serpinE2 ameliorated articular cartilage degeneration, reduced pain-related behavioral responses, and relieve synovitis in MIA-induced OA-model rats. Exogenous serpinE2 not only attenuated the elevation of NLRP3, IL-1ß, and caspase1 expression levels but also restored the reduction in cell viability induced by lipopolysaccharide (LPS) in chondrocytes. Mechanistically, we found that exogenous serpinE2 inhibited LPS-induced reactive oxygen species (ROS) release and NF-κB signalling activation. CONCLUSIONS: SerpinE2 plays a protective role in cartilage and synovium tissues, suggesting that serpinE2 gene transfer or molecules that upregulate serpinE2 expression could be therapeutic candidates for OA.

6.
Opt Lett ; 49(4): 1033-1036, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38359246

ABSTRACT

Pressure is an important parameter in assessing combustion performance that is typically measured using contact sensors. However, contact sensors usually disturb combustion flows and suffer from the temperature tolerance limit of sensor materials. In this Letter, an innovative noncontact two-color pressure sensing method based on tunable diode laser absorption spectroscopy (TDLAS) is proposed. This makes it possible to measure pressure at high temperature environments for combustion diagnostics. The proposed method uses the linear combination of the collision-broadened linewidths of two H2O absorption lines near 1343 and 1392 nm to measure the pressure. The feasibility and performance of such method have been demonstrated by measuring pressures from 1 to 5 bars at temperatures up to 1300 K with a laser wavelength scanning rate of 20 kHz. Measurement errors were found to be within 3%. Compared to previously reported TDLAS pressure sensors, this method is free from the influence of concentration and can also be combined with the existing two-color TDLAS thermometry to realize a fast, on line, and multi-parameter measurement in combustion diagnostics.

7.
Bioorg Med Chem ; 114: 117961, 2024 Oct 18.
Article in English | MEDLINE | ID: mdl-39437535

ABSTRACT

A series of 2,4-disubstituted-oxazole derivatives have been designed and synthesized based on compound 3a, a promising lead compound developed in our lab. Among these derivatives, the optimized compound 5k exhibited potent hypoglycemic activity, increasing glucose consumption by 60 % in HepG2 cells compared to the solvent control, and its activity was higher than that of metformin. Further investigation indicated that compound 5k exhibited negligible cytotoxic effects at a concentration of 25 µM in HepG2 and 3T3-L1 cells and showed moderate inhibitory activity against various subtypes of human cytochrome P450 subtypes. An oral glucose tolerance test confirmed that 5k is an effective hypoglycemic agent. Additionally, mechanistic studies suggested that 5k may exert its hypoglycemic activity through the activation of the AMPK pathway.

8.
Environ Res ; 241: 117612, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37951380

ABSTRACT

This study systematically investigated the variable main electrooxidation mechanism of chlorophene (CP) and dichlorophen (DCP) with the change of reaction conditions at Ti4O7 anode operated in batch and reactive electrochemical membrane (REM) modes. Significant degradation of CP and DCP was observed, that is, CP exhibited greater removal efficiency in batch mode at 0.5-3.5 mA cm-2 and REM operation (0.5 mA cm-2) with a permeate flow rate of 0.85 cm min-1 under the same reaction conditions, while DCP exhibited a faster degradation rate with the increase of current density in REM operation. Density functional theory (DFT) simulation and electrochemical performance tests indicated that the electrooxidation efficiency of CP and DCP in batch mode was primarily affected by the mass transfer rates. And the removal efficiency when anodic potentials were less than 1.7 V vs SHE in REM operation was determined by the activation energy for direct electron transfer (DET) reaction, however, the adsorption function of CP and DCP on the Ti4O7 anode became a dominant factor in determining the degradation efficiency with the further increase of anodic potential due to the disappeared activation barrier. In addition, the degradation pathways of CP and DCP were proposed according to intermediate products identification and frontier electron densities (FEDs) calculation, the acute toxicity of CP and DCP were also effectively decreased during both batch and REM operations.


Subject(s)
Dichlorophen , Water Pollutants, Chemical , Adsorption , Oxidation-Reduction
9.
Dig Dis Sci ; 69(6): 2123-2131, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38609542

ABSTRACT

BACKGROUND: The incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) is increasing. Although the guideline defines the diagnostic criteria as triglyceride (TG) greater than 11.3 mmol/L, there is actually no specific threshold. Many people with hypertriglyceridemia (HTG) or obvious chyloid blood do not develop acute pancreatitis (AP). AIMS: To explore the role of HTG in the pathogenesis of AP. METHODS: Thirty-six male SD rats were randomly assigned into normal control, AP, HTG, HTG-AP, low-dose fenofibrate and high-dose fenofibrate groups. Serum indices and cytokine levels in serum, and pathological changes in pancreatic tissues were observed. The expression levels of TLR4 and NF-κBp65 in pancreatic tissues were detected by immunohistochemistry and Western blot. RESULTS: In normal rats, HTG alone did not induce AP. However, after establishing the HTG-AP model with Poloxam 407 and L-arginine, serum-free fatty acid and TG levels were positively correlated with the levels of lipase, amylase, IL-1ß, IL-6, pancreatic inflammation scores, and the expressions of TLR4 and NF-κBp65 (all P < 0.001). Expressions of TLR4 and NF-κBp65 were significantly increased in the pancreatic tissues of HTG-AP rats. Fenofibrate effectively decreased TG levels in HTG-AP rats and reduced the expression of TLR4 and NF-κBp65 (all P < 0.001). CONCLUSIONS: HTG does not directly cause AP, but rather increases the susceptibility to AP or aggravates the inflammatory response. It is more like a sensitizer of inflammation rather than an activator.


Subject(s)
Hypertriglyceridemia , Pancreatitis , Rats, Sprague-Dawley , Toll-Like Receptor 4 , Triglycerides , Animals , Male , Pancreatitis/metabolism , Hypertriglyceridemia/complications , Triglycerides/blood , Triglycerides/metabolism , Toll-Like Receptor 4/metabolism , Rats , Pancreas/metabolism , Pancreas/pathology , Transcription Factor RelA/metabolism , Fenofibrate/pharmacology , Disease Models, Animal , Acute Disease , Arginine/blood , Hypolipidemic Agents/therapeutic use , Hypolipidemic Agents/pharmacology
10.
Plant Cell Rep ; 43(8): 195, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008098

ABSTRACT

KEY MESSAGE: ZmRLCK58, a negative growth regulator, reduces tolerance of maize seedlings to low Mg via enhancing H2O2 accumulation in the shoot. Magnesium (Mg) deficiency is one of critical limiting factors for crop production in widespread acidic soils worldwide. However, the molecular mechanism of crop response to Mg deficiency is still largely unclear. Here, we found higher concentrations of H2O2, soluble sugars, and starch (1.5-, 1.9-, and 1.4-fold, respectively) in the shoot of low-Mg-treated maize seedlings, compared with Mg sufficient plants under hydroponic culture. Consistent with over-accumulation of H2O2, transcriptome profiling revealed significant enrichment of 175 differentially expressed genes (DEGs) in "response to oxygen-containing compound" out of 641 DEGs in the shoot under low Mg. Among 175 DEGs, a down-regulated receptor-like cytoplasmic kinase ZmRLCK58 underwent a recent duplication event before Poaceae divergence and was highly expressed in the maize shoot. ZmRLCK58 overexpression enhanced H2O2 accumulation in shoots by 21.3% and 29.8% under control and low-Mg conditions, respectively, while reducing biomass accumulation compared with wild-type plants. Low Mg further led to 39.7% less starch accumulation in the ZmRLCK58 overexpression shoot and lower Mg utilization efficiency. Compared with wild-type plants, overall down-regulated expression of genes related to response to carbohydrate, photosynthesis, H2O2 metabolic, oxidation-reduction, and ROS metabolic processes in ZmRLCK58 overexpression lines preconditioned aforementioned physiological alterations. Together, ZmRLCK58, as a negative growth regulator, reduces tolerance of maize seedlings to low Mg via enhancing H2O2 accumulation.


Subject(s)
Gene Expression Regulation, Plant , Hydrogen Peroxide , Magnesium , Plant Proteins , Seedlings , Zea mays , Zea mays/genetics , Zea mays/metabolism , Zea mays/drug effects , Hydrogen Peroxide/metabolism , Seedlings/genetics , Seedlings/drug effects , Seedlings/metabolism , Gene Expression Regulation, Plant/drug effects , Magnesium/metabolism , Magnesium/pharmacology , Plant Proteins/metabolism , Plant Proteins/genetics , Starch/metabolism , Gene Expression Profiling , Plant Shoots/metabolism , Plant Shoots/genetics , Plant Shoots/drug effects , Plants, Genetically Modified
11.
Retina ; 44(7): 1209-1216, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38359396

ABSTRACT

PURPOSE: To explore the clinical value of ß-D-glucan (BDG) testing and metagenomic next-generation sequencing (mNGS) for detecting the pathogens of fungal endophthalmitis (FE). METHODS: This study included 32 cases (32 eyes) with FE and 20 cases (20 eyes) with intraocular inflammation caused by other etiologies. All patients underwent extraction of aqueous humor or vitreous fluid samples for BDG testing and mNGS. The diagnostic performance and total clinical concordance rate of BDG testing and mNGS for FE were evaluated and calculated based on the results of the clinical diagnosis. RESULTS: Among the clinically diagnosed FE, the positivity rates of BDG testing and mNGS (90.63%) were both significantly higher ( P < 0.001) than that of microbial cultures (53.13%). There was 100% consistency in pathogen identification using mNGS and culture identification for culture-positive cases. The area under the curve was 0.927 for BDG testing and 0.853 for mNGS. When the two tests were combined, sensitivity (93.75%), specificity (100.00%), and total clinical concordance rate (96.15%) were all improved, compared with the single tests. CONCLUSION: The positive rates of BDG test and mNGS were markedly higher than those of cultures in FE identification. The combination of these two tests showed improved performance when compared with individual tests.


Subject(s)
Aqueous Humor , Endophthalmitis , Eye Infections, Fungal , High-Throughput Nucleotide Sequencing , Metagenomics , Vitreous Body , beta-Glucans , Humans , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/microbiology , Endophthalmitis/diagnosis , Endophthalmitis/microbiology , Male , Middle Aged , Female , Aqueous Humor/microbiology , beta-Glucans/analysis , Vitreous Body/microbiology , Aged , Metagenomics/methods , Adult , Retrospective Studies , Fungi/isolation & purification , Fungi/genetics , DNA, Fungal/analysis , Proteoglycans , Aged, 80 and over
12.
Genomics ; 115(5): 110704, 2023 09.
Article in English | MEDLINE | ID: mdl-37678441

ABSTRACT

RNA N6-methyladenosine (m6A) modifications influence gastrointestinal stromal tumors (GISTs) development, but the detailed molecular mechanisms have not been fully studied. Here, microRNA-675 was found to be aberrantly elevated in cancerous tissues and cells of GISTs, compared to the corresponding normal counterparts, and GISTs patients with high-expressed microRNA-675 have worse outcomes. Additional experiments confirmed that silencing of microRNA-675 hindered cell division, mobility and tumorigenesis in vitro and in vivo, whereas triggered apoptotic cell death in GISTs cells. Furthermore, microRNA-675-ablation increased the expression levels of myosin phosphatase targeting protein 1 (MYPT1) to inactivate the tumor-initiating RhoA/NF2/YAP1 signal pathway, and downregulation of MYPT1 recovered the malignant phenotypes in microRNA-675-silenced GISTs cells. In addition, we evidenced that METTL3-mediated m6A modifications were essential for sustaining the stability of microRNA-675, and silencing of METTL3 restrained tumorigenesis of GISTs cells by regulating the microRNA-675/MYPT1 axis. To summarize, theMETTL3/m6A/microRNA-675/MYPT1 axis could be used as novel biomarkers for the diagnosis and treatment of GISTs.


Subject(s)
Gastrointestinal Stromal Tumors , MicroRNAs , Humans , Myosin-Light-Chain Phosphatase/genetics , Gastrointestinal Stromal Tumors/genetics , Methyltransferases/genetics , Carcinogenesis/genetics , MicroRNAs/genetics
13.
Ren Fail ; 46(2): 2368083, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38958248

ABSTRACT

OBJECTIVE: To identify the risk factors of refractory peritoneal dialysis related peritonitis (PDRP) and construct a nomogram to predict the occurrence of refractory PDRP. METHODS: Refractory peritonitis was defined as the peritonitis episode with persistently cloudy bags or persistent dialysis effluent leukocyte count >100 × 109/L after 5 days of appropriate antibiotic therapy. The study dataset was randomly divided into a 70% training set and a 30% validation set. Univariate logistic analysis, LASSO regression analysis, and random forest algorithms were utilized to identify the potential risk factors for refractory peritonitis. Independent risk factors identified using multivariate logistic analysis were used to construct a nomogram. The discriminative ability, calibrating ability, and clinical practicality of the nomogram were evaluated using the receiver operating characteristic curve, Hosmer-Lemeshow test, calibration curve, and decision curve analysis. RESULTS: A total of 294 peritonitis episodes in 178 patients treated with peritoneal dialysis (PD) were enrolled, of which 93 were refractory peritonitis. C-reactive protein, serum albumin, diabetes mellitus, PD duration, and type of causative organisms were independent risk factors for refractory peritonitis. The nomogram model exhibited excellent discrimination with an area under the curve (AUC) of 0.781 (95% CI: 0.716-0.847) in the training set and 0.741 (95% CI: 0.627-0.855) in the validation set. The Hosmer-Lemeshow test and calibration curve indicated satisfactory calibration ability of the predictive model. Decision curve analysis revealed that the nomogram model had good clinical utility in predicting refractory peritonitis. CONCLUSION: This nomogram can accurately predict refractory peritonitis in patients treated with PD.


Subject(s)
Nomograms , Peritoneal Dialysis , Peritonitis , Humans , Peritonitis/etiology , Peritonitis/diagnosis , Peritoneal Dialysis/adverse effects , Male , Female , Middle Aged , Risk Factors , Adult , Aged , ROC Curve , Retrospective Studies , Logistic Models , Anti-Bacterial Agents/therapeutic use , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/complications , C-Reactive Protein/analysis
14.
Molecules ; 29(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38611777

ABSTRACT

Iridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid components (catalpol (CAT), genipin (GE), geniposide (GEN), geniposidic acid (GPA), aucubin (AU), ajugol (AJU), rehmannioside C (RC), and rehmannioside D (RD)) based on corticosterone (CORT)-induced injury in PC12 cells. PC12 cells were randomly divided into a normal control group (NC), model group (M), positive drug group (FLX), and eight iridoid administration groups. Firstly, PC12 cells were induced with CORT to simulate neuronal injury. Then, the MTT method and flow cytometry were applied to evaluate the protective effects of eight iridoid components on PC12 cell damage. Thirdly, a cell metabolomics study based on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was performed to explore changes in relevant biomarkers and metabolic pathways following the intervention of administration. The MTT assay and flow cytometry analysis showed that the eight iridoid components can improve cell viability, inhibit cell apoptosis, reduce intracellular ROS levels, and elevate MMP levels. In the PCA score plots, the sample points of the treatment groups showed a trend towards approaching the NC group. Among them, AU, AJU, and RC had a weaker effect. There were 38 metabolites (19 metabolites each in positive and negative ion modes, respectively) identified as potential biomarkers during the experiment, among which 23 metabolites were common biomarkers of the eight iridoid groups. Pathway enrichment analysis revealed that the eight iridoid components regulated the metabolism mainly in relation to D-glutamine and D-glutamate metabolism, arginine biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism. In conclusion, the eight iridoid components could reverse an imbalanced metabolic state by regulating amino acid neurotransmitters, interfering with amino acid metabolism and energy metabolism, and harmonizing the level of oxidized substances to exhibit neuroprotective effects.


Subject(s)
Iridoid Glucosides , Iridoid Glycosides , Neuroprotective Agents , Pyrans , Animals , Rats , Neuroprotective Agents/pharmacology , Metabolomics , Iridoids/pharmacology , Amino Acids , Biomarkers
15.
Clin Immunol ; 250: 109295, 2023 05.
Article in English | MEDLINE | ID: mdl-36933629

ABSTRACT

Previous studies found cDC1s to be protective in early stage anti-GBM disease through Tregs, but pathogenic in late stage Adriamycin nephropathy through CD8+ T cells. Flt3 ligand is a growth factor essential for cDC1 development and Flt3 inhibitors are currently used for cancer treatment. We conducted this study to clarify the role and mechanisms of effects of cDC1s at different time points in anti-GBM disease. In addition, we aimed to utilize drug repurposing of Flt3 inhibitors to target cDC1s as a treatment of anti-GBM disease. We found that in human anti-GBM disease, the number of cDC1s increased significantly, proportionally more than cDC2s. The number of CD8+ T cells also increased significantly and their number correlated with cDC1 number. In XCR1-DTR mice, late (day 12-21) but not early (day 3-12) depletion of cDC1s attenuated kidney injury in mice with anti-GBM disease. cDC1s separated from kidneys of anti-GBM disease mice were found to have a pro-inflammatory phenotype (i.e. express high level of IL-6, IL-12 and IL-23) in late but not early stage. In the late depletion model, the number of CD8+ T cells was also reduced, but not Tregs. CD8+ T cells separated from kidneys of anti-GBM disease mice expressed high levels of cytotoxic molecules (granzyme B and perforin) and inflammatory cytokines (TNF-α and IFN-γ), and their expression reduced significantly after cDC1 depletion with diphtheria toxin. These findings were reproduced using a Flt3 inhibitor in wild type mice. Therefore, cDC1s are pathogenic in anti-GBM disease through activation of CD8+ T cells. Flt3 inhibition successfully attenuated kidney injury through depletion of cDC1s. Repurposing Flt3 inhibitors has potential as a novel therapeutic strategy for anti-GBM disease.


Subject(s)
Anti-Glomerular Basement Membrane Disease , CD8-Positive T-Lymphocytes , Drug Repositioning , fms-Like Tyrosine Kinase 3 , Animals , Humans , Mice , Anti-Glomerular Basement Membrane Disease/drug therapy , CD8-Positive T-Lymphocytes/metabolism , Dendritic Cells/metabolism , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , Kidney/metabolism , Signal Transduction
16.
Anal Chem ; 95(2): 1680-1685, 2023 Jan 17.
Article in English | MEDLINE | ID: mdl-36602469

ABSTRACT

Faraday rotation spectroscopy (FRS) exploits the magneto-optical effect to achieve highly selective and sensitive detection of paramagnetic molecules. Usually, a solenoid coil is used to provide a longitudinal magnetic field to produce the magneto-optical effect. However, such a method has the disadvantages of excessive power consumption and susceptibility to electromagnetic interference. In the present work, a novel FRS approach based on a combination of a neodymium iron boron permanent magnet ring array and a Herriott multipass absorption cell is proposed. A longitudinal magnetic field was generated by using 14 identical neodymium iron boron permanent magnet rings combined in a non-equidistant form according to their magnetic field's spatial distribution characteristics. The average magnetic field strength within a length of 380 mm was 346 gauss. A quantum cascade laser was used to target the optimum 441 ← 440 Q-branch nitrogen dioxide transition at 1613.25 cm-1 (6.2 µm) with an optical power of 40 mW. Coupling to a Herriott multipass absorption cell, a minimum detection limit of 0.4 ppb was achieved with an integration time of 70 s. The low-power FRS nitrogen dioxide sensor proposed in this work is expected to be developed into a robust field-deployable environment monitoring system.

17.
Opt Express ; 31(2): 3237-3248, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36785320

ABSTRACT

A novel CH4 sensor based on wavelength modulation spectroscopy with a multipass cell was developed for the soil respiration measurement of CH4. A home-made double-enhanced Herriot-type multipass cell with an effective absorption length of 73.926 m and a fiber-coupled distributed feedback diode laser emission at 1653.74 nm were used to design the sensor. The double enhancement of the effective optical pathlength of the multipass cell, absorption line locking, laser intensity normalization, and temperature control of the multipass cell were used to improve cell performance and achieve a minimum detection limit of 10 ppbv and a measurement precision of 6.4 ppbv. Finally, the potential of the developed CH4 sensor for ecological applications was verified by measuring the soil respiration of CH4 and monitoring of CH4 in the atmosphere over a long period.

18.
Inorg Chem ; 62(33): 13419-13427, 2023 Aug 21.
Article in English | MEDLINE | ID: mdl-37552876

ABSTRACT

The utilization of Cu-based catalysts in CO2 conversion into valuable chemicals is of significant interest due to their potential in mitigating greenhouse gas emissions. However, the controllable design of Cu-based catalysts and the regulation of their mechanism remain challenging. In this study, a series of efficient Cu/L catalysts were prepared for this process, and the intrinsic influencing factors on the reaction routes were systematically revealed. Various techniques revealed that Cu particles in L-supported catalysts exhibited higher dispersion and formed Cu-O(OH)-K interfacial sites. However, with increasing Cu loading, the dispersion of Cu particles and the percentage of Cu-O(OH)-K interfaces decreased. Kinetic investigations revealed that the adsorption configuration and electronic structure of Cu species codetermined the reaction pathways and resulting selectivity. Cu/L catalysts possessing Cu-O(OH)-K interfaces and small particles demonstrated the preferential formation of formate species, promoting methanol formation. However, larger Cu particles generated carboxylate intermediates, resulting in higher CO selectivity..

19.
Ren Fail ; 45(2): 2267127, 2023.
Article in English | MEDLINE | ID: mdl-37807904

ABSTRACT

OBJECTIVE: The serum triglyceride-glucose (TyG) index is a marker of inflammation. However, the relationship between TyG index and peritoneal dialysis-related peritonitis (PDRP) is unclear. This study aimed to investigate the potential relationship between the baseline TyG index and the initial episode of PDRP. METHODS: A total of 208 peritoneal dialysis (PD) patients were enrolled from January 1, 2012, to December 31, 2019 and followed up until December 31, 2022. They were divided into 2 groups according to the median TyG. The primary outcome was the occurrence of the initial episode of PDRP while on PD therapy. Kaplan-Meier curves and Cox regression analyses were used to examine the association between them. RESULTS: Eighty-five initial episodes of PDRP were identified. The risk of PDRP was higher in the high-TyG index group (p = 0.030). Multivariate Cox regression analysis showed a higher risk of PDRP in patients with a high TyG index (HR = 1.800, 95% CI 1.511-2.815, p = 0.010). CONCLUSION: The baseline serum TyG index was an independent risk factor for the initial episode of PDRP in chronic PD patients.


Subject(s)
Kidney Failure, Chronic , Peritoneal Dialysis , Peritonitis , Humans , Glucose , Triglycerides , Retrospective Studies , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/epidemiology , Peritoneal Dialysis/adverse effects , Peritonitis/epidemiology , Peritonitis/etiology , Risk Factors , Blood Glucose , Biomarkers
20.
Entropy (Basel) ; 25(2)2023 Jan 31.
Article in English | MEDLINE | ID: mdl-36832635

ABSTRACT

Poor chip solder joints can severely affect the quality of the finished printed circuit boards (PCBs). Due to the diversity of solder joint defects and the scarcity of anomaly data, it is a challenging task to automatically and accurately detect all types of solder joint defects in the production process in real time. To address this issue, we propose a flexible framework based on contrastive self-supervised learning (CSSL). In this framework, we first design several special data augmentation approaches to generate abundant synthetic, not good (sNG) data from the normal solder joint data. Then, we develop a data filter network to distill the highest quality data from sNG data. Based on the proposed CSSL framework, a high-accuracy classifier can be obtained even when the available training data are very limited. Ablation experiments verify that the proposed method can effectively improve the ability of the classifier to learn normal solder joint (OK) features. Through comparative experiments, the classifier trained with the help of the proposed method can achieve an accuracy of 99.14% on the test set, which is better than other competitive methods. In addition, its reasoning time is less than 6 ms per chip image, which is in favor of the real-time defect detection of chip solder joints.

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