Prognostic implication and immunotherapy response prediction of a novel ubiquitination-related gene signature in liver cancer.

HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature related to ubiquitination and investigated its correlation with the response to immunotherapy in HCC. The Molecular Signatures Database provided a compilation of genes associated with ubiquitination. A gene signature related to ubiquitination was obtained through Cox regression using the Least Absolute Shrinkage and Selection Operator method. The genetic factors CPY26B1, MCM10, SPINK4, and TRIM54 notably impacted the outcomes of HCC. The patients were divided into two groups: one group had a high risk of poor survival while the other had a low risk but a greater chance of controlling HCC progression. Both univariate and multivariate analyses using Cox regression found the risk score to be an independent predictor of HCC prognosis. Gene set enrichment analysis (GSEA) indicated enrichment in cell cycle and cancer-related microRNAs in high-risk groups. The tumor microenvironment (TME), response to immunotherapy, and effectiveness of chemotherapy medications positively correlated with the risk score. In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.

Tetramethylpyrazine promotes stroke recovery by inducing the restoration of neurovascular unit and transformation of A1/A2 reactive astrocytes.

2,3,5,6-Tetramethylpyrazine (TMP) as an active ingredient extracted from a traditional Chinese herbal medicine Ligusticum chuanxiong Hort. has been proved to penetrate blood-brain barrier (BBB) and show neuroprotective effects on cerebral ischemia. However, whether TMP could regulate astrocytic reactivity to facilitate neurovascular restoration in the subacute ischemic stroke needs to be urgently verified. In this research, permanent occlusion of the middle cerebral artery (MCAO) model was conducted and TMP (10, 20, 40 mg/kg) was intraperitoneally administrated to rats once daily for 2 weeks. Neurological function was evaluated by motor deficit score (MDS). Magnetic resonance imaging (MRI) was implemented to analyze tissue injury and cerebral blood flow (CBF). Magnetic resonance angiography (MRA) was applied to exhibit vascular signals. Transmission electron microscopy (TEM) was performed to detect the neurovascular unit (NVU) ultrastructure. Haematoxylin and eosin (HE) staining was utilized to evaluate cerebral histopathological lesions. The neurogenesis, angiogenesis, A1/A2 reactivity, aquaporin 4 (AQP4) and connexin 43 (Cx43) of astrocytes were observed with immunofluorescent staining. Then FGF2/PI3K/AKT signals were measured by western blot. Findings revealed TMP ameliorated neurological functional recovery, preserved NVU integrity, and enhanced endogenous neurogenesis and angiogenesis of rats with subacute ischemia. Shifting A1 to A2 reactivity, suppressing excessive AQP4 and Cx43 expression of astrocytes, and activating FGF2/PI3K/AKT pathway might be potential mechanisms of promoting neurovascular restoration with TMP after ischemic stroke.

Creating High-Number Defect Sites through a Bimetal Approach in Metal-Organic Frameworks for Boosting Trace SO2 Removal.

Herein, we represent a bimetallic approach to enhance the defect number, leading to eight defect sites per node in a metal-organic framework, showing both a higher SO2 adsorption capacity and higher SO2/CO2 selectivity. The results can be further strongly supported by density functional theory calculations.

SPAG1 promotes the development of AML by activating the ERK/MAPK signaling pathway and affects the chemotherapy sensitivity of venetoclax.

Sperm-associated antigen 1 (SPAG1) is considered to be associated with infertility and tumorigenesis. However, its function in acute myeloid leukemia (AML) remains unclear. In this study, we evaluated the expression level of SPAG1 and explored its clinical prognostic value in patients with AML, as well as its biological function in AML cells. SPAG1 is widely expressed in AML patients, resulting in a poor prognosis. However, its expression was not associated with Fms-related receptor tyrosine kinase 3 (FLT3) mutations. Utilizing the RNA interference knockdown tests, we found that SPAG1 could promote the proliferation and survival of AML cells and regulate the expression of structural maintenance of chromosomes protein 3 (SMC3), activating the ERK/MAPK signaling pathway. Furthermore, we discovered that inhibiting SPAG1 impacted AML cell susceptibility to venetoclax. In conclusion, SPAG1 may serve as a potential therapeutic target in AML.

Magnetic Resonance Imaging Investigation of Neuroplasticity After Ischemic Stroke in Tetramethylpyrazine-Treated Rats.

Ischemic stroke elicits white matter injury typically signed by axonal disintegration and demyelination; thus, the development of white matter reorganization is needed. 2,3,5,6-Tetramethylpyrazine (TMP) is widely used to treat ischemic stroke. This study was aimed to investigate whether TMP could protect the white matter and promote axonal repair after cerebral ischemia. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with TMP (10, 20, 40 mg/kg) intraperitoneally for 14 days. The motor function related to gait was evaluated by the gait analysis system. Multiparametric magnetic resonance imaging (MRI) was conducted to noninvasively identify gray-white matter structural integrity, axonal reorganization, and cerebral blood flow (CBF), followed by histological analysis. The expressions of axonal growth-associated protein 43 (GAP-43), synaptophysin (SYN), axonal growth-inhibitory signals, and guidance factors were measured by Western blot. Our results showed TMP reduced infarct volume, relieved gray-white matter damage, promoted axonal remodeling, and restored CBF along the peri-infarct cortex, external capsule, and internal capsule. These MRI findings were confirmed by histopathological data. Moreover, motor function, especially gait impairment, was improved by TMP treatment. Notably, TMP upregulated GAP-43 and SYN and enhanced axonal guidance cues such as Netrin-1/DCC and Slit-2/Robo-1 but downregulated intrinsic growth-inhibitory signals NogoA/NgR/RhoA/ROCK-2. Taken together, our data indicated that TMP facilitated poststroke axonal remodeling and motor functional recovery. Moreover, our findings suggested that TMP restored local CBF, augmented guidance cues, and restrained intrinsic growth-inhibitory signals, all of which might improve the intracerebral microenvironment of ischemic areas and then benefit white matter remodeling.

Effect of Neurorepair for Motor Functional Recovery Enhanced by Total Saponins From Trillium tschonoskii Maxim. Treatment in a Rat Model of Focal Ischemia.

Trillium tschonoskii Maxim. (TTM), is a perennial herb from Liliaceae, that has been widely used as a traditional Chinese medicine treating cephalgia and traumatic hemorrhage. The present work was designed to investigate whether the total saponins from Trillium tschonoskii Maxim. (TSTT) would promote brain remodeling and improve gait impairment in the chronic phase of ischemic stroke. A focal ischemic model of male Sprague-Dawley (SD) rats was established by permanent middle cerebral artery occlusion (MCAO). Six hours later, rats were intragastrically treated with TSTT (120, 60, and 30 mg/kg) and once daily up to day 30. The gait changes were assessed by the CatWalk-automated gait analysis system. The brain tissues injuries, cerebral perfusion and changes of axonal microstructures were detected by multimodal magnetic resonance imaging (MRI), followed by histological examinations. The axonal regeneration related signaling pathways including phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/collapsin response mediator protein-2 (CRMP-2) were measured by western blotting. TSTT treatment significantly improved gait impairment of rats. MRI analysis revealed that TSTT alleviated tissues injuries, significantly improved cerebral blood flow (CBF), enhanced microstructural integrity of axon and myelin sheath in the ipsilesional sensorimotor cortex and internal capsule. In parallel to MRI findings, TSTT preserved myelinated axons and promoted oligodendrogenesis. Specifically, TSTT interventions markedly up-regulated expression of phosphorylated GSK-3, accompanied by increased expression of phosphorylated PI3K, AKT, but reduced phosphorylated CRMP-2 expression. Taken together, our results suggested that TSTT facilitated brain remodeling. This correlated with improving CBF, encouraging reorganization of axonal microstructure, promoting oligodendrogenesis and activating PI3K/AKT/GSK-3/CRMP-2 signaling, thereby improving poststroke gait impairments.

U-Co Bimetallic-Organic Framework Showing a Helical 1D Pore Decorated by Abundant -CH3 Groups: Robust Nature under Acid, Base, and Water for High-Performance SO2 Removal.

Constructing robust adsorbents for SO2 removal remains a challenging issue. Herein, a U-Co bimetallic-organic framework, namely, ECUT-123, showing a helical 1D pore decorated by abundant -CH3 groups, enables ultrahigh stability under acid, base, and water. This merit further supports its big potential for the removal of trace SO2.

Trillium tschonoskii rhizomes' saponins induces oligodendrogenesis and axonal reorganization for ischemic stroke recovery in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Trillium tschonoskii Maxim. is one of traditional Chinese medical herbs that has been utilized to treat brain damages and cephalalgia. The neuroprotective effect of total saponins from Trillium tschonoskii rhizome (TSTT) has been demonstrated efficacy in rats following ischemia. However, the axonal remodeling effect of TSTT and the detailed mechanisms after ischemic stroke have not been investigated. AIM OF THE STUDY: We aimed to estimate therapeutic role of TSTT in axonal remodeling using magnetic resonance imaging (MRI) technique, and explored possible mechanisms underlying this process followed by histological assays in ischemic rats. METHODS: Male Sprague-Dawley (SD) rats underwent permanently focal cerebral ischemia induced by occluding right permanent middle cerebral artery. TSTT was intragastrically administrated 6 h after surgery and once daily for consecutive 15 days. Neurological function was assessed by the motor deficit score and beam walking test. T2 relaxation mapping and diffusion tensor imaging (DTI) were applied for detecting cerebral tissues damages and microstructural integrity of axons. Luxol fast blue (LFB) and transmission electron microscope (TEM) were performed to evaluate histopathology in myelinated axons. Double immunofluorescent staining was conducted to assess oligodendrogenesis. Furthermore, the protein expressions regarding to axonal remodeling related signaling pathways were detected by Western blot assays. RESULTS: TSTT treatment (65, 33 mg/kg) markedly improved motor function after ischemic stroke. T2 mapping MRI demonstrated that TSTT decreased lesion volumes, and DTI further confirmed that TSTT preserved axonal microstructure of the sensorimotor cortex and internal capsule. Meanwhile, diffusion tensor tractography (DTT) showed that TSTT elevated correspondent density and length of fiber in the internal capsule. These MRI measurements were confirmed by histological examinations. Notably, TSTT significantly increased Ki67/NG2, Ki67/CNPase double-labeled cells along the boundary zone of ischemic cortex and striatum. Meanwhile, TSTT treatment up-regulated the phosphorylation level of Ser 9 in GSK-3ß, and down-regulated phosphorylated ß-catenin and CRMP-2 expression. CONCLUSION: Taken together, our findings indicated that TSTT (65, 33 mg/kg) enhanced post-stroke functional recovery, amplified endogenous oligodendrogenesis and promoted axonal regeneration. The beneficial role of TSTT might be correlated with GSK-3/ß-catenin/CRMP-2 modulating axonal reorganization after ischemic stroke.

Classified Encapsulation of an Organic Dye and Metal-Organic Complex in Different Molecular Compartments for White-Light Emission and Selective Adsorption of C2H2 over CO2.

Encapsulating a certain guest molecule in an assigned molecular compartment and then endowing the corresponding potential remains a huge challenge for metal-organic frameworks. To this end, we demonstrate a good example, for the first time, based on an actinide-based MOF. The used MOF (namely, ECUT-300) shows a unique uranyl-TPE anionic skeleton with three distinct cages, viz., mesopore A (2.8 nm), mesopore B (2.0 nm), and micropore C (0.9 nm). Through solid-liquid reaction, a RhB+ molecule can be encapsulated into ECUT-300 with the exact location in mesopore B, whereas the encapsulation of a metal-organic cation of [Fe(tpy)2]3+ was observed with the location in micropore C, suggesting unprecedented classified encapsulation. Impressively, the potential of the resulting guest@MOF composites is also highly dependent on the type of encapsulated guest molecules, for example, white-light emission for RhB+ and selective adsorption of C2H2 over CO2 for [Fe(tpy)2]3+.

A Robust Cage-Based Metal-Organic Framework Showing Ultrahigh SO2 Uptake for Efficient Removal of Trace SO2 from SO2/CO2 and SO2/CO2/N2 Mixtures.

Removal of trace SO2 from an SO2-containing product is now receiving increasing attention. However, designing a robust porous adsorbent with high SO2 adsorption capacity and good SO2/CO2 selectivity, as well as validity under humid conditions, is still a challenging task. Herein, we report a porous cage-based metal-organic framework, namely ECUT-111, which contains two distinct cages with apertures of 5.4 and 10.2 Å, respectively, and shows high a BET of up to 1493 m2/g and a pore volume of 0.629 cm3/g. Impressively, ECUT-111 enables an ultrahigh SO2 uptake of up to 11.56 mmol/g, exceeding most reported top-performing adsorbents for such a use. More importantly, complete separation of trace SO2 from SO2/CO2 and SO2/CO2/N2 mixtures, especially under humid conditions, and excellent recycle use were observed for ECUT-111, suggesting its superior application in desulfurization of SO2-containing products.

Robust 4d-5f Bimetal-Organic Framework for Efficient Removal of Trace SO2 from SO2/CO2 and SO2/CO2/N2 Mixtures.

Herein, we report a highly rare robust 4d-5f bimetal-organic framework that shows high porosity and thermal/chemical stability and thus is capable of removing trace SO2 from a SO2/CO2/N2 mixture even under humid conditions. This work not only shows a novel adsorbent for SO2 removal but also extends the function of actinium-based coordination compounds.

High Adsorption Capacity and Selectivity of SO2 over CO2 in a Metal-Organic Framework.

Herein, we report a new metal-organic framework (MOF), namely, ECUT-77, which is built on rod-shaped secondary building units, showing a high Brunauer-Emmett-Teller surface area of 760.3 cm2/g, a pore volume of 0.4 cm3/g, and an aperture of about 1 nm. This MOF enables both high SO2 adsorption capacity up to 8.0 mmol/g at 0.92 bar and room temperature and a high SO2/CO2 selectivity of 44, resulting in excellent SO2 separation upon a ECUT-77 column from a SO2/CO2 mixture containing 2000 ppm of SO2.

Prognostic factors and long-term outcomes of eye-globe perforation: Eye injury vitrectomy study.

PURPOSE: To delineate anatomic and visual outcomes of injured eye globes with perforating, and to develop the prognostic indicators for perforating eyes. METHODS: The case series study, from a multicenter prospective cohort database. To the date of December 31st, 2018, of 63 perforating globes were selected. All cases underwent vitreoretinal surgeries or enucleations, and were followed up for at least 6 months. Demographic characteristics, basic examination for traumatized eyes, and intraocular tissue damages were recorded by surgery-in-chief. At the follow-up visit, best corrected VA, intraocular pressure, the intraocular tamponade material, retinal anatomic outcome of eye-globes, and phthisis or enucleation were evaluated. RESULTS: Fifty injured eyes (79%) were caused by sharp objects and 13 eyes (21%) were injured by a missiles. Twenty-two injured eyes can be anatomically restored with final vision of more than 4/200 through vitreoretinal surgery. The PVR-C (OR = 5.67, P = 0.01), area of retinectomy more than 2 times of optic disk (OR = 5.16, P = 0.04), and macular damage (OR = 6.38, P = 0.01) were correlated with unfavorable outcomes. CONCLUSION: The injured eyes with perforation can be saved through vitreoretinal surgery, the PVR-C, retinectomy more than 2 times of optic disk, and macular damage were independent risk factors for poor long-term prognosis.

Traumatic choroidal injuries - classification, incidence, diagnosis and prognosis twenty-year results of Eye Injury Vitrectomy Study.

PURPOSE: To characterize the classification, incidence, diagnosis and prognosis of traumatic choroidal injuries. METHODS: Subjects were selected from the database of the Eye Injury Vitrectomy Study (EIVS) and were examined for occurrences of different categories of choroidal injuries. Standard photographs were collected. Anatomical and visual outcomes were assessed in patients with greater than 1 year of follow-up. Eyes that had no light perception (NLP) and/or phthisis bulbi were defined as having had unfavourable outcomes. The percentage of eyes with an unfavourable outcome was analysed for different types of choroidal injuries. RESULTS: Nine categories of choroidal injuries with distinctive features were identified in the EIVS database. The incidence and the percentage of eyes with an unfavourable outcome in each injury category were as follows: suprachoroidal effusion, 21.2% (7.2%); suprachoroidal haemorrhage, 12.8% (11.2%); massive suprachoroidal haemorrhage, 4.0% (64.9%); choroidal avulsion, 4.2% (92.2%); traumatic chorioretinal rupture, 1.8% (13.3%); choroidal rupture, 4.8% (6.8%); choroidal loss, 1.6% (79.3%); choroidal hole, 1.1% (5.3%); and choroidal damage at the wound site, 39.2% (17.7%). CONCLUSIONS: Ocular trauma can cause a variety of choroidal injuries that have distinctive features, some of which are associated with a high frequency of unfavourable prognoses.

The three-phase enriched environment paradigm promotes neurovascular restorative and prevents learning impairment after ischemic stroke in rats.

Enriched environment (EE) with a complex combination of sensorimotor, cognitive and social stimulations has been shown to enhance brain plasticity and improve recovery of functions in animal models of stroke. The present study extended these findings by assessing whether the three-phase EE intervention paradigm would improve neurovascular remodeling following ischemic stroke. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). A three-phase EE intervention paradigm was designed in terms of the different periods of cerebral ischemia by periodically rearranging the EE cage. Morris water maze (MWM) tests were performed to evaluate the learning and memory function. Multimodal MRI was applied to examine alterations to brain structures, intracranial vessels, and cerebral perfusion on the 31st day after MCAO. The changes of capillaries ultrastructure were examined by transmission electron microscope. Double-immunofluorescent staining was used to evaluate neurogenesis and angiogenesis. The expression of angiogenesis-related factors and neurovascular remodeling related signaling pathways including Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3 (GSK-3)/ß-catenin and the axon guidance molecules were detected by Western blot analysis. MRI measurements revealed that EE treatment significantly increased survival volume of cortex and striatum, improved cerebral blood flow (CBF), amplified anterior azygos cerebral artery (azACA), ipsilateral internal carotid artery (ICA) and anterior communicating artery (AComA) vessel signal compared with standard housed rats (IS). Consistent with these findings, EE reduced ischemic BBB damage of capillary, enhanced endogenous angiogenesis and modified the expression of VEGF, Ang-1 or Ang-2 in ischemic rats. Additionally, this proangiogenic effect was consistent with the increased progenitor cell proliferation and neuronal differentiation in the peri-infarct cortex and striatum after EE intervention. Specifically, EE intervention paradigm markedly increased expression of phosphorylated PI3K, AKT and GSK-3, but reduced phosphorylated ß-catenin. Moreover, the axon guidance proteins expression level was significant higher in EE group. In parallel to these findings, EE significantly enhanced recovery of lost spatial learning memory function in MCAO rats without affecting infarct size. Together, MRI findings along with histological results strongly supported that the three-phase EE paradigm benefited neurovascular reorganization and thereby improved poststroke cognitive function. Moreover, our findings suggest that this type of EE paradigm induced neurogenesis and angiogenesis, at least in part, via regulating PI3K/AKT/GSK-3/ß-catenin signaling pathway and activation of the intrinsic axonal guidance molecules in animal models of ischemic stroke.

General Approach for Constructing Mechanoresponsive and Redox-Active Metal-Organic and Covalent Organic Frameworks by Solid-Liquid Reaction: Ferrocene as the Versatile Function Unit.

We report for the first time the construction of mechanoresponsive and redox-active metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) by anchoring ferrocene (Fc) pendants as mechanophores in the pore wall. This work outlines a simple, general, and low-cost route to tailor MOFs and COFs by a Fc unit for mechanoresponsive nature, the release of Fe ions, redox behavior, and modulation of the skeleton charge together.

Effect of intravitreal ranibizumab pretreatment on vitrectomy in young patients with proliferative diabetic retinopathy.

BACKGROUND: Younger patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) display more aggressive nature distinguished from the older patients. Preoperative anti-VEGF therapy has been widely used as an adjunct for PDR surgery. However, the effect of anti-VEGF administration in young diabetics has rarely been evaluated in previous studies. The purpose of this study was to evaluate the effects of ranibizumab pretreatment on vitrectomy surgery in young patients with PDR. METHODS: This was a prospective nonrandomized comparative study. Young patients (<40 years old) undergoing diabetic vitrectomy with or without ranibizumab pretreatment (25 eyes in each group) were analyzed in this study. The use of the drug was determined by the patients' own preference. The two surgical groups were matched according to a complexity score. Intravitreal injection of ranibizumab (IVR) was performed 3-5 days prior to the vitrectomy surgery in the IVR group. Intraoperative records including total surgical time, intraoperative bleeding, the use of endodiathermy, the frequency of relaxing retinotomies, the incidence of iatrogenic retinal breaks, and the use of perfluorocarbon liquid (PFCL) and silicone oil tamponade, and postoperative indices regarding recurrent vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, and visual outcome were evaluated between the two groups. All patients were followed up for one year after surgery. RESULTS: In young PDR patients, the severity of intraoperative bleeding was significantly lower in the IVR group than in the control group (P=0.04). The total surgical time was shorter in the IVR group than in the control group. However, the rate of relaxing retinotomy, the incidence of iatrogenic retinal breaks and the use of PFCL and silicone oil tamponade were not affected by IVR pretreatment but affected by the complexity score of the case. Early postvitrectomy hemorrhage occurred less frequently in the IVR group than in the control group (P<0.001), Early visual recovery was better in the IVR group than in the control group (P=0.03). However, there were no significant differences in the development of late recurrent VH, NVG, recurrent retinal detachment, and final visual outcome. CONCLUSIONS: IVR pretreatment is a safe and effective adjunct to vitrectomy in reducing intraoperative and early postvitrectomy bleeding and should be suggested in young PDR patients. However, IVR does not reduce the incidence of intraoperative and late postoperative complications in these patients. The risk of iatrogenic retinal breaks and silicone oil use are closely correlated with the complexity score of the surgical cases.

Ultralow-Content Iron-Decorated Ni-MOF-74 Fabricated by a Metal-Organic Framework Surface Reaction for Efficient Electrocatalytic Water Oxidation.

Transition-metal-organic frameworks (MOFs) have been regarded as one of the most intriguing electrocatalysts because of its low cost and diversity in functional organic groups and metal centers. Different from the common strategies of tuning the ratio of metal centers in multivariate MOFs, here, ultralow-content Fe2O3 is decorated on the surface of monometallic Ni-MOF-74 based on the fast "phenol-iron (Fe)" surface reaction between Fe2+ and the surface hydroxyl group in Ni-MOF-74. Benefiting from this flexible method, the Fe loading can be finely modulated and thus a series of Fe-decorated Ni-MOF-74 with different Fe contents are prepared. The optimized 0.6 wt % Fe2O3@Ni-MOF-74 with the Fe loading of 0.6 wt % only needs the overpotential of 264 mV to deliver 10 mA cm-2, which obviously outperforms Fe-free Ni-MOF-74 (323 mV) and other Fe2O3@Ni-MOF-74 and is even superior to the commercial IrO2 benchmark (300 mV). X-ray photoelectron spectroscopy results disclose that Fe decoration can obviously modulate the electronic structure of Ni center in Ni-MOF-74, thereby resulting in enhanced oxygen evolution reaction activity. This work opens up a new avenue to fabricate excellent MOF-based electrocatalysts for direct utilization in an electrocatalytic process.

An MRI Study of Neurovascular Restorative After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Stroke.

Xiaoshuan enteric-coated capsule (XSEC) is a Chinese medicinal compound widely used for treatment of ischemic cerebrovascular diseases. Enriched environment (EE) is an effective rehabilitative protocol designed to enhance sensorimotor, cognitive and social stimulation. This study aimed to apply magnetic resonance imaging (MRI) to non-invasively assess whether EE could augment the therapeutic benefits of XSEC on post-ischemic neurovascular remodeling. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with XSEC and EE alone or combination for 30 consecutive days. Beam walking test and Morris water maze (MWM) test were performed to evaluate motor and cognitive function, respectively. Multimodal MRI was applied to examine alterations to brain structures, intracranial vessels, and cerebral perfusion on the 31st day after MCAO. Double-immunofluorescent staining was used to evaluate neurogenesis and angiogenesis. Western blot and RT-PCR were used to detect the expressions of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the axon guidance molecules. Combination therapy with XSEC and EE significantly reduced cystic volume compared with XSEC and EE monotherapies. In line with this, combination treated rats performed better in the beam walking test and exhibited improved spatial memory in the probe trial of the MWM. Moreover, XSEC and EE combination treatment improved cerebral blood flow (CBF), amplified angiogenesis and upregulated VEGF protein levels. This proangiogenic effect was consistent with the increased progenitor cell proliferation and neuronal differentiation in the peri-infarct cortex and striatum. Specifically, the combined therapy of XSEC and EE markedly increased the Netrin-1 and Robo-1 protein expression levels compared with vehicle group, while no difference was observed between XSEC or EE monotherapy and vehicle group. Together, these findings indicate that the combination of XSEC and EE benefits neurovascular reorganization. This correlates with restoration of CBF, promotion of neurogenesis and angiogenesis, and activation of the intrinsic axonal guidance molecules, thereby facilitating greater physical rehabilitation after ischemic stroke.