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1.
Nature ; 604(7907): 723-731, 2022 04.
Article in English | MEDLINE | ID: mdl-35418686

ABSTRACT

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.


Subject(s)
Macaca fascicularis , Transcriptome , Animals , Cell Communication , Macaca fascicularis/genetics , Receptors, Virus/genetics , Transcriptome/genetics , Wnt Signaling Pathway
2.
BMC Neurol ; 24(1): 81, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429754

ABSTRACT

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) are the most prevalent cerebrovascular diseases. The conventional antiplatelet drugs are associated with an inherent bleeding risk, while indobufen is a new antiplatelet drug and has the similar mechanism of antiplatelet aggregation as aspirin with more safety profile. However, there have been no studies evaluating the combination therapy of indobufen and clopidogrel for antiplatelet therapy in cerebrovascular diseases. OBJECTIVE: The CARMIA study aims to investigate the effectiveness and safety of a new dual antiplatelet therapy consisting of indobufen and clopidogrel comparing with the conventional dual antiplatelet therapy consisting of aspirin and clopidogrel in patients with minor ischemic stroke or high-risk TIA. METHODS: An open-label randomized controlled clinical trial was conducted at a clinical center. We randomly assigned patients who had experienced a minor stroke or transient ischemic attack (TIA) within 72 h of onset, or within 1 month if they had intracranial stenosis (IS), to receive either indobufen 100 mg twice daily or aspirin 100 mg once daily for 21 days. For patients with IS, the treatment duration was extended to 3 months. All patients received a loading dose of 300 mg clopidogrel orally on the first day, followed by 75 mg once daily from the second day to 1 year. We collected prospective data using paper-based case report forms, and followed up on enrolled patients was conducted to assess the incidence of recurrent ischemic stroke or TIA, mRS score, NIHSS (National Institutes of Health Stroke Scale) score, and any bleeding events occurring within 3 month after onset. RESULTS: We enrolled 202 patients diagnosed with ischemic stroke or transient ischemic attack. After applying the criteria, 182 patients were eligible for data analysis. Endpoint events (recurrence of ischemic stroke/TIA, myocardial infarction, or death) were observed in 6 patients (6.5%) receiving aspirin and clopidogrel, including 4 (4.3%) with stroke recurrence, 1 (1.1%) with TIA recurrence, and 1 (1%) with death. In contrast, no endpoint events were reported in the indobufen and clopidogrel group (P = 0.029). The group of patients receiving indobufen and clopidogrel exhibited significantly lower modified Rankin Scale (mRS) score. (scores range from 0 to 6, with higher scores indicating more severe disability) compared to the aspirin and clopidogrel group (common odds ratio 3.629, 95% CI 1.874-7.036, P < 0.0001). Although the improvement rate of NIHSS score in the indobufen and clopidogrel group was higher than that in the aspirin and clopidogrel group, the difference was not statistically significant (P > 0.05). Bleeding events were observed in 8 patients (8.6%) receiving aspirin and clopidogrel, including 4 (4.3%) with skin bleeding, 2 (2.2%) with gingival bleeding, 1 (1.1%) with gastrointestinal bleeding, and 1 (1.1%) with urinary system bleeding. On the other hand, only 1 patient (1.1%) in the indobufen and clopidogrel group experienced skin bleeding (P = 0.035). CONCLUSION: The combination of indobufen and clopidogrel has shown non-inferior and potentially superior effectiveness and safety compared to aspirin combined with clopidogrel in patients with minor ischemic stroke and high-risk TIA in the CARMIA study (registered under chictr.org.cn with registration number ChiCTR2100043087 in 01/02/2021).


Subject(s)
Ischemic Attack, Transient , Ischemic Stroke , Isoindoles , Phenylbutyrates , Stroke , Humans , Aspirin , Clopidogrel/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/epidemiology , Ischemic Stroke/drug therapy , Prospective Studies , Stroke/drug therapy , Hemorrhage/chemically induced , Drug Therapy, Combination , Treatment Outcome
3.
J Stroke Cerebrovasc Dis ; 33(5): 107647, 2024 May.
Article in English | MEDLINE | ID: mdl-38431112

ABSTRACT

BACKGROUND: High-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. METHODS: We conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10-20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5-10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FINDINGS: This trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. INTERPRETATION: Compared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.


Subject(s)
Anticholesteremic Agents , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Ischemic Attack, Transient , Ischemic Stroke , Stroke , Male , Humans , Female , Middle Aged , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Ezetimibe/adverse effects , Rosuvastatin Calcium , Atorvastatin , Anticholesteremic Agents/adverse effects , Cholesterol, LDL , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/chemically induced , Stroke/diagnosis , Stroke/drug therapy , Stroke/prevention & control , Ischemic Stroke/drug therapy , Tablets , Drug Therapy, Combination , Treatment Outcome
4.
Environ Sci Technol ; 57(36): 13356-13365, 2023 09 12.
Article in English | MEDLINE | ID: mdl-37653579

ABSTRACT

To understand the nanotoxicity effects on plants, it is necessary to systematically study the distribution of NPs in vivo. Herein, elemental and particle-imaging techniques were used to unravel the size effects of ZnO NPs on phytotoxicity. Small-sized ZnO NPs (5, 20, and 50 nm) showed an inhibitory effect on the length and biomass of rice (Oryza sativa L.) used as a model plant. ZnO NP nanotoxicity caused rice root cell membrane damage, increased the malondialdehyde content, and activated antioxidant enzymes. As a control, the same dose of Zn2+ salt did not affect the physiological and biochemical indices of rice, suggesting that the toxicity is caused by the entry of the ZnO NPs and not the dissolved Zn2+. Laser ablation inductively coupled plasma optical emission spectroscopy analysis revealed that ZnO NPs accumulated in the rice root vascular tissues of the rhizodermis and procambium. Furthermore, transmission electron microscopy confirmed that the NPs were internalized to the root tissues. These results suggest that ZnO NPs may exist in the rice root system and that their particle size could be a crucial factor in determining toxicity. This study provides evidence of the size-dependent phytotoxicity of ZnO NPs.


Subject(s)
Oryza , Zinc Oxide , Particle Size , Zinc Oxide/toxicity , Antioxidants , Biomass
5.
Environ Sci Technol ; 57(21): 8035-8043, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37200099

ABSTRACT

Microplastics (MPs), as a new persistent pollutant, can be emitted and accumulated in urban environments, but there is no detailed information on the driving factors of MP pollution. In this study, through a large-scale wetland soil survey, the features of MPs were characterized in each urban area. The results showed an average abundance to be 379 n/kg in wetland soil. Polypropylene, fiber or fragment, and black color were common composition, shape, and color, respectively. The spatial distribution information showed that MP abundance was significantly relevant to the distance from the urban economic center. Furthermore, the correlation and regression analysis revealed that MP abundance was related to soil heavy metal and atmospheric particle (PM10 and PM2.5) concentrations (P < 0.05), while the promotion of socioeconomic activities (urbanization level, population density, etc.) may aggravate the pollution degree. Additionally, by using structural equation modeling, it was found that the urbanization level was the dominant factor driving the MP pollution degree, with a total effect coefficient of 0.49. Overall, this work provides multi-sided environmental information regarding MP pollution in urban ecosystems, which is significant for follow-up studies of MP pollution control and restoration.


Subject(s)
Microplastics , Water Pollutants, Chemical , Plastics/analysis , Wetlands , Ecosystem , Soil , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis
6.
Nucleic Acids Res ; 48(D1): D118-D126, 2020 01 08.
Article in English | MEDLINE | ID: mdl-31713618

ABSTRACT

Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA-disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA-target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA-target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA-target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA-target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.


Subject(s)
Computational Biology/methods , Databases, Genetic , Gene Expression Regulation , Genomics/methods , RNA Interference , RNA, Long Noncoding/genetics , Software , Genetic Association Studies , Genetic Predisposition to Disease , Humans , User-Computer Interface , Web Browser
7.
FASEB J ; 33(6): 7037-7048, 2019 06.
Article in English | MEDLINE | ID: mdl-30870006

ABSTRACT

The effective therapeutic approach of cerebral infarction is limited because of its underlying complexity. Recently, multiple long noncoding RNAs (lncRNAs) have been identified in the pathogenesis of cerebral infarction. Here, the current study aims to explore the interaction among lncRNA cyclin-dependent kinase inhibitor-2B-antisense RNA 1 (CDKN2B-AS1), transcription factor B-cell lymphoma/leukemia 11A (BCL11A), and MAPKK kinase kinase 1 (MAP4K1) and further investigate whether they affect cerebral infarction progression. The expression of CDKN2B-AS1, BCL11A, and MAP4K1 was altered in lymphocytes extracted from patients with cerebral infarction. In order to identify their roles in regulatory T (Treg) cells, the proliferation and apoptosis of the CD4+CD25+ Treg cells were examined, and levels of IL-4, IL-10, and TGF-ß were determined. Also, the RNA crosstalk among CDKN2B-AS1, BCL11A, and MAP4K1 was validated. Finally, we established a rat model of middle cerebral arterial occlusion to evaluate the neurologic impairment and cerebral infarction volume. The results revealed that lymphocytes in patients with cerebral infarction presented with the up-regulated expression of CDKN2B-AS1. Moreover, BCL11A could specifically bind to CDKN2B-AS1 and MAP4K1 promoter so as to inhibit MAP4K1. Moreover, it was observed that down-regulated CDKN2B-AS1 inhibited CD4+CD25+ Treg-cell proliferation, reduced levels of IL-4, IL-10, and TGF-ß and cerebral infarction volume, and elevated MAP4K1 expression. Collectively, our study provides evidence that CDKN2B-AS1 silencing could increase MAP4K1 expression to inhibit the CD4+CD25+ Treg-cell proliferation by reducing enrichment of transcription factor BCL11A, thereby protecting against cerebral infarction progression, highlighting a promising therapeutic strategy for treating cerebral infarction.-Lei, J.-J., Li, H.-Q., Mo, Z.-H., Liu, K.-J., Zhu, L.-J., Li, C.-Y., Chen, W.-L., Zhang, L. Long noncoding RNA CDKN2B-AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription.


Subject(s)
Protein Serine-Threonine Kinases/metabolism , RNA, Long Noncoding/metabolism , Repressor Proteins/metabolism , Aged , Aged, 80 and over , Animals , Case-Control Studies , Cerebral Infarction , Female , Gene Silencing , Humans , Lymphocytes/metabolism , Male , Middle Aged , Protein Binding , Protein Serine-Threonine Kinases/genetics , RNA, Long Noncoding/genetics , Rats , Repressor Proteins/genetics , T-Lymphocytes, Regulatory/metabolism , Up-Regulation
8.
Int J Biol Macromol ; 267(Pt 2): 131726, 2024 May.
Article in English | MEDLINE | ID: mdl-38688791

ABSTRACT

The characteristics of multi-hydroxyl structure and strong hydrogen bonding in polyvinyl alcohol (PVA) make its melting point close to its decomposition temperature, causing melt-processing difficulty. In this work, following the plasticization of small-molecule primary plasticizer acetamide, lignin was demonstrated as a green secondary plasticizer in realizing the melt processing and simultaneous reinforcement of PVA. During the plasticization process, lignin was able to combine with the hydroxyl groups of PVA, so as to destroy the hydrogen bonds and regularity of the PVA chains. The synergistic plasticization effect of lignin dramatically reduced the melting point of PVA from 185 °C to 151 °C. The thermal processing window of PVA composites was expanded from 50 °C to roughly 80 °C after introducing lignin. In contrast to acetamide, the addition of lignin significantly increased the tensile strength and Young's modulus of the composites to 71 MPa and 1.34 GPa, respectively. Meanwhile, lignin helped to hinder the migration of acetamide via hydrogen bonds. With the addition of lignin, the composites also displayed enhanced hydrophobicity and excellent UV shielding performance. The strategy of synergistic plasticization of lignin provides a feasible basis for the practical application of lignin in melt-processable PVA materials with good comprehensive properties.


Subject(s)
Lignin , Plasticizers , Polyvinyl Alcohol , Tensile Strength , Lignin/chemistry , Polyvinyl Alcohol/chemistry , Plasticizers/chemistry , Hydrogen Bonding , Temperature , Elastic Modulus , Hydrophobic and Hydrophilic Interactions
9.
Int J Biol Macromol ; 271(Pt 2): 132766, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38823742

ABSTRACT

The efficient development and utilization of green biomass-based macromolecule engineering materials are essential for the sustainable development of human civilization. In this study, lignin-based ethylene-propylene-diene-monomer (EPDM) composites with excellent mechanical performance were fabricated using a simple method. The effects of water-insoluble enzymatically hydrolyzed lignin (EL) and alkali lignin (KL) on the mechanical performance of the composites were investigated separately. The results showed that the tensile strength of EPDM reinforced with KL and EL increased to 24.5 MPa and 22.1 MPa, respectively, surpassing that of the carbon black (CB)-reinforced EPDM. After 72 h of thermo-oxidative aging, the retention rates of the tensile strength and elongation at break in the lignin-reinforced EPDM were much better than those formed with pure CB, indicating that lignin significantly improved the thermo-oxidative aging resistance of the composites. In summary, the Zn2+ coordination bonds formed between the interface of EPDM and lignin in lignin/CB/EPDM ternary composites effectively improved the mechanical performance and aging resistance of the composites. This study has significant implications for enhancing the utilization of lignin and green functional polymer materials.


Subject(s)
Lignin , Lignin/chemistry , Tensile Strength , Ethylenes/chemistry , Structure-Activity Relationship , Zinc/chemistry , Oxidation-Reduction , Cross-Linking Reagents/chemistry , Elastomers
10.
J Hazard Mater ; 480: 136223, 2024 Oct 19.
Article in English | MEDLINE | ID: mdl-39437468

ABSTRACT

Microorganisms are crucial for natural remediation of heavy metal pollution in mining areas. The regional survey and process analysis of Mn mine microbes is still limited. We investigated microbial species composition in tailings and adjacent soils of seven typical Mn mining areas in wet mid-subtropical China. The Mn bioavailable content in tailings was 55 times higher than in soils. Compared to soils, the heavy metal pollution in tailings reduced the hydrolase activities and microbial species diversity by 97 % and 38 %, respectively. The co-occurrence network of bacterial and fungal species in tailings was dominated by symbiosis and synergism, and their network complexity was lower than that in soils. Linear discriminant analysis of effect size revealed that Ralstonia, Acidisoma, and Talaromyces were the species most stimulated by Mn pollution because their relative and absolute abundance in tailings was much higher than those in soils (p < 0.001). These key species defined the co-occurrence networks and affected metabolic pathways of microbial communities. Electrical conductivity and its interaction with Mn bioavailability strongly affected tailings microbial key species. This work identified the key species adapted to extreme Mn pollution in tailings, which can be used for bioremediation and maintenance of ecosystem functions in Mn-contaminated soils.

11.
Curr Neurovasc Res ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38994623

ABSTRACT

BACKGROUND: END (Early Neurologic Deterioration) significantly elevates the risk of morbidity and mortality. While numerous studies have investigated END following hemorrhagic transformation post-thrombolysis in acute cerebral infarction research on END without hemorrhagic transformations in patients with acute cerebral infarction due to non-cardiogenic embolism remains scarce. AIM: This study aimed to elucidate the impact of PCSK9 inhibitors on early neurological deterioration (END) in patients with acute non-cardioembolism cerebral infarction without hemorrhagic transformation post-intravenous thrombolysis. Additionally it aimed to identify risk factors associated with END in patients suffering from this type of stroke. OBJECTIVE: The objective of this study is to investigate the effect of PCSK9 inhibitors on early neurologic deterioration (END) in patients with acute non-cardiogenic cerebral infarction without hemorrhagic transformation after intravenous thrombolysis and identify associated risk factors for END in this patient population. METHODS: In this retrospective case-control study the data of consecutive patients who underwent intravenous thrombolysis after AIS (acute ischemic stroke) without hemorrhagic transformation during hospitalization at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University between January 2018 to February 2023 were retrieved and assessed. An increase of >2 in the National Institutes of Health Stroke Scale (NIHSS) within 7 days after admission was defined as END. RESULTS: This study included 250 patients (56 males 22.4%) they were 63.34±12.901 years old. There were 41 patients in the END group and 209 in the non-END group. The usage rate of PCSK9 inhibitors was significantly different between the END group and non-END group (29.268% vs 58.852% P<0.001). The White blood cell count (WBC) and homocysteine levels showed a significant difference between the two groups (all P<0.05). Patients not using PCSK9 inhibitors (OR=0.282 95%CI: 0.127-0.593) and white blood cell count (OR=1.197, 95%CI: 1.085-1.325) were independently associated with END. Receiver-operating characteristic curve analysis suggested that the sensitivity specificity and area under the curve for PCSK9 inhibitors used for END were 88.9%, 80.7% and 0.648 respectively. CONCLUSION: The use of PCSK9 inhibitors can reduce the incidence of early neurological deterioration in patients with acute non-cardioembolism and non-hemorrhagic transformation after intravenous thrombolysis.

12.
Front Mol Neurosci ; 17: 1365978, 2024.
Article in English | MEDLINE | ID: mdl-38660385

ABSTRACT

Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.

13.
iScience ; 27(2): 108780, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38303701

ABSTRACT

Somatic mutations contribute to cancer development by altering the activity of enhancers. In the study, a total of 135 mutation-driven enhancers, which displayed significant chromatin accessibility changes, were identified as candidate risk factors for breast cancer (BRCA). Furthermore, we identified four mutation-driven enhancers as independent prognostic factors for BRCA subtypes. In Her2 subtype, enhancer G > C mutation was associated with poorer prognosis through influencing its potential target genes FBXW9, TRIR, and WDR83. We identified aminoglutethimide and quinpirole as candidate drugs targeting the mutated enhancer. In normal subtype, enhancer G > A mutation was associated with poorer prognosis through influencing its target genes ALOX15B, LINC00324, and MPDU1. We identified eight candidate drugs such as erastin, colforsin, and STOCK1N-35874 targeting the mutated enhancer. Our findings suggest that somatic mutations contribute to breast cancer subtype progression by altering enhancer activity, which could be potential candidates for cancer therapy.

14.
Clin Neuropharmacol ; 46(2): 60-65, 2023.
Article in English | MEDLINE | ID: mdl-36790373

ABSTRACT

OBJECTIVES: Intravenous thrombolysis and mechanical endovascular thrombectomy are recommended for patients whose stroke onsets are within the first 6 hours; however, patients beyond this time window have very limited options. Dl-3-n-butylphthalide (NBP) and human urinary kallidinogenase (HUK) have shown potential clinical benefits in the treatment of acute ischemic stroke (AIS) patients. This research aims to investigate the efficacy and safety of NBP combined with HUK in the treatment of ischemic stroke patients. PATIENTS AND METHODS: We reviewed the 215 AIS patients registered in the database of the Fifth Affiliated Hospital of Sun Yat-sen University from April 2019 to October 2020. Among them, 65 patients received NBP sodium chloride injection treatment, 55 patients received HUK treatment, and 95 patients received NBP sodium chloride injection combined with HUK treatment. The recovery of neural function was evaluated by the National Institutes of Health Stroke Scale (NIHSS), and the recovery of daily function was evaluated by the modified Rankin Scale (mRS). The NIHSS and mRS scores after the 7-day treatment, 6-month independency rate (6-month mRS score ≤1), and related factors were compared among the 3 groups. The safety was monitored by recording adverse events. RESULTS: The NIHSS and mRS scores of 7-day and 6-month treatment in the NBP combined with HUK group were lower than the monotherapy ( P < 0.05). In addition, the NBP combined with HUK treatment achieved an independency rate of 82.1%, whereas NBP and HUK treatments achieved only 53.8% and 63.6%, respectively ( P < 0.001). Binary logistic regression showed that NBP combined with HUK therapy treatment could lead to a 5.28 times higher rate of patients' 6-month independency after AIS occurrence. No serious adverse events occurred in both the combined therapy and monotherapy. CONCLUSIONS: Dl-3-n-butylphthalide combined with HUK is safe to treat AIS patients. It can significantly improve the neural function and the 6-month recovery of AIS patients.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Brain Ischemia/drug therapy , Sodium Chloride/therapeutic use , Stroke/drug therapy , Tissue Kallikreins/therapeutic use , Treatment Outcome
15.
Plants (Basel) ; 12(13)2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37447011

ABSTRACT

Agroforest systems have been widely recognized as an integrated approach to sustainable land use for addressing the climate change problem because of their greater potential to sequester atmospheric CO2 with multiple economic and ecological benefits. However, the nature and extent of the effects of an age-sequence of agroforestry systems on carbon (C) storage remain largely unknown. To reveal the influence of different aged poplar-crop systems on C stocks, we investigated the variation in biomass and C storage under four aged poplar-crop agroforest systems (3-, 9-, 13-, and 17-year-old) in the Henan province of China. The results showed that stand biomass increased with forest age, ranging from 26.9 to 121.6 t/ha in the corresponding four aged poplar-crop systems. The poplar tree biomass accounted for >80% of the total stand biomass in these poplar-crop agroforestry systems, except in the 3-year-old agroforestry system. The average stand productivity peaked in a 9-year-old poplar-crop system (11.8 t/ha/yr), the next was in 13- and 17-year-old agroforestry systems, and the minimum was found in 3-year-old poplar-crop stands (4.8 t/ha/yr). The total C stocks increased, with aging poplar-crop systems ranging from 99.7 to 189.2 t/ha in the studied agroforestry systems. The proportion of C stocks accounted for about 6, 25, and 69% of the total C stocks in the crop, poplar tree, and soil components in all studied agroforestry ecosystems, respectively. Our results suggested that the poplar-crop system, especially in productive and mature stages, is quite an effective agroforestry model to increase the study site's biomass production and C stocks. This study highlighted the importance of agroforestry systems in C storage. It recommended the poplar-crop agroforest ecosystems as a viable option for sustainable production and C mitigation in the central region of China.

16.
Chemosphere ; 340: 139793, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37572714

ABSTRACT

Chromium (Cr) is one of the common environmental pollutants, which causes severe health hazards on human health and environmental security. In this study, we characterized two biochars, a raw biochar (RBC) and a Fe-modified biochar (MBC) made from poplar wood chips and determined the effect of the two biochars on remediation of hexavalent chromium (Cr(VI)) in hydroponic system by monitoring Pak choi growth. Results showed the surface area, pore number and pore volume were significantly higher in MBC than in PBC, but the pore size was larger in PBC than in MBC. When compared to the control, low concentrations of Cr(VI) (≤2 mg L-1) promoted the growth and biomass production of Pak choi by 10-78%. In contrast, the high concentrations of Cr(VI) (≥4 mg L-1) showed a significantly reduction of the growth and biomass production of Pak choi by 10-28%. Fe-modified biochar (MBC) had a more significant impact than RBC on the remediation of Cr in the Cr(VI) pollution and improved growth and biomass production of Pak choi to a greater extent. Our study indicated that MBC has a better effect on degrading Cr(VI) pollution. The findings provide scientific basis and reference for the remediation of heavy metals in aquatic ecosystems by using biochar.


Subject(s)
Seedlings , Water Pollutants, Chemical , Humans , Hydroponics , Ecosystem , Charcoal , Chromium , Adsorption
17.
Plants (Basel) ; 12(17)2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37687293

ABSTRACT

In order to explore the influences of rice straw mulching on soil fertility in agroforestry systems, the soil C and N contents and enzyme activities were investigated in a C. oleifera-cassia intercropping ecosystem in Central Southern China. Three straw mulching application treatments were set up in this study, in 2021, namely, straw powder mulching (SPM), straw segment mulching (SSM), and non-straw mulching as the control (CK). Soil samples were collected from three soil depths (0-10 cm,10-20 cm, and 20-40 cm) in each treatment on the 90th-day after the treatments. The soil organic carbon (SOC), total nitrogen (TN), microbial carbon (MBC), soil enzyme activities (including acid phosphatase (ACP), urease (UE), cellulase (CL), and peroxidase (POD)), and soil water content (SWC) were determined. The results showed that the SOC significantly increased due to the mulching application in SPM and SSM, in the topsoil of 0-10 cm when compared to the CK. The SWC, SOC, TN, and MBC increased by 0.8 and 56.5, 3.5 and 37.5, 21.3 and 61.6, and 5.8% and 76.8% in the SPM and SSM treatments compared to the CK, respectively. The soil enzyme activities of ACP, UE, CE, and POD increased significantly due to straw mulching compared with CK throughout all soil layers. The soil enzyme activities of CL and POD were significantly higher in SSM than in SPM across the soil depth except for ACP. The enzyme activities of ACP were 14,190, 12,732, and 6490 U/g in SSM, SPM, and control, respectively. This indicated that mulching application enhanced the enzyme activity of ACP. Mulching had no significant effects on UE and CL, while the POD decreased significantly in the order of SPM > SSM > CK across all soil layers, being, on average, 6.64% and 3.14% higher in SSM and SPM, respectively, compared to the CK plots. The SOC and MBC were the key nutrient factors affecting the soil enzyme activities at the study site. The results from this study provided Important scientific insights for improving soil physicochemical properties during the management of the C. oleifera intercropping system and for the development of the C. oleifera industry.

18.
Plants (Basel) ; 12(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37653848

ABSTRACT

Forests undergo a long-term development process from young to mature stages, yet the variations in soil nutrients, enzyme activities, microbial diversity, and community composition related to forest ages are still unclear. In this study, the characteristics of soil bacterial and fungal communities with their corresponding soil environmental factors in the young, middle, and mature stages (7, 15, and 25-year-old) of Chinese fir plantations (CFP) in the subtropical region of China were investigated in 2021. Results showed that the alpha diversity indices (Chao1 and Shannon) of soil bacteria and fungi were higher in 15 and 25-year-old stands than in 7-year-old stand of CFP, while the soil pH, soil water content, soil organic carbon, total nitrogen, total phosphorus, sucrase, urease, acid phosphatase, catalase, and microbial biomass carbon, nitrogen, and phosphorus showed higher in 7-year-old stand than other two stands of CFP. The nonmetric multidimensional scaling analysis revealed that the soil microbial species composition was significantly different in three stand ages of CFP. The redundancy and canonical correspondence analysis indicated that the soil urease and microbial biomass nitrogen were the main factors affecting soil bacterial and fungal species composition. Our findings suggested that soil microbial diversity and community structure were inconsistent with changes in soil nutrients and enzyme activities during CFP development, and enhancing stand nurturing and soil nutrient accumulation in the mid-development stage were beneficial to the sustainable management of CFP.

19.
Sci Total Environ ; 856(Pt 1): 159058, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36179836

ABSTRACT

The increased emission and accumulation of micro- or nanoplastics (M-NPs) have posed a severely threaten to organisms in the environment. Though the toxicity of M-NPs has been observed in many species, the fundamental factors determining the biotoxicity are rarely expounded on. In this work, typical polystyrene (PS) M-NPs were set up with a multiparameter variation in size gradient, surface charge contrast and concentration variant, and evaluated by the Caenorhabditis elegans (C. elegans) model. From the endpoints of body length, brood size, survival rate and lifespan, an adverse effect was found on the growth and development of C. elegans caused by PSs. In general, the toxicity of PS was found to be concentrated- and size-dependent, with 100 nm positively charged nano-PS having the highest physio-toxicity. Monitoring by fluorescent imaging, it showed that positively charged nano-PS was mainly ingested and accumulated in the intestinal tract of C. elegans. In addition, the penetrated PS induced severe biological stress reactions with the increase of reactive oxygen species (ROS) and lipofuscin. Furthermore, the following expression of antioxidation-related enzymes was activated in vivo as indicated by the GFP-labelled C. elegans. All the results supplied visually toxic parameters of M-NPs to organisms, which sheds light on the biosecurity and ecological risks of M-NPs in the future.


Subject(s)
Microplastics , Nanoparticles , Animals , Microplastics/toxicity , Caenorhabditis elegans/genetics , Gene Editing , Polystyrenes/toxicity , Coloring Agents
20.
J Hazard Mater ; 447: 130762, 2023 04 05.
Article in English | MEDLINE | ID: mdl-36638676

ABSTRACT

Microplastic threats to biodiversity, health and ecological safety are adding to concern worldwide, but the real impacts on the functioning of organisms and ecosystems are obscure owing to their inert characteristics. Here we investigated the long-lasting ecological effects of six prevalent microplastic types: polyethylene (PE), polypropylene (PP), polyamide (PA), polystyrene (PS), polyethylene terephthalate (PET), and polyvinyl chloride (PVC) on soil bacteria at a 2 % (w/w) level. Due to the inertia and lack of available nitrogen of these microplastics, their effects on bacteriome tended to converge after one year and were strongly different from their short-term effects. The soil volumes around microplastics were very specific, in which the microplastic-adapted bacteria (e.g., some genera in Actinobacteria) were enriched but the phyla Bacteroidetes and Gemmatimonadetes declined, resulting in higher microbial nitrogen requirements and reduced organic carbon mineralization. The reshaped bacteriome was specialized in the genetic potential of xenobiotic and lipid metabolism as well as related oxidation, esterification, and hydrolysis processes, but excessive oxidative damage resulted in severe weakness in community genetic information processing. According to model predictions, microplastic effects are indirectly derived from nutrients and oxidative stress, and the effects on bacterial functions are stronger than on structure, posing a heavy risk to soil ecosystems.


Subject(s)
Microplastics , Plastics , Microplastics/toxicity , Plastics/toxicity , Ecosystem , Soil , Polypropylenes , Bacteria/genetics
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