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1.
J Colloid Interface Sci ; 558: 323-333, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605934

RESUMO

For the development of metal-air batteries and fuel cells, highly efficient and inexpensive electrocatalysts are one of the main issues for scalable applications of these advanced energy devices. Herein, based on the in situ conversion of FeS to γ-FeOOH with a two-dimensional (2D) layered structure, a special nanohybrid, N, S co-doped porous carbon nanosheets loaded with γ-FeOOH, is fabricated by carbonization of Fe3+-coordinated polydopamine, which uniformly coats the surface of bacterial cellulose. The nanocomposites exhibit high activity towards the cathodic oxygen reduction reaction (ORR), characterized by a more positive half-wave potential (10 mV) than the commercial Pt/C (20 wt%) electrocatalyst in alkaline medium. Additionally, the nanohybrid has excellent stability and a high methanol tolerance towards the ORR. Further experiments and density functional theory (DFT) calculations demonstrate that the doped N, S in the carbon matrix and the (0 1 0) plane of γ-FeOOH are the ORR active sites. A zinc-air battery equipped with this nanohybrid presents better a power density (92 mW cm-2) and specific capacity (740 mA h g-1) than the Pt/C electrocatalyst, demonstrating its promising potential for application in energy conversion devices.

2.
Ecotoxicol Environ Saf ; 188: 109906, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31708226

RESUMO

Despite the toxicity of mercury for mammal has been widely studied in recent years, little is known on its impact on the soil microbiome. In this paper, the effects of mercury in soils microbial communities along a gradient of contamination from no to high concentration was assessed by the richness and diversity of microbial community using high throughput sequencing method. The richness of microbial community decreased gradually with the increase of culture time, while the low and medium concentration of mercury had little effect on the evenness of soil microbial community. Proteobacteria tolerated the mercury contamination, while Acidobacteria, Planctomycetes and Chloroflexi were sensitive to mercury pollution in phylum level. Omnitrophica and Ignavibacteriae microorganisms were very sensitive to mercury contamination and dead quickly when contaminated with mercury. Mercury contamination selected two mercury tolerance genuses which were Massilia and Burkholderia in genus level and at least 22 microorganisms such as Alkanindiges, Geothrix, Polycyclovorans and Sporichthya in genus which mainly from the Acidobacteria, Proteobacteria, Bacteroides, Chloroflexi and Omnitrophica phylum were sensitive to mercury. The bacteria tolerant to mercury in soil were Massilia and Burkholderia from Betaproteobacteria and Lysobacter, Luteimonas from Gammaproteobacteria, separately, they were Gram-negative bacteria with thin cell walls and complex ingredients that responded quickly to pollution stress.

3.
Biomed Pharmacother ; 121: 109659, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31739161

RESUMO

Costunolide, an active sesquiterpene lactone, is derived from a number of medicinal plants and it exhibits a broad spectrum of bioactivities such as anti-inflammatory and potential anti-tumor activity. However, its effects on human osteosarcoma and the underlying mechanisms have not yet been evaluated. Here, we found Costunolide inhibits STAT3 transcriptional activity and the expression level of phospho-STAT3 (Tyr-705). Furthermore, we found Costunolide suppresses STAT3 downstream target genes expression. Finally, our data demonstrated Costunolide inhibits osteosarcoma growth and metastasis in vitro and in vivo. Therefore, our studyprovided the first evidence that Costunolide inhibits osteosarcomagrowth and metastasis by impairing STAT3 signal pathway and Costunolide is a potential candidate in osteosarcoma therapy.

4.
J Cell Biochem ; 121(1): 299-312, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31190436

RESUMO

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has been gradually considered as one of the major pathways that causes the production of interstitial myofibroblasts in diseased kidneys. MATERIALS AND METHODS: The study was done to investigate the effect of a bone marrow stromal cell (BMSCs) transplant on rat podocytes and diabetic nephropathy (DN) rats in high-glucose concentration, and to explore the effect of miR-124a on BMSC therapy. High glucose-injured podocytes and streptozotocin-induced DN rats have been respectively used as injury models in in vitro and in vivo studies. Podocyte viability was measured using the Cell Counting Kit-8 assay. Renal pathological examination was observed by HE staining and Masson staining. The messenger RNA and protein levels were determined via real-time polymerase chain reaction and Western blotting, respectively. RESULTS: By mediating the activation of caveolin-1 (cav-1) and ß-catenin and affecting the expression levels of EMT biomarkers including p-cadherin, synaptopodin, fibroblast-specific protein-1, α-smooth muscle actin and snail, our in vitro study confirmed that miR-124a played a significant role in the treatment of high glucose-induced podocyte injury by BMSCs. The therapeutic effects of the BMSC transplant on DN rats were also proved to be further enhanced by miR-124a overexpression in BMSCs, and such a phenomenon was accompanied by the improvement of renal fibrosis and mitigation of DN-related kidney impairment. Regulation of fibronectin, collagen1, and EMT-related proteins was closely implicated with the mechanism, and the activation of cav-1 and ß-catenin was also possibly involved. CONCLUSION: The study demonstrated the pivotal effect of miR-124a on BMSC therapy for DN rats via mitigating EMT and fibrosis. Our results provide a novel insight into how therapeutic effects of BMSCs can be improved at the posttranscriptional level.

5.
Sci Total Environ ; 700: 134502, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31693950

RESUMO

Organophosphate (OP) esters are emerging environmental contaminants, but little is known about their occurrence in dust. In this study, 19 OP triesters and their 11 diester degradation products were measured in indoor dust and outdoor dust collected from China. ∑OP triester concentrations in indoor dust (median: 2380 ng/g dry weight [dw]) were an order of magnitude higher than those in outdoor dust (446 ng/g dw). The median concentrations of ∑OP diesters in indoor and outdoor dust were 260 and 96.8 ng/g dw, respectively. Dust samples collected from eastern and southern China contained higher concentrations of ∑OP di- and tri-esters than those from the other regions. Dust from the most urbanized areas in China including Beijing, Shanghai, and Guangzhou exhibited the highest concentrations of ∑OP di- (>1000 ng/g dw) and triesters (>4000 ng/g dw). We also found notable concentrations of emerging aryl-OP triesters in dust (3.85-10.6 ng/g dw). Significant correlations existed between the concentrations of bis(2-ethylhexyl) phosphate (BEHP) and tris(2-ethylhexyl) phosphate (TEHP) (rho = 0.672-0.691, p < 0.01), as well as DPHP and triphenyl phosphate (TPHP) (rho = 0.537-0.766, p < 0.01) in dust samples, indicating that OP diesters originated from the degradation of triesters. High molar concentration ratios of DEP to triethyl phosphate (TEP) and DPHP to TPHP/ethylhexyl diphenyl phosphate (EHDPP) suggested that these OP triesters degrade readily. Significant correlations were found between the concentrations of ∑OP di- (R2 = 0.390, p < 0.05) and tri-esters (R2 = 0.475, p < 0.01) in paired indoor-outdoor dust samples, which suggested that indoor dust was the source of OP esters to the outdoor environment. The estimated daily intake (EDI) of ∑OP diesters through dust ingestion was 0.21 ng/kg bw/d for adults and 2.59 ng/kg bw/d for children. The exposure levels of OP diesters, DEP and DPHP, were comparable to those of their parent triester compounds.

6.
Bioorg Med Chem Lett ; 30(1): 126662, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31784322

RESUMO

Starting from easy accessible pyrazoletetrahydropyran acetals, a series of new pyrazolone spirocyclohexadienone derivatives were synthesized and assayed for antitumor activity. Compound 10s was identified to possess good antitumor activity. It could induce MDA-MB-231 cancer cell apoptosis in a concentration dependent manner and arrest the cell cycle progression mainly at the G1 phase.

7.
J Hazard Mater ; 382: 121084, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31473514

RESUMO

A native laccase (Lac-Q) with robust cold-adapted and thermostable characteristics from the white-rot fungus Pycnoporus sp. SYBC-L10 was purified, characterized, and used in antibiotic treatments. Degradation experiments revealed that Lac-Q at 10.0 U mL-1 coupled with 1.0 mmol L-1 ABTS could degrade 100% of the tetracycline or oxytetracycline (50 mg L-1) within 5 min with a static incubation at 0 °C (pH 6.0). The presence of the Mn2+ ion inhibited the removal rate of tetracycline and oxytetracycline by the Lac-Q-ABTS system, and the presence of Al3+, Cu2+, and Fe3+ accelerated the removal rate of tetracycline and oxytetracycline by the Lac-Q-ABTS system. Furthermore, the growth inhibition of Bacillus altitudinis SYBC hb4 and E. coli by tetracycline antibiotics revealed that the antimicrobial activity was significantly reduced after treatment with the Lac-Q-ABTS system. Finally, seven transformation products of oxytetracycline (namely TP 445, TP 431, TP 413, TP 399, TP 381, TP 367, and TP 351) were identified during the Lac-Q-mediated oxidation process by using UPLC-MS/MS. A possible degradation pathway including deamination, demethylation, and dehydration was proposed. These results suggest that the Lac-Q-ABTS system shows a great potential for the treatment of antibiotic wastewater containing different metal ions at various temperatures.

8.
Sci Total Environ ; 698: 133860, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514029

RESUMO

The correlation between long-term exposure to SRF-EMR and the decline in male fertility is gradually receiving increasing attention from the medical society. While male reproductive organs are often exposed to SRF-EMR, little is currently known about the direct effects of long-term SRF-EMR exposure on the testes and its involvement in the suppression of male reproductive potential. The present study was designed to investigate this issue by using 4G SRF-EMR in rats. A unique exposure model using a 4G smartphone achieved localized exposure to the scrotum of the rats for 6 h each day (the smartphone was kept on active talk mode and received an external call for 1 min over 10 min intervals). Results showed that SRF-EMR exposure for 150 days decreased sperm quality and pup weight, accompanied by testicular injury. However, these adverse effects were not evident in rats exposed to SRF-EMR for 50 days or 100 days. Sequencing analysis and western blotting suggested Spock3 overexpression in the testes of rats exposed to SRF-EMR for 150 days. Inhibition of Spock3 overexpression improved sperm quality decline and alleviated testicular injury and BTB disorder in the exposed rats. Additionally, SRF-EMR exposure suppressed MMP2 activity, while increasing the activity of the MMP14-Spock3 complexes and decreasing MMP14-MMP2 complexes; these results were reversed by Spock3 inhibition. Thus, long-term exposure to 4G SRF-EMR diminished male fertility by directly disrupting the Spock3-MMP2-BTB axis in the testes of adult rats. To our knowledge, this is the first study to show direct toxicity of SRF-EMR on the testes emerging after long-term exposure.

9.
J Colloid Interface Sci ; 559: 13-20, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31606523

RESUMO

Severe "Shuttle effect" and uncontrollable lithium-dendrite growth are ongoing challenges that hinder the practical application of Lithium-sulfur (Li-S) batteries. Herein, a bifunctional separator was modified by Al2O3 and carbon nanotubes (CNTs) via a facile method. Li-S battery assembled with the modified separator shows excellent cycling stability (760.4 mA h g-1 at 0.2 C after 100 cycles) and promising rate performance. The reason is ascribed to synergistic effect of CNTs and Al2O3 double coating layers, the strong physicochemical interaction between Al2O3 and the polysulfides could alleviate the shuttle effect, and the high conductivity of CNTs can facilitate the reaction kinetics of sulfur and its corresponding discharge products, respectively, which can improve the utilization ratio of sulfur. In addition, the double protection layers improve the hardness of the separator, as well as regulate Li+ ion deposition, which can effectively prevent the formation of lithium dendrites, thus the safety of the batteries are significant improved.

10.
Biosens Bioelectron ; 148: 111834, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706175

RESUMO

Efficient platforms for detecting telomerase activity are essential for early tumor monitoring and diagnosis. Herein, an enzyme-free electroanalytical strategy was developed for reliable and highly sensitive telomerase activity assay based on the increased electrochemical signals of methylene blue (MB) catalyzed by well monodisperse Au nanorods (AuNRs). In the presence of dNTPs and telomerase extracts, the assistant DNA 1 in the double stranded DNA can be extended to telomere repeat units (TTAGGG)n, which could form a hairpin structure by telomerase-triggered extension. The assistant DNA 2 was ingeniously dissociated from the double stranded DNA to combine with capture DNA. As a result, a large amount of AuNRs could be anchored on the surface of these sequences and used for electrocatalytic oxidation of MB. The developed biosensor showed a low limit of detection of 8.20 HeLa cells mL-1 and a wide dynamic range from 30 to 1.04 × 107 HeLa cells mL-1 for the determination of telomerase activity, which can provide a new way for telomerase activity assays in early diagnosis for cancers.

11.
J Hazard Mater ; 383: 121130, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31518815

RESUMO

Enhancing the catalytic activity and stability of enzymes is of great importance in the development of green chemical and cost-effective application, with removal of bisphenol A (BPA) as a prominent example. Engineering immobilization carriers and immobilization methods of enzymes endows great potential to achieve above goal. Until now, these reports have focused on employing the metal-organic frameworks (MOFs) to increase the stability and reusability of enzymes, an enhancement in its catalytic activity has yet to be addressed. This work introduced a biomimetic mineralization process for facile synthesis of laccase@HKUST-1 biocomposite under mild condition. By exploiting the activity of laccase@HKUST-1, we demonstrated, for the first time, that the integration of laccase and HKUST-1 containing cofactor Cu2+ ions leaded to 1.5-fold enhancement in the catalytic activity compared with free laccase, which was due to the synergistic enhancement of substrate oxidation. Indeed, the laccase@HKUST-1 biocomposite could function as active biocatalysts under biologically challenging conditions, such as acidic condition, high temperature, organic solvent, and continuous operation. The oxidation of phenols, such as BPA, with laccase@HKUST-1 reached higher catalytic performance than free laccase, and gave 100% degradation efficiency within 4 h. This study provides a feasible method to improve the activity and stability of laccase, which enable completely remove of BPA from the environment.

12.
J Nanosci Nanotechnol ; 20(4): 2018-2024, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492207

RESUMO

Poly(ethylene glycol) (PEG)/poly(ethylene imine) (PEI) modified superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by the thermal decomposition of iron (III) acetylacetonate (Fe(acac)3) in PEG containing PEI. Transferrin (Tf) was employed to functionalize SPIONs. The potential of Tf-SPIONs as brain magnetic resonance (MR) imaging contrast agents was explored by using Kunming mice as an animal model. The in vivo experiments revealed that Tf-SPIONs exhibited an enhanced contrast time as compared with the PEG-SPIONs and PEG/PEI-SPIONs. Tf-SPIONs exhibit promising potential for bioimaging applications because of their advantages of dispersibility in water, low cytotoxicity and long circulation time in blood.

13.
IEEE Trans Image Process ; 29: 15-28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31283506

RESUMO

Video-based human action recognition is currently one of the most active research areas in computer vision. Various research studies indicate that the performance of action recognition is highly dependent on the type of features being extracted and how the actions are represented. Since the release of the Kinect camera, a large number of Kinect-based human action recognition techniques have been proposed in the literature. However, there still does not exist a thorough comparison of these Kinect-based techniques under the grouping of feature types, such as handcrafted versus deep learning features and depth-based versus skeleton-based features. In this paper, we analyze and compare 10 recent Kinect-based algorithms for both cross-subject action recognition and cross-view action recognition using six benchmark datasets. In addition, we have implemented and improved some of these techniques and included their variants in the comparison. Our experiments show that the majority of methods perform better on cross-subject action recognition than cross-view action recognition, that the skeleton-based features are more robust for cross-view recognition than the depth-based features, and that the deep learning features are suitable for large datasets.

14.
Org Biomol Chem ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793612

RESUMO

The condensation of anilines and alkenyl ethers has been demonstrated by employing visible-light photoredox catalysis. The resulting method enables the synthesis of substituted 2-alkylquinolines under mild and simple conditions with good substrate scope and high yields.

15.
BMC Bioinformatics ; 20(1): 626, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31795943

RESUMO

BACKGROUND: In recent years, lncRNAs (long-non-coding RNAs) have been proved to be closely related to the occurrence and development of many serious diseases that are seriously harmful to human health. However, most of the lncRNA-disease associations have not been found yet due to high costs and time complexity of traditional bio-experiments. Hence, it is quite urgent and necessary to establish efficient and reasonable computational models to predict potential associations between lncRNAs and diseases. RESULTS: In this manuscript, a novel prediction model called TCSRWRLD is proposed to predict potential lncRNA-disease associations based on improved random walk with restart. In TCSRWRLD, a heterogeneous lncRNA-disease network is constructed first by combining the integrated similarity of lncRNAs and the integrated similarity of diseases. And then, for each lncRNA/disease node in the newly constructed heterogeneous lncRNA-disease network, it will establish a node set called TCS (Target Convergence Set) consisting of top 100 disease/lncRNA nodes with minimum average network distances to these disease/lncRNA nodes having known associations with itself. Finally, an improved random walk with restart is implemented on the heterogeneous lncRNA-disease network to infer potential lncRNA-disease associations. The major contribution of this manuscript lies in the introduction of the concept of TCS, based on which, the velocity of convergence of TCSRWRLD can be quicken effectively, since the walker can stop its random walk while the walking probability vectors obtained by it at the nodes in TCS instead of all nodes in the whole network have reached stable state. And Simulation results show that TCSRWRLD can achieve a reliable AUC of 0.8712 in the Leave-One-Out Cross Validation (LOOCV), which outperforms previous state-of-the-art results apparently. Moreover, case studies of lung cancer and leukemia demonstrate the satisfactory prediction performance of TCSRWRLD as well. CONCLUSIONS: Both comparative results and case studies have demonstrated that TCSRWRLD can achieve excellent performances in prediction of potential lncRNA-disease associations, which imply as well that TCSRWRLD may be a good addition to the research of bioinformatics in the future.

16.
Sci Total Environ ; : 134498, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31796289

RESUMO

Tris(1,3-dichloro-2-propyl)phosphate (TDCPP) is one of the most widely used organophosphate ester flame retardants. The presence of TDCPP in surface waters and aquatic organisms have been reported worldwide, yet the ecological risk of TDCPP on microalgae is rarely studied. We investigated the biotransformation of TDCPP and its toxicity on the microalga Scenedesmus obliquus using an untargeted metabolomics approach. Exposure to TDCPP resulted in a dose-response decrease of micoalgal biomass. In the presence of microalgae, TDCPP concentration in the media decreased by 25.3-40.6% after 5 days. TDCPP metabolites were identified in the media including hydrolysis and hydroxyl-substituted dechlorination products. A dose-response separation of metabolic profiles of microalgae was observed, with effect seen at the lowest concentration of 10 µg/L tested, which is slightly higher than environmentally relevant concentrations. Differentiated metabolites identified include 52 lipids and 6 polar metabolites. Analysis of altered lipid pathways suggests that microalgal cells reinforce thylakoid membranes (function to protect photosynthesis) by compromising the integrity of plasma membrane (function to protect cellular substances) and extraplastidial cellular membranes. Changes in the polar metabolites might indicate osmotic stress and improved NO signaling after TDCPP exposure. Consistent with perturbation of membrane lipids, further experiment confirmed that exposure to 10 mg/L TDCPP resulted in significant (p < 0.01) plasma membrane damage. This study indicates biotransformation and the membrane damage toxicity mechanism of TDCPP on S. obliquus, demonstrating the usefulness of metabolomics for the toxicity mechanism elucidation of emerging pollutants.

17.
Biol Open ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796423

RESUMO

Cardiac muscle troponin T (Tnnt2) mediates muscle contraction in response to calcium ion dynamics, and Tnnt2 mutations are associated with multiple types of cardiomyopathy. Here, we employed a zebrafish model to investigate the genetic replenishment strategies of using conditional and inducible promoters to rescue the deficiencies in the heart. tnnt2a mutations were induced in zebrafish via the CRISPR/Cas9 technique, and the mutants displayed heart arrest and dilated cardiomyopathy (DCM)-like phenotypes. We first utilized the classic myocardial promoter of the myl7 and TetOn inducible system to restore tnnt2a expression in myocardial tissue in tnnt2a mutant zebrafish. However, this attempt failed to recover normal heart function and circulation, although heart pumping was partially restored. Further analyses via both RNA-seq and immunofluorescence indicated that Tnnt2a, which was also expressed in a novel group of myl7-negative smooth muscle cells on the outflow tract (OFT), was indispensably responsible for the normal mechanical dynamics of OFT. Lastly, tnnt2 expression induced by OFT cells in addition to the myocardial cells successfully rescued heart function and circulation in tnnt2a mutant zebrafish. Together, our results reveal the significance of OFT expression of Tnnt2 for cardiac function and demonstrate zebrafish larva as a powerful and convenient in vivo platform for studying cardiomyopathy and the relevant therapeutic strategies.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31796467

RESUMO

A majority of gastric cancer (GC) cases in China are diagnosed at advanced stages, chiefly due to lack of an established routine nationwide screening program. This study evaluated the effectiveness of a novel screening program for GC. Seven geographical communities were randomly selected, and residents aged 40 to 69 years were screened. Serological tests of Helicobacter pylori antibodies and pepsinogens, and positive family history of GC in first-degree relatives (FDRs), were used to differentiate individuals for further gastroscopic examination and gastric mucosal biopsies. Among 7773 individuals who underwent examination of serum markers, GC was detected in 14 (1.8‰;10 men). The rate in terms of GC cases per 100 gastroendoscopies was 1.6% (14/872), which was greater than 0.87% previously reported. Eleven of 14 patients with GC (78.6%) were FDRs of GC patients. Two-thirds of the subjects with cardia GC were FDRs of individuals with GC rather than cardia GC. Comparative analysis indicated that the GC subjects were significantly more likely to be FDRs of GC patients, in contrast to those without GC. All the individuals with GC were aged ≥50 years. After conducting a reverse analysis, we propose a novel screening program for GC. In conclusions, the populations most vulnerable to GC are those with positive family history of GC in FDRs, male gender, and aged 50 years or older. This screening program using fewer serum markers combined individual risk factors, mainly FDRs, is novel for identification of high-risk individuals for further gastroscopy in detecting early GC.

19.
Chem Biodivers ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797569

RESUMO

(+)- and (-)-Xanchryones F and G ((+)- and (-)-1 and 2) were isolated from the plant Xanthostemon chrysanthus by chiral separation. Compounds 1 and 2 featured a new carbon skeleton with cinnmaoyltriketone-flavone adducts. Their structures with absolute configurations were elucidated by detailed spectroscopic analyses and chemical calculations. The anti-bacterial and anti-inflamatory activities of (+)- and (-)-1 and 2 were evaluated.

20.
Brain Res Bull ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785301

RESUMO

The "oligovascular unit" is a dynamic structural complex composed of endothelial cells (ECs) and oligodendrocyte progenitor cells (OPCs)/oligodendrocytes. By improving the microenvironment of OPCs in the "oligovascular unit" and promoting the proliferation and differentiation of OPCs, both myelination and white matter injury can be repaired. However, it is unclear what characteristic changes occur in the microenvironment of the "oligovascular unit" after preterm white matter injury (PWMI). Here, we demonstrate the changes in the "oligovascular unit" induced by hypoxia-ischemia (HI) and its underlying mechanism in PWMI mice. White matter injury and inhibited production of myelin from OPCs were observed by histopathological staining in HI neonatal mice. We further observed that the proliferation of OPCs and angiogenesis were increased after HI, which is considered the response of the body and cells to HI. HI-induced oligogenesis occurs around the vessels, indicating that "oligovascular units" exist and promote the proliferation and differentiation of OPCs after HI in the short term. We also determined that angiogenesis and oligogenesis induced by HI in the white matter are related to the PI3K/AKT/mTOR pathway. Furthermore, the myelin sheaths were shown to be disordered on the side of the surgery, and the myelin-dense layer was poorly developed at P14 and P28. Different degrees of damage to the vascular ECs and basement membrane on the surgical side were detected beginning at P4, indicating that EC injury is an early phenomenon that subsequently affects oligogenesis. Taken together, our findings indicate that the proliferation of OPCs and angiogenesis in white matter are increased in the early stage of HI involving PI3K/AKT/mTOR pathway activation. Promoting vascular endothelial function and angiogenesis may increase the proliferation and survival of OPCs via the "oligovascular unit," which suggests a potential method to repair injured white matter in the early stage of PWMI.

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