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1.
Article in English | MEDLINE | ID: mdl-38832458

ABSTRACT

Emissions from road traffic and residential heating contribute to urban air pollution. Advances in emission reduction technologies may alter the composition of emissions and affect their fate during atmospheric processing. Here, emissions of a gasoline car and a wood stove, both equipped with modern emission mitigation technology, were photochemically aged in an oxidation flow reactor to the equivalent of one to five days of photochemical aging. Fresh and aged exhausts were analyzed by ultrahigh resolution mass spectrometry. The gasoline car equipped with a three-way catalyst and a gasoline particle filter emitted minor primary fine particulate matter (PM2.5), but aging led to formation of particulate low-volatile, oxygenated and highly nitrogen-containing compounds, formed from volatile organic compounds (VOCs) and gases incl. NOx, SO2, and NH3. Reduction of the particle concentration was also observed for the application of an electrostatic precipitator with residential wood combustion but with no significant effect on the chemical composition of PM2.5. Comparing the effect of short and medium photochemical exposures on PM2.5 of both emission sources indicates a similar trend for formation of new organic compounds with increased carbon oxidation state and nitrogen content. The overall bulk compositions of the studied emission exhausts became more similar by aging, with many newly formed elemental compositions being shared. However, the presence of particulate matter in wood combustion results in differences in the molecular properties of secondary particles, as some compounds were preserved during aging.

2.
Sci Rep ; 14(1): 14149, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898041

ABSTRACT

Using the principles of density functional theory (DFT) and nonequilibrium Green's function (NEGF), We thoroughly researched carbon-doped zigzag boron nitride nanoribbons (ZBNNRs) to understand their electronic behavior and transport properties. Intriguingly, we discovered that careful doping can transform carbon-doped ZBNNRs into a spintronic nanodevice with distinct transport features. Our model showed a giant magnetoresistance (GMR) up to a whopping 10 5 under mild bias conditions. Plus, we spotted a spin rectifier having a significant rectification ratio (RR) of 10 4 . Our calculated transmission spectra have nicely explained why there's a GMR up to 10 5 for spin-up current at biases of - 1.2 V, - 1.1 V, and - 1.0 V, and also accounted for a GMR up to 10 3 -10 5 for spin-down current at biases of 1.0 V, 1.1 V, and 1.2 V. Similarly, the transmission spectra elucidate that at biases of 1.0 V, 1.1 V, and 1.2 V for spin-up, and at biases of 1.1 V and 1.2 V for spin-down in APMO, the RRs reach 10 4 . Our research shines a light on a promising route to push forward the high-performance spintronics technology of ZBNNRs using carbon atom doping. These insights hint that our models could be game-changers in the sphere of nanoscale spintronic devices.

3.
Blood Adv ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861356

ABSTRACT

ß-thalassemia is a condition characterized by reduced or absent synthesis of ß-globin resulting from genetic mutations, leading to expanded and ineffective erythropoiesis. Mitoxantrone has been widely used clinically as an antitumor agent in light of its ability to inhibit cell proliferation. However, its therapeutic effect on expanded and ineffective erythropoiesis in ß-thalassemia is untested. We found that mitoxantrone decreased α-globin precipitates and ameliorated anemia, splenomegaly and ineffective erythropoiesis in the HbbTh3/+ mouse model of ß-thalassemia intermedia. The partially reversed ineffective erythropoiesis is a consequence of effects on autophagy as mitochondrial retention and protein levels of mTOR, P62 and LC3 in reticulocytes decreased in mitoxantrone-treated HbbTh3/+ mice. These data provide significant pre-clinical evidence for targeting autophagy as a novel therapeutic approach for ß-thalassemia.

4.
BMC Cancer ; 24(1): 727, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877445

ABSTRACT

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hepatectomy , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Male , Female , Middle Aged , Prognosis , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Aged , ROC Curve , Retrospective Studies , Kaplan-Meier Estimate , Adult , Risk Factors
5.
Environ Sci Technol ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38885439

ABSTRACT

Understanding of nitrous acid (HONO) production is crucial to photochemical studies, especially in polluted environments like eastern China. In-situ measurements of gaseous and particulate compositions were conducted at a rural coastal site during the 2018 spring Ozone Photochemistry and Export from China Experiment (OPECE). This data set was applied to investigate the recycling of reactive nitrogen through daytime heterogeneous HONO production. Although HONO levels increase during agricultural burning, analysis of the observation data does not indicate more efficient HONO production by agricultural burning aerosols than other anthropogenic aerosols. Box and 1-D modeling analyses reveal the intrinsic relationships between nitrogen dioxide (NO2), particulate nitrate (pNO3), and nitric acid (HNO3), resulting in comparable agreement between observed and simulated HONO concentrations with any one of the three heterogeneous HONO production mechanisms, photosensitized NO2 conversion on aerosols, photolysis of pNO3, and conversion from HNO3. This finding underscores the uncertainties in the mechanistic understanding and quantitative parametrizations of daytime heterogeneous HONO production pathways. Furthermore, the implications for reactive nitrogen recycling, ozone (O3) production, and O3 control strategies vary greatly depending on the HONO production mechanism. On a regional scale, the conversion of HONO from pNO3 can drastically enhance O3 production, while the conversion from NO2 can reduce O3 sensitivity to NOx changes in polluted eastern China.

6.
Anal Chem ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874382

ABSTRACT

Dysregulation of protein core-fucosylation plays a pivotal role in the onset, progression, and immunosuppression of cancer. However, analyzing core-fucosylation, especially the accurate determination of the core-fucosylation (CF) site occupancy ratio, remains challenging. To address these problems, we developed a truncation strategy that efficiently converts intact glycopeptides with hundreds of different glycans into two truncated forms, i.e., a monosaccharide HexNAc and a disaccharide HexNAc+core-fucose. Further combination with data-independent analysis to form an integrated platform allowed the measurement of site-specific core-fucosylation abundances and the determination of the CF occupancy ratio with high reproducibility. Notably, three times CF sites were identified using this strategy compared to conventional methods based on intact glycopeptides. Application of this platform to characterize protein core-fucosylation in two breast cancer cell lines, i.e., MDA-MB-231 and MCF7, yields a total of 1615 unique glycosites and about 900 CF sites from one single LC-MS/MS analysis. Differential analysis unraveled the distinct glycosylation pattern for over 201 cell surface drug targets between breast cancer subtypes and provides insights into developing new therapeutic strategies to aid precision medicine. Given the robust performance of this platform, it would have broad application in discovering novel biomarkers based on the CF glycosylation pattern, investigating cancer mechanisms, as well as detecting new intervention targets.

7.
Int J Surg ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913440

ABSTRACT

BACKGROUND: Visceral pain occurs commonly following thoracic surgery, but an effective method to relieve visceral pain in thoracic surgery remains controversial. We test the effect of stellate ganglion blocks (SGB) on perioperative visceral pain following video-assisted thoracoscopic surgery (VATS). METHODS: A prospective, randomized, controlled trial enrolled 77 elderly patients undergoing VATS. Patients were randomized to SGB followed by modified intercostal nerve block (Group S, n=37); or modified intercostal nerve block only (Group C, n=40). Remifentanil 0.02-0.2 µg·kg-1·min-1 was titrated to keep pain threshold index values between 40-65 and maintain mean arterial pressure or heart rate values around 20% of baseline values. Patient-controlled intravenous analgesia with sufentanil was used in the postoperative period. The co-primary outcomes were the perioperative cumulative opioid consumption and pain scores on movement at 24 h after surgery. RESULTS: Compared with control group, SGB greatly reduced the intraoperative remifentanil consumption[300.00(235.00-450.00)µg versus 710.00(500.00-915.00)µg; P<0.01], with no difference in cumulative sufentanil consumption to 48h post-surgery. There was a statistically significant difference in pain scores on movement at 24h between groups [4.00(3.00-4.00) versus 4.00(3.25-5.00); P=0.01]. Further exploratory analyses showed significant difference for intra-chest pain on movement at 24h [3.00(2.00-3.00) versus 3.00(2.25-4.00); P=0.01]. No significant difference was observed in nausea/vomiting, time to pass flatus and postoperative length of stay. CONCLUSION: Preoperative stellate ganglion blocks for elderly patients could effectively blunt intraoperative visceral stress and reduce postoperative visceral pain extending 24 h after VATS. This initial finding deserve further investigation.

8.
PLoS One ; 19(6): e0303478, 2024.
Article in English | MEDLINE | ID: mdl-38837996

ABSTRACT

Our study explores whether lifelong learning is associated with the subjective wellbeing among the elderly in Singapore. Through a primary survey of 300 individuals aged 65 and above, we develop a novel index to capture three different aspects of subjective wellbeing, which we term "Quality of Life", "Satisfaction with Life" and "Psychological Wellbeing". Utilizing both supervised and unsupervised machine learning techniques, our findings reveal that attitudes towards lifelong learning are positively associated with quality of life, while participation in class activities is positively associated with all three measures of wellbeing. Although the study does not establish causality, it highlights a connection between lifelong learning and the perceived wellbeing of the elderly, offering support for policies that encourage lifelong learning among this population.


Subject(s)
Machine Learning , Personal Satisfaction , Quality of Life , Humans , Singapore , Aged , Female , Male , Aged, 80 and over , Learning , Surveys and Questionnaires
9.
PLoS One ; 19(5): e0302992, 2024.
Article in English | MEDLINE | ID: mdl-38713664

ABSTRACT

Bean beetle (Callosobruchus maculatus) exhibits clear phenotypic plasticity depending on population density; However, the underlying molecular mechanism remains unknown. Compared to low-density individuals, high-density individuals showed a faster terminal oocyte maturity rate. Four insulin-like peptide (ILP) genes were identified in the bean beetle, which had higher expression levels in the head than in the thorax and abdomen. The population density could regulate the expression levels of CmILP1-3, CmILP2-3, and CmILP1 as well as CmILP3 in the head, thorax, and abdomen, respectively. RNA interference results showed that each CmILP could regulate terminal oocyte maturity rate, indicating that there was functional redundancy among CmILPs. Silencing each CmILP could lead to down-regulation of some other CmILPs, however, CmILP3 was up-regulated in the abdomen after silencing CmILP1 or CmILP2. Compared to single gene silencing, silencing CmILP3 with CmILP1 or CmILP2 at the same time led to more serious retardation in oocyte development, suggesting CmILP3 could be up-regulated to functionally compensate for the down-regulation of CmILP1 and CmILP2. In conclusion, population density-dependent plasticity in terminal oocyte maturity rate of bean beetle was regulated by CmILPs, which exhibited gene redundancy and gene compensation.


Subject(s)
Coleoptera , Oocytes , Animals , Coleoptera/genetics , Coleoptera/metabolism , Oocytes/metabolism , Oocytes/growth & development , Female , RNA Interference , Insect Proteins/genetics , Insect Proteins/metabolism , Insulin/metabolism , Insulin/genetics , Population Density , Insulin-Like Peptides
10.
Viruses ; 16(5)2024 05 06.
Article in English | MEDLINE | ID: mdl-38793618

ABSTRACT

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain a latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV)-latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells and SeMNPV or Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells, and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in the G2/M phase or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that, compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, budded virus (BV) production and occlusion body (OB)-containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post-infection (p < 0.05). Finally, the arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB-containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression and regulation.


Subject(s)
G2 Phase Cell Cycle Checkpoints , Nucleopolyhedroviruses , Spodoptera , Superinfection , Virus Replication , Animals , Nucleopolyhedroviruses/physiology , Cell Line , Spodoptera/virology , Superinfection/virology , G1 Phase
11.
PLoS One ; 19(5): e0303506, 2024.
Article in English | MEDLINE | ID: mdl-38771826

ABSTRACT

OBJECTIVE: To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially expressed genes (DEGs) in patient synovial cells, aiming to provide new insights for clinical treatment strategies. MATERIALS AND METHODS: Gene expression datasets GSE1919, GSE82107, and GSE77298 were downloaded from the Gene Expression Omnibus (GEO) database to serve as the training groups, with GSE55235 being used as the validation dataset. The OA and RA data from the GSE1919 dataset were merged with the standardized data from GSE82107 and GSE77298, followed by batch effect removal to obtain the merged datasets of differential expressed genes (DEGs) for OA and RA. Intersection analysis was conducted on the DEGs between the two conditions to identify commonly upregulated and downregulated DEGs. Enrichment analysis was then performed on these common co-expressed DEGs, and a protein-protein interaction (PPI) network was constructed to identify hub genes. These hub genes were further analyzed using the GENEMANIA online platform and subjected to enrichment analysis. Subsequent validation analysis was conducted using the GSE55235 dataset. RESULTS: The analysis of differentially expressed genes in the synovial cells from patients with Osteoarthritis (OA) and Rheumatoid Arthritis (RA), compared to a control group (individuals without OA or RA), revealed significant changes in gene expression patterns. Specifically, the genes APOD, FASN, and SCD were observed to have lower expression levels in the synovial cells of both OA and RA patients, indicating downregulation within the pathological context of these diseases. In contrast, the SDC1 gene was found to be upregulated, displaying higher expression levels in the synovial cells of OA and RA patients compared to normal controls.Additionally, a noteworthy observation was the downregulation of the transcription factor PPARG in the synovial cells of patients with OA and RA. The decrease in expression levels of PPARG further validates the alteration in lipid metabolism and inflammatory processes associated with the pathogenesis of OA and RA. These findings underscore the significance of these genes and the transcription factor not only as biomarkers for differential diagnosis between OA and RA but also as potential targets for therapeutic interventions aimed at modulating their expression to counteract disease progression. CONCLUSION: The outcomes of this investigation reveal the existence of potentially shared molecular mechanisms within Osteoarthritis (OA) and Rheumatoid Arthritis (RA). The identification of APOD, FASN, SDC1, TNFSF11 as key target genes, along with their downstream transcription factor PPARG, highlights common potential factors implicated in both diseases. A deeper examination and exploration of these findings could pave the way for new candidate targets and directions in therapeutic research aimed at treating both OA and RA. This study underscores the significance of leveraging bioinformatics approaches to unravel complex disease mechanisms, offering a promising avenue for the development of more effective and targeted treatments.


Subject(s)
Arthritis, Rheumatoid , Gene Expression Profiling , Osteoarthritis , Protein Interaction Maps , Synovial Membrane , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Humans , Osteoarthritis/genetics , Osteoarthritis/metabolism , Osteoarthritis/pathology , Protein Interaction Maps/genetics , Synovial Membrane/metabolism , Synovial Membrane/pathology , Computational Biology/methods , Gene Regulatory Networks , Gene Expression Regulation , Databases, Genetic
12.
Arch Virol ; 169(5): 117, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38739272

ABSTRACT

Xanthomonas phage AhaSv was isolated from lake water. Genome sequencing showed that its genome is a linear dsDNA molecule with a length of 55,576 bp and a G+C content of 63.23%. Seventy-one open reading frames (ORFs) were predicted, and no tRNAs were found in the genome. Phylogenetic analysis showed that AhaSv is closely related to members of the genus Salvovirus of the family Casjensviridae. Intergenomic similarity values between phage AhaSv and homologous phages were up to 90.6%, suggesting that phage AhaSv should be considered a member of a new species in the genus Salvovirus.


Subject(s)
Bacteriophages , Genome, Viral , Open Reading Frames , Phylogeny , Xanthomonas , Bacteriophages/genetics , Bacteriophages/classification , Bacteriophages/isolation & purification , Base Composition , DNA, Viral/genetics , Lakes/virology , Lakes/microbiology , Sequence Analysis, DNA , Xanthomonas/virology , Xanthomonas/genetics , Xanthomonas/classification
13.
Hypertens Res ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38769138

ABSTRACT

Obesity-related hypertension (OH) is accompanied by obvious endothelial dysfunction, which contributes to increased peripheral vascular resistance and hypertension. Adrenomedullin (ADM), a multifunctional active peptide, is elevated in obese humans. The OH rats induced by high fat diet (HFD) for 28 weeks and the human umbilical vein endothelial cells (HUVECs)-treated by palmitic acid (PA) were used to investigate the effects of ADM on endothelial dysfunction and the underlying mechanisms. Vascular reactivity was assessed using mesenteric arteriole rings, and the protein expression levels were examined by Western blot analysis. Compared with the control rats, OH rats exhibited hypertension and endothelial dysfunction, along with reduced eNOS protein expression and Akt activation, and increased protein expression of proinflammatory cytokines and ROS levels. Four-week ADM administration improved hypertension and endothelial function, increased eNOS protein expression and Akt activation, and attenuated endothelial inflammation and oxidative stress in OH rats. In vitro experiment, the antagonism of ADM receptors with ADM22-52 and the suppression of Akt signaling with A6730 significantly blocked ADM-caused increase of NO content and activation of eNOS and Akt, and inhibited the anti-inflammatory and anti-oxidant effect of ADM in PA-stimulated HUVECs. These data indicate that endothelial dysfunction in OH rats is partially attributable to the decreased NO level, and the increased inflammation and oxidative stress. ADM improves endothelial function and exerts hypotensive effect depending on the increase of NO, and its anti-inflammatory and anti-oxidant effect via receptor-Akt pathway.

14.
Org Lett ; 26(15): 3140-3144, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38563571

ABSTRACT

Carbonylative multifunctionalization of alkenes is an efficient approach to introduce multiple functional groups into one molecule from easily available materials. Herein, we developed an iron-catalyzed radical relay carbonylative cyclization of alkenes with acetamides. Various α-tetralones can be constructed in moderate yields from readily available substrates with an earth-abundant iron salt as the catalyst.

15.
J Int Med Res ; 52(4): 3000605241247683, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38676540

ABSTRACT

Tibial tubercle avulsion fractures (TTAFs) are rare but typical in children and adolescents and Osgood-Schlatter disease (OSD) may be involved in their pathogenesis. However, few publications have reported the relationship between OSD and TTAF. A 16-year-old healthy male adolescent presented with pain, swelling and limited range of motion of the right knee following sudden acceleration while running. Based on the radiographic evidence, the patient was diagnosed with an avulsion fracture of the right tibial tubercle and OSD. Open reduction and internal fixation were performed using two cannulated screws and two Kirschner wires. The patient returned to preinjury activity levels at the 12-month follow-up postoperatively. This case report aimed to highlight this unique injury pattern. For patients with TTAFs, not only should the fracture be treated, but the cause of the fracture, such as OSD, should also be given appropriate treatment.


Subject(s)
Fracture Fixation, Internal , Fractures, Avulsion , Osteochondrosis , Tibial Fractures , Humans , Adolescent , Male , Tibial Fractures/surgery , Tibial Fractures/diagnostic imaging , Fractures, Avulsion/surgery , Fractures, Avulsion/diagnostic imaging , Osteochondrosis/surgery , Osteochondrosis/diagnostic imaging , Fracture Fixation, Internal/methods , Tibia/diagnostic imaging , Tibia/surgery , Tibia/injuries , Tibia/pathology , Bone Screws
16.
Phytochemistry ; 222: 114108, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663825

ABSTRACT

Twelve undescribed 2-(2-phenethyl)chromone dimers (1-12) were isolated from EtOAc extract of agarwood originating from Aquilaria filaria in the Philippines, guided by a UHPLC-MS analysis. Their structures were elucidated by 1D NMR, 2D NMR, and HR-ESI-MS spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by single-crystal X-ray diffraction analysis and comparison of the experimental and calculated ECD spectra. Compounds 1, 2, 5 and 9-12 exhibited potent to moderate anti-inflammatory activity with IC50 values in the range of 22.43 ± 0.86 to 53.88 ± 4.06 µM.


Subject(s)
Chromones , Thymelaeaceae , Wood , Thymelaeaceae/chemistry , Philippines , Chromones/chemistry , Chromones/isolation & purification , Chromones/pharmacology , Molecular Structure , Wood/chemistry , Animals , Structure-Activity Relationship , Mice , Dose-Response Relationship, Drug , Crystallography, X-Ray , Flavonoids
17.
Cell Commun Signal ; 22(1): 230, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627796

ABSTRACT

OBJECTIVE: Recurrent pregnancy loss (RPL) patients have higher absolute numbers of decidual natural killer (dNK) cells with elevated intracellular IFN-γ levels leading to a pro-inflammatory cytokine milieu, which contributes to RPL pathogenesis. The main objective of this study was twofold: first to explore the regulatory effects and mechanisms of villus-derived exosomes (vEXOs) from induced abortion patients or RPL patients at the level of intracellular IFN-γ in dNK cells; second to determine the validity of application of vEXOs in the treatment of unexplained RPL (uRPL) through in vitro experiments and mouse models. METHODS: Exosomes were isolated from villus explants by ultracentrifugation, co-cultured with dNK cells, and purified by enzymatic digestion and magnetically activated cell sorting. Flow cytometry, enzyme-linked immunosorbent assays, and RT-qPCR were used to determine IFN-γ levels. Comparative miRNA analysis of vEXOs from induced abortion (IA) and uRPL patients was used to screen potential candidates involved in dNK regulation, which was further confirmed by luciferase reporter assays. IA-vEXOs were electroporated with therapeutic miRNAs and encapsulated in a China Food and Drug Administration (CFDA)-approved hyaluronate gel (HA-Gel), which has been used as a clinical biomaterial in cell therapy for > 30 years. In vivo tracking was performed using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyaine iodide (DiR) labelling. Tail-vein and uterine horn injections were used to evaluate therapeutic effects of the engineered exosomes in an abortion-prone mouse model (CBA/J × DBA/2 J). Placental growth was evaluated based on placental weight. IFN-γ mRNA levels in mouse placentas were measured by RT-qPCR. RESULTS: IFN-γ levels were significantly higher in dNK cells of uRPL patients than in IA patients. Both uRPL-vEXOs and IA-vEXOs could be efficiently internalized by dNK cells, whereas uRPL-vEXOs could not reduce the expression of IFN-γ by dNK cells as much as IA-vEXOs. Mechanistically, miR-29a-3p was delivered by vEXOs to inhibit IFN-γ production by binding to the 3' UTR of IFN-γ mRNA in dNK cells. For in vivo treatment, application of the HA-Gel effectively prolonged the residence time of vEXOs in the uterine cavity via sustained release. Engineered vEXOs loaded with miR-29a-3p reduced the embryo resorption rate in RPL mice with no signs of systemic toxicity. CONCLUSION: Our study provides the first evidence that villi can regulate dNK cell production of IFN-γ via exosome-mediated transfer of miR-29a-3p, which deepens our understanding of maternal-fetal immune tolerance for pregnancy maintenance. Based on this, we developed a new strategy to mix engineered vEXOs with HA-Gel, which exhibited good therapeutic effects in mice with uRPL and could be used for potential clinical applications in uRPL treatment.


Subject(s)
Abortion, Induced , Abortion, Spontaneous , MicroRNAs , Animals , Female , Humans , Mice , Pregnancy , Abortion, Spontaneous/genetics , Abortion, Spontaneous/metabolism , Decidua/metabolism , Interferon-gamma/metabolism , Killer Cells, Natural , Mice, Inbred CBA , Mice, Inbred DBA , MicroRNAs/genetics , MicroRNAs/metabolism , Placenta/metabolism , RNA, Messenger/metabolism
18.
RSC Adv ; 14(18): 12720-12734, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38645519

ABSTRACT

The microbial agent technology has made significant progress in remediating nitro-aromatic compounds (NACs), such as p-nitrophenol, 2,4-dinitrophenol, and 2,4,6-Trinitrotoluene, in farmland soil over the past decade. However, there are still gaps in our understanding of the bioavailability and degradation mechanisms of these compounds in low-temperature environments. In this review, we provide a comprehensive summary of the strategies employed by cold-adapted microorganisms and elucidate the degradation pathways of NACs pollutants. To further analyze their metabolic mechanisms, we propose using mass balance to improve our understanding of biochemical processes and refine the degradation pathways through stoichiometry analysis. Additionally, we suggest employing 13C-metabolic flux analysis to track enzyme activity and intermediate products during bio-degradation processes with the aim of accelerating the remediation of nitro-aromatic compounds, particularly in cold regions. Through a comprehensive analysis of pollutant metabolic activities and a commitment to the 'One Health' approach, with an emphasis on selecting non-pathogenic strains, the environmental management strategies for soil remediation could be positioned to develop and implement safe and effective measure.

19.
Sci Total Environ ; 927: 172149, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38569970

ABSTRACT

Metalloid co-contamination such as arsenic (As) and antimony (Sb) in soils has posed a significant threat to ecological balance and human well-being. In this study, a novel magnetic graphene-loaded biochar gel (FeBG) was developed, and its remediation potential for the reclamation of AsSb spoiled soil was assessed through a six-month soil incubation experiment. Results showed that the incorporation of iron substances and graphene imparted FeBG with enhanced surface characteristics, such as the formation of a new FeO bond and an enlarged surface area compared to the pristine biochar (BC) (80.5 m2 g-1 vs 57.4 m2 g-1). Application of FeBG significantly decreased Na2HPO4-extractable concentration of As in soils by 9.9 %, whilst BC addition had a non-significant influence on As availability, compared to the control. Additionally, both BC (8.2 %) and FeBG (16.4 %) treatments decreased the Na2HPO4-extractable concentration of Sb in soils. The enhanced immobilization efficiency of FeBG for As/Sb could be attributed to FeBG-induced electrostatic attraction, complexation (Fe-O(H)-As/Sb), and π-π electron donor-acceptor coordination mechanisms. Additionally, the FeBG application boosted the activities of sucrase (9.6 %) and leucine aminopeptidase (7.7 %), compared to the control. PLS-PM analysis revealed a significant negative impact of soil physicochemical properties on the availability of As (ß = -0.611, P < 0.01) and Sb (ß = -0.848, P < 0.001) in soils, in which Sb availability subsequently led to a suppression in soil enzyme activities (ß = -0.514, P < 0.01). Overall, the novel FeBG could be a potential amendment for the simultaneous stabilization of As/Sb and the improvement of soil quality in contaminated soils.


Subject(s)
Antimony , Arsenic , Charcoal , Environmental Restoration and Remediation , Graphite , Mining , Soil Pollutants , Antimony/chemistry , Antimony/analysis , Graphite/chemistry , Charcoal/chemistry , Soil Pollutants/analysis , Arsenic/analysis , Environmental Restoration and Remediation/methods , Soil/chemistry
20.
Environ Sci Technol ; 58(19): 8194-8206, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38683689

ABSTRACT

Phenolic compounds are largely emitted from biomass burning (BB) and have a significant potential to form SOA (Phc-SOA). However, the toxicological properties of Phc-SOA remain unclear. In this study, phenol and guaiacol were chosen as two representative phenolic gases in BB plumes, and the toxicological properties of water-soluble components of their SOA generated under different photochemical ages and NOx levels were investigated. Phenolic compounds contribute greatly to the oxidative potential (OP) of biomass-burning SOA. OH-adducts of guaiacol (e.g., 2-methoxyhydroquinone) were identified as components of guaiacol SOA (GSOA) with high OP. The addition of nitro groups to 2,5-dimethyl-1,4-benzoquinone, a surrogate quinone compound in Phc-SOA, increased its OP. The toxicity of both phenol SOA (PSOA) and GSOA in vitro in human alveolar epithelial cells decreased with aging in terms of both cell death and cellular reactive oxygen species (ROS), possibly due to more ring-opening products with relatively low toxicity. The influence of NOx was consistent between cell death and cellular ROS for GSOA but not for PSOA, indicating that cellular ROS production does not necessarily represent all processes contributing to cell death caused by PSOA. Combining different acellular and cellular assays can provide a comprehensive understanding of aerosol toxicological properties.


Subject(s)
Aerosols , Biomass , Phenols , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Phenols/toxicity , Humans , Oxidation-Reduction , Air Pollutants/toxicity
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