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1.
PLoS One ; 19(6): e0303582, 2024.
Article in English | MEDLINE | ID: mdl-38917067

ABSTRACT

China is transitioning into the digital economy era. The advancement of the digital economy could offer a fresh mechanism to attain carbon peak and carbon neutrality objectives. Applications of the digital economy, such as smart energy management, intelligent transport systems, and digital agricultural technologies, have significantly reduced carbon emissions by optimizing resource use, reducing energy waste, and improving production efficiency. This research does so by devising a theoretical model that looks into the multi-faceted power of the digital economy under a two-sector paradigm. Utilising a panel model, a mediation effect model and a spatial Durbin model to assess the digital economy's power on carbon emissions. This research has determined that the digital economy can significantly diminish carbon emissions, with green tech innovations and industrial transformation being key contributors. The spatial spillover effect was used for the digital economy to aid in lowering carbon emissions in adjacent districts and upgrading better environmental stewardship. The influence of the digital economy has better performance in lowering carbon emissions in mid-western China than in the eastern area. This paper deepens understanding of the drivers of low-carbon growth and the significance, mechanism and regional disparities of the digital economy's effect on reducing carbon emissions. It offers valuable policy insights and guidance for globally achieving digital economy growth, reducing carbon emissions and reaching carbon peak and neutrality goals.


Subject(s)
Carbon , China , Carbon/metabolism , Carbon Dioxide/analysis , Models, Theoretical , Agriculture/methods , Agriculture/economics , Economic Development , Air Pollution/prevention & control , Air Pollution/analysis , Humans
2.
Oncol Lett ; 28(2): 348, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38872856

ABSTRACT

Skin metastasis from ovarian cancer is rare, and its prognosis is poor. Effective therapeutic strategies are currently lacking, but the combination of various treatment methods shrink the tumor and relieve symptoms. The present study reports a rare case of advanced ovarian cancer with skin metastases and intestinal wall thickening, along with a BRCA1 DNA repair associated (BRCA1) mutation. After standard first-line treatment and non-standard second-line treatment, the patient developed skin metastases. The patient's skin itching, pain and lesions were completely relieved after administering bevacizumab in combination with paclitaxel and carboplatin. After 4 months, skin metastases recurred along with anal distension during maintenance treatment with oral poly(ADP ribose) polymerase (PARP) inhibitors. The patient was treated again with bevacizumab combined with docetaxel, and the anal distension was significantly relieved. Angiogenesis therapy combined with chemotherapy is effective, but that the disease-free survival time is short, and PARP inhibitor maintenance effect is limited even in cases with a BRCA1 gene mutation.

3.
Cancer Gene Ther ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877164

ABSTRACT

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

4.
Clin Transl Med ; 14(6): e1734, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38888967

ABSTRACT

BACKGROUND: Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. METHODS: Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. RESULTS: There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. CONCLUSIONS: We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. HIGHLIGHTS: Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.


Subject(s)
Adenoma , Histone-Lysine N-Methyltransferase , Inflammation , Parathyroid Neoplasms , Humans , Parathyroid Neoplasms/genetics , Parathyroid Neoplasms/metabolism , Parathyroid Neoplasms/pathology , Adenoma/genetics , Adenoma/metabolism , Adenoma/pathology , Inflammation/genetics , Inflammation/metabolism , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Myeloid-Lymphoid Leukemia Protein/genetics , Myeloid-Lymphoid Leukemia Protein/metabolism , Proto-Oncogene Mas , Cell Proliferation/genetics
5.
J Environ Manage ; 364: 121379, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38870787

ABSTRACT

Chemical nutrient amendment by human activities can lead to environmental impacts contributing to global biodiversity loss. However, the comprehensive understanding of how below- and above-ground biodiversity shifts under fertilization regimes in natural ecosystems remains elusive. Here, we conducted a seven-year field experiment (2011-2017) and examined the effects of different fertilization on plant biodiversity and soil belowground (prokaryotic and eukaryotic) communities in the alpine meadow of the Tibetan Plateau, based on data collected in 2017. Our results indicate that nitrogen addition promoted total plant biomass but reduced the plant species richness. Conversely, phosphorus enrichment did not promote plant biomass and exhibited an unimodal pattern with plant richness. In the belowground realm, distinct responses of soil prokaryotic and eukaryotic communities were observed under fertilizer application. Specifically, soil prokaryotic diversity decreased with nitrogen enrichment, correlating with shifts in soil pH. Similarly, soil eukaryotic diversity decreased with increased phosphorous inputs, aligning with the equilibrium between soil available and total phosphorus. We also established connections between these soil organism communities with above-ground plant richness and biomass. Overall, our study contributes to a better understanding of the sustainable impacts of human-induced nutrient enrichment on the natural environment. Future research should delve deeper into the long-term effects of fertilization on soil health and ecosystem functioning, aiming to achieve a balance between agricultural productivity and environmental conservation.


Subject(s)
Biodiversity , Fertilizers , Soil , Tibet , Soil/chemistry , Ecosystem , Phosphorus/analysis , Soil Microbiology , Biomass , Nitrogen , Agriculture
6.
Hepatol Int ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913149

ABSTRACT

BACKGROUND AND AIMS: The efficacy of achieving HBsAg clearance through pegylated interferon (PEG-IFNα) therapy in patients with chronic hepatitis B (CHB) remains uncertain, especially regarding the probability of achieving functional cure among patients with varying baseline HBsAg levels. We aimed to investigate the predictive value of HBsAg quantification for HBsAg seroclearance in CHB patients undergoing PEG-IFNα treatment. METHODS: A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to January 11, 2022. Subgroup analyses were performed for HBeAg-positive and HBeAg-negative patients, PEG-IFNα monotherapy and PEG-IFNα combination therapy, treatment-naive and treatment-experienced patients, and patients with or without liver cirrhosis. RESULTS: This predictive model incorporated 102 studies. The overall HBsAg clearance rates at the end of treatment (EOT) and the end of follow-up (EOF) were 10.6% (95% CI 7.8-13.7%) and 11.1% (95% CI 8.4-14.1%), respectively. Baseline HBsAg quantification was the most significant factor. According to the model, it is projected that when baseline HBsAg levels are 100, 500, 1500, and 10,000 IU/ml, the HBsAg clearance rates at EOF could reach 53.9% (95% CI 40.4-66.8%), 32.1% (95% CI 24.8-38.7%), 14.2% (95% CI 9.8-18.8%), and 7.9% (95% CI 4.2-11.8%), respectively. Additionally, treatment-experienced patients with HBeAg-negative status, and without liver cirrhosis exhibited higher HBsAg clearance rates after PEG-IFNα treatment. CONCLUSION: A successful predictive model has been established to predict the achievement of functional cure in CHB patients receiving PEG-IFNα therapy.

7.
Phytomedicine ; 130: 155687, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38759312

ABSTRACT

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a debilitating interstitial lung disorder characterized by its limited therapeutic interventions. Macrophages, particularly the alternatively activated macrophages (M2 subtype), have been acknowledged for their substantial involvement in the development of pulmonary fibrosis. Hence, targeting macrophages emerges as a plausible therapeutic avenue for IPF. Icariside II (ISE II) is a natural flavonoid glycoside molecule known for its excellent anti-tumor and anti-fibrotic activities. Nevertheless, the impact of ISE II on pulmonary fibrosis and the intricate mechanisms through which it operates have yet to be elucidated. OBJECTIVE: To scrutinize the impact of ISE II on the regulation of M2 macrophage polarization and its inhibitory effect on pulmonary fibrosis, as well as to delve deeper into the underlying mechanisms of its actions. METHODS: The effect of ISE II on proliferation and apoptosis in RAW264.7 cells was assessed through the use of EdU-488 labeling and the Annexin V/PI assay. Flow cytometry, western blot, and qPCR were employed to detect markers associated with the M2 polarization phenotype. The anti-fibrotic effects of ISE II in NIH-3T3 cells were investigated in a co-culture with M2 macrophages. Si-Ctnnb1 and pcDNA3.1(+)-Ctnnb1 plasmid were used to investigate the mechanism of targeted intervention. The murine model of pulmonary fibrosis was induced by intratracheal administration of bleomycin (BLM). Pulmonary function, histopathological manifestations, lung M2 macrophage infiltration, and markers associated with pulmonary fibrosis were evaluated. Furthermore, in vivo transcriptomics analysis was employed to elucidate differentially regulated genes in lung tissues. Immunofluorescence, western blot, and immunohistochemistry were conducted for corresponding validation. RESULTS: Our investigation demonstrated that ISE II effectively inhibited the proliferation of RAW264.7 cells and mitigated the pro-fibrotic characteristics of M2 macrophages, exemplified by the downregulation of CD206, Arg-1, and YM-1, Fizz1, through the inhibition of the PI3K/Akt/ß-catenin signaling pathway. This impact led to the amelioration of myofibroblast activation and the suppression of nuclear translocation of ß-catenin of NIH-3T3 cells in a co-culture. Consequently, it resulted in decreased collagen deposition, reduced infiltration of profibrotic macrophages, and a concurrent restoration of pulmonary function in mice IPF models. Furthermore, our RNA sequencing results showed that ISE II could suppress the expression of genes related to M2 polarization, primarily by inhibiting the PI3K/Akt and ß-catenin signaling pathway. In essence, our findings suggest that ISE II holds potential as an anti-fibrotic agent by orchestrating macrophage polarization. This may have significant implications in clinical practice. CONCLUSION: This study has provided evidence that ISE II exerts a significant anti-fibrotic effect by inhibiting macrophage M2 polarization through the suppression of the PI3K/Akt/ß-catenin signaling pathway. These findings underscore the potential of ISE II as a promising candidate for the development of anti-fibrotic pharmaceuticals in the future.


Subject(s)
Flavonoids , Macrophages , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , beta Catenin , Animals , Mice , Proto-Oncogene Proteins c-akt/metabolism , Flavonoids/pharmacology , RAW 264.7 Cells , Macrophages/drug effects , Macrophages/metabolism , beta Catenin/metabolism , Phosphatidylinositol 3-Kinases/metabolism , NIH 3T3 Cells , Cell Proliferation/drug effects , Signal Transduction/drug effects , Bleomycin , Mice, Inbred C57BL , Apoptosis/drug effects , Male , Idiopathic Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/drug therapy
8.
Cell Rep Med ; 5(5): 101519, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38692271

ABSTRACT

Osteosarcoma (OS) is the most common malignant bone tumor with a poor prognosis. Here, we show that the nuclear receptor RORγ may serve as a potential therapeutic target in OS. OS exhibits a hyperactivated oxidative phosphorylation (OXPHOS) program, which fuels the carbon source to promote tumor progression. We found that RORγ is overexpressed in OS tumors and is linked to hyperactivated OXPHOS. RORγ induces the expression of PGC-1ß and physically interacts with it to activate the OXPHOS program by upregulating the expression of respiratory chain component genes. Inhibition of RORγ strongly inhibits OXPHOS activation, downregulates mitochondrial functions, and increases ROS production, which results in OS cell apoptosis and ferroptosis. RORγ inverse agonists strongly suppressed OS tumor growth and progression and sensitized OS tumors to chemotherapy. Taken together, our results indicate that RORγ is a critical regulator of the OXPHOS program in OS and provides an effective therapeutic strategy for this deadly disease.


Subject(s)
Bone Neoplasms , Mitochondria , Nuclear Receptor Subfamily 1, Group F, Member 3 , Osteosarcoma , Oxidative Phosphorylation , Osteosarcoma/metabolism , Osteosarcoma/pathology , Osteosarcoma/genetics , Humans , Oxidative Phosphorylation/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Cell Line, Tumor , Animals , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/genetics , Bone Neoplasms/drug therapy , Mice , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Gene Expression Regulation, Neoplastic , Ferroptosis/genetics , Ferroptosis/drug effects , Mice, Nude , Male , Cell Proliferation , RNA-Binding Proteins
9.
J Agric Food Chem ; 72(23): 12915-12924, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38807027

ABSTRACT

Plant pathogenic fungi pose a significant threat to agricultural production, necessitating the development of new and more effective fungicides. The ring replacement strategy has emerged as a highly successful approach in molecular design. In this study, we employed the ring replacement strategy to successfully design and synthesize 32 novel hydrazide derivatives containing diverse heterocycles, such as thiazole, isoxazole, pyrazole, thiadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, thiophene, pyridine, and pyrazine. Their antifungal activities were evaluated in vitro and in vivo. Bioassay results revealed that most of the title compounds displayed remarkable antifungal activities in vitro against four tested phytopathogenic fungi, including Fusarium graminearum, Botrytis cinerea, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound 5aa displayed a broad spectrum of antifungal activity against F. graminearum, B. cinerea, S. sclerotiorum, and R. solani, with the corresponding EC50 values of 0.12, 4.48, 0.33, and 0.15 µg/mL, respectively. In the antifungal growth assay, compound 5aa displayed a protection efficacy of 75.5% against Fusarium head blight (FHB) at a concentration of 200 µg/mL. In another in vivo antifungal activity evaluation, compound 5aa exhibited a noteworthy protective efficacy of 92.0% against rape Sclerotinia rot (RSR) at a concentration of 100 µg/mL, which was comparable to the positive control tebuconazole (97.5%). The existing results suggest that compound 5aa has a broad-spectrum antifungal activity. Electron microscopy observations showed that compound 5aa might cause mycelial abnormalities and organelle damage in F. graminearum. Moreover, in the in vitro enzyme assay, we found that the target compounds 5aa, 5ab, and 5ca displayed significant inhibitory effects toward succinate dehydrogenase, with the corresponding IC50 values of 1.62, 1.74, and 1.96 µM, respectively, which were superior to that of boscalid (IC50 = 2.38 µM). Additionally, molecular docking and molecular dynamics simulation results revealed that compounds 5aa, 5ab, and 5ca have the capacity to bind in the active pocket of succinate dehydrogenase (SDH), establishing hydrogen-bonding interactions with neighboring amino acid residues.


Subject(s)
Ascomycota , Botrytis , Drug Design , Fungicides, Industrial , Fusarium , Plant Diseases , Rhizoctonia , Succinate Dehydrogenase , Succinate Dehydrogenase/antagonists & inhibitors , Fusarium/drug effects , Fusarium/growth & development , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Structure-Activity Relationship , Ascomycota/drug effects , Botrytis/drug effects , Botrytis/growth & development , Rhizoctonia/drug effects , Plant Diseases/microbiology , Molecular Docking Simulation , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Fungal Proteins/antagonists & inhibitors , Fungal Proteins/chemistry , Fungal Proteins/metabolism , Microbial Sensitivity Tests , Hydrazines/pharmacology , Hydrazines/chemistry , Hydrazines/chemical synthesis , Molecular Structure , Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/chemical synthesis
11.
Sci Rep ; 14(1): 10451, 2024 05 07.
Article in English | MEDLINE | ID: mdl-38714716

ABSTRACT

This study aimed to retrospectively analyze the perioperative and postoperative follow-up data of patients with super obesity who had undergone RYGB, SG, BPD/DS, and SADI-S. A retrospective observational study was conducted to analyze the perioperative and postoperative follow-up data of 60 patients with super obesity who had undergone bariatric surgery. A total of 34 men and 26 women were included in this study. The participants had an average preoperative BMI of 53.81 ± 3.25 kg/m2. The body weight and BMI of all four patient groups decreased significantly at 3, 6, and 12 months postoperatively compared with the preoperative values. Additionally, the TWL (%) and EWL (%) of all four groups increased gradually over the same period. Compared with the preoperative values, the systolic and diastolic blood pressure, glycosylated hemoglobin, uric acid, triglycerides, and total cholesterol decreased to varying degrees in the four groups 1 year postoperatively. RYGB, SG, BPD/DS, and SADI-S are all safe and effective in treating super obese patients and improving their metabolic diseases to a certain extent.


Subject(s)
Bariatric Surgery , Body Mass Index , Obesity, Morbid , Humans , Male , Female , Adult , Obesity, Morbid/surgery , Obesity, Morbid/complications , Retrospective Studies , Middle Aged , Bariatric Surgery/methods , Treatment Outcome , China , Weight Loss , Follow-Up Studies , East Asian People
13.
Nat Commun ; 15(1): 4489, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802385

ABSTRACT

The sensitivity of soil organic carbon (SOC) decomposition in seasonally frozen soils, such as alpine ecosystems, to climate warming is a major uncertainty in global carbon cycling. Here we measure soil CO2 emission during four years (2018-2021) from the whole-soil warming experiment (4 °C for the top 1 m) in an alpine grassland ecosystem. We find that whole-soil warming stimulates total and SOC-derived CO2 efflux by 26% and 37%, respectively, but has a minor effect on root-derived CO2 efflux. Moreover, experimental warming only promotes total soil CO2 efflux by 7-8% on average in the meta-analysis across all grasslands or alpine grasslands globally (none of these experiments were whole-soil warming). We show that whole-soil warming has a much stronger effect on soil carbon emission in the alpine grassland ecosystem than what was reported in previous warming experiments, most of which only heat surface soils.

15.
J Environ Manage ; 358: 120922, 2024 May.
Article in English | MEDLINE | ID: mdl-38657413

ABSTRACT

In order to deal with the environmental problems such as pollution emissions and climate change, sustainable development in the field of transportation has gradually become a hot topic to all sectors of society. In addition, promoting the green and low-carbon transformation of China's transportation is also an important issue in the new era. Thus, it is particularly important to correctly identify the green effect of high-speed rail. However, the traditional causal reasoning model faces several challenges such as 'dimensional curse' and multicollinearity. Based on the panel data of 283 prefecture-level cities in China from 2003 to 2019, this study uses the double machine learning model to explore the impact of transportation infrastructure upgrading on the efficiency of urban green development in China. The research shows that the upgrading of transportation infrastructure can effectively improve the efficiency of urban green development by 4%. Service industry agglomeration and green innovation are verified as two mediating channels. Moreover, the synthetic difference in difference model is employed to evaluate the regional impact of high-speed rail, and finds that the regional impact of transportation policies often exceeds the impact of individual cities. We further apply the conclusions of this paper to the research at the micro enterprise level. Goodman-Bacon decomposition and a variety of robustness tests confirm the validity of our conclusions. The study's comprehensive empirical analysis not only validates the positive effects of transportation upgrades on green development, but also offers novel insights into the underlying mechanisms and policy implications of transportation upgrading.


Subject(s)
Cities , Machine Learning , Sustainable Development , Transportation , China , Models, Theoretical , Climate Change
16.
Sensors (Basel) ; 24(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38676010

ABSTRACT

Aiming at the problems of target detection models in traffic scenarios including a large number of parameters, heavy computational burden, and high application cost, this paper introduces an enhanced lightweight real-time detection algorithm, which exhibits higher detection speed and accuracy for vehicle detection. This paper considers the YOLOv7 algorithm as the benchmark model, designs a lightweight backbone network, and uses the MobileNetV3 lightweight network to extract target features. Inspired by the structure of SPPF, the spatial pyramid pooling module is reconfigured by incorporating GSConv, and a lightweight SPPFCSPC-GS module is designed, aiming to minimize the quantity of model parameters and enhance the training speed even further. Furthermore, the CA mechanism is integrated to enhance the feature extraction capability of the model. Finally, the MPDIoU loss function is utilized to optimize the model's training process. Experiments showcase that the refined YOLOv7 algorithm can achieve 98.2% mAP on the BIT-Vehicle dataset with 52.8% fewer model parameters than the original model and a 35.2% improvement in FPS. The enhanced model adeptly strikes a finer equilibrium between velocity and precision, providing favorable conditions for embedding the model into mobile devices.

17.
Platelets ; 35(1): 2337255, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38630028

ABSTRACT

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.


What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.


Subject(s)
Exosomes , Humans , Sodium Citrate , Temperature , Anticoagulants/pharmacology , Anticoagulants/therapeutic use , Heparin , Membrane Proteins , Biomarkers
18.
World J Hepatol ; 16(3): 405-417, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38577530

ABSTRACT

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

19.
Mol Neurobiol ; 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38573415

ABSTRACT

This study investigates the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a nonpharmacological approach to treating neuropathic pain (NP), a major challenge in clinical research. Conducted on male Sprague-Dawley rats with NP induced through chronic constriction injury of the sciatic nerve, the research assessed pain behaviors and the impact of rTMS on molecular interactions within the amygdala. Through a comprehensive analysis involving Mechanical Withdrawal Threshold (MWT), Thermal Withdrawal Latency (TWL), RNA transcriptome sequencing, RT-qPCR, Western blotting, immunofluorescence staining, and Co-Immunoprecipitation (Co-IP), the study focused on the expression and interaction of integrin αvß3 and its receptor P2X7R. Findings reveal that rTMS significantly influences the expression of integrin αvß3 in NP models, suggesting an inhibition of the NP-associated NLRP3 inflammatory pathway through the disruption of integrin αvß3-P2X7R interactions. These outcomes highlight the potential of rTMS in alleviating NP by targeting molecular interactions within the amygdala, offering a promising therapeutic avenue for managing NP.

20.
World J Hepatol ; 16(2): 146-151, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38495283

ABSTRACT

We read with interest the article by Xing Wang, which was published in the recent issue of the World Journal of Hepatology 2023; 15: 1294-1306. This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis (LC), prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma (HCC), and management strategies. The etiology of cirrhosis varies according to geographical, economic, and population factors. Viral hepatitis is the dominant cause in China. Vaccination and effective treatment have reduced the number of people with viral hepatitis, but the overall number is still large. Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage. The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease (MASLD)-associated LC and alcoholic liver disease in the future. Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development. These changing trends indicate a need for greater emphasis on tackling obesity and diabetes, and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD. In an effort to help cope with these changing trends, the authors further proposed countermeasures for healthcare authorities doctors, and patients.

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