Lipid Nanoparticular Codelivery System for Enhanced Antitumor Effects by Ferroptosis-Apoptosis Synergistic with Programmed Cell Death-Ligand 1 Downregulation.

Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role in maintaining intracellular redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due to rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing their cytotoxicity and rendering them less effective. In this study, we combined erastin, a GSH biosynthesis inhibitor, with 2'-deoxy-5-fluorouridine 5'-monophosphate sodium salt (FdUMP), an ROS-based drug, to effectively disrupt intracellular redox homeostasis and reverse chemotherapy resistance. Therefore, efficient ferroptosis and apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, we employed small interfering RNA targeting PD-L1 (siPD-L1) as a third agent to block immune-checkpoint recognition by CD8+ T cells. The highly immunogenic cell peroxidates or damage-associated molecular patterns (DAMPs) induced by erastin acted synergistically with downregulated PD-L1 to enhance the antitumor effects. To codeliver these three drugs simultaneously and efficiently, we designed GE11 peptide-modified lipid nanoparticles (LNPs) containing calcium phosphate cores to achieve high encapsulation efficiencies. In vitro studies verified its enhanced cytotoxicity, efficient intracellular ROS induction and GSH/GPX4 downregulation, substantial lipid peroxidation product accumulation, and mitochondrial depolarization. In vivo, this formulation effectively accumulated at tumor sites and achieved significant tumor inhibition in subcutaneous colon cancer (CRC) mouse models with a maximum tumor inhibition rate of 83.89% at a relatively low dose. Overall, a strategy to overcome clinical drug resistance was verified in this study by depleting GSH and activating adaptive immunity.

Induction Immunochemotherapy Yields a Higher Conversion Rate and Better Overall Survival than Chemotherapy in Initially Unresectable Esophageal Squamous Cell Carcinoma.

INTRODUCTION: This study compared the surgical conversion rate and overall survival (OS) between induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with initially unresectable esophageal squamous cell carcinoma (iuESCC). METHODS: In this multicenter, retrospective cohort study, patients from four high-volume institutions with unresectable diseases were included. The primary endpoints were the conversion surgery rate and OS. A multivariate Cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting was applied to confirm the survival comparison between the iIC and iC cohorts. RESULTS: A total of 309 patients (150 in the iIC cohort and 159 in the iC cohort) were included. A significantly higher conversion surgical rate was observed in the iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P < 0.001). The pathological complete response rates were 22.0% and 5.1% in the iIC and the iC cohorts, respectively (P = 0.001). A significant difference in the OS was observed between the iIC (not reached) and iC cohorts (median 95% CI 36.3 [range 27.2-45.5]). The stabilized inverse probability of treatment weighting yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI 0.102-0.454, P < 0.001) and operation (yes vs. no, HR 0.262, 95% CI 0.161-0.427, P < 0.001) were the significant prognostic factors for OS. CONCLUSIONS: Immunochemotherapy plus conversion surgery in the induction setting may be a better treatment option to achieve high pathological responses and improve OS in iuESCC patients.

Early patient-reported outcomes after robotic-assisted versus video-assisted thoracoscopic lobectomy.

BACKGROUND: Robotic-assisted thoracoscopic surgery (RATS) can achieve traditional clinical outcomes comparable to those of video-assisted thoracoscopic surgery (VATS). However, patient-reported outcomes (PROs) during the early period after RATS and VATS remain unclear. This study aimed to utilize longitudinal electronic PRO (ePRO) assessments to evaluate symptom burden and functional status between these approaches from patients' perspective. METHODS: This study comprised patients who underwent lobectomy via RATS or VATS for non-small cell lung cancer. We collected multiple-time-point PROs data from the prospective longitudinal study via an ePRO system. Symptom severity and function status were assessed using the perioperative symptom assessment for patients undergoing lung surgery and were analyzed between groups using linear mixed-effects models. RESULTS: Of the 164 patients, 42 underwent RATS and 122 underwent VATS. After propensity score matching (PSM), 42 RATS and 84 VATS exhibited similar baseline characteristics. During the 7-day postoperative period, participants underwent RATS reported milder pain (p = 0.014), coughing (p < 0.001), drowsiness (p = 0.001), and distress (p = 0.045) compared with those underwent VATS. Moreover, participants in RATS group showed less functional interference with walking (p < 0.001) and general activity (p < 0.001). RATS exhibited a shorter postoperative hospitalization (p = 0.021) but higher hospital cost (p < 0.001). Meanwhile, short-term clinical outcomes of operative time, dissected lymph node stations, chest tube drainage, and postoperative complication rates were comparable. CONCLUSION: PROs are important metrics for assessing patients' recovery after lobectomy. Compared with VATS, RATS may induce less symptom burden and better functional status for patients in the early postoperative period.

Tumor-derived nanovesicles enhance cancer synergistic chemo-immunotherapy by promoting cGAS/STING pathway activation and immunogenetic cell death.

AIMS: Checkpoint blockade immunotherapy is a promising therapeutic modality that has revolutionized cancer treatment; however, the therapy is only effective on a fraction of patients due to the tumor environment. In tumor immunotherapy, the cGAS-STING pathway is a crucial intracellular immune response pathway. Therefore, this study aimed to develop an immunotherapy strategy based on the cGAS-STING pathway. MATERIALS AND METHODS: The physicochemical properties of the nanoparticles EM@REV@DOX were characterized by TEM, DLS, and WB. Subcutaneous LLC xenograft tumors were used to determine the biodistribution, antitumor efficacy, and immune response. Blood samples and tissues of interest were harvested for hematological analysis and H&E staining. SIGNIFICANCE: Overall, our designed nanovesicles provide a new perspective on tumor immunotherapy by ICD and cGAS-STING pathway, promoting DCs maturation, macrophage polarization, and activating T cells, offering a meaningful strategy for accelerating the clinical development of immunotherapy. KEY FINDINGS: EM@REV@DOX accumulated in the tumor site through EPR and homing targeting effect to release REV and DOX, resulting in DNA damage and finally activating the cGAS-STING pathway, thereby promoting DCs maturation, macrophage polarization, and activating T cells. Additionally, EM@REV@DOX increased the production of pro-inflammatory cytokines (e.g., TNF-α and IFN-ß). As a result, EM@REV@DOX was effective in treating tumor-bearing mice and prolonged their lifespans. When combined with αPD-L1, EM@REV@DOX significantly inhibited distant tumor growth, extended the survival of mice, and prevented long-term postoperative tumor metastasis, exhibiting great potential in antitumor immunotherapy.

Correlation between desynchrony of hippocampal neural activity and hyperlocomotion in the model mice of schizophrenia and therapeutic effects of aripiprazole.

AIMS: The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear. METHODS: Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity. RESULTS: We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment. CONCLUSIONS: These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.

Distinguishing optimal candidates for primary tumor resection in patients with metastatic lung adenocarcinoma: A predictive model based on propensity score matching.

Background: Primary tumor resection is associated with survival benefits in patients with metastatic lung adenocarcinoma (mLUAD). However, there are no established methods to determine which individuals would benefit from surgery. Therefore, we developed a model to predict the patients who are likely to benefit from surgery in terms of survival. Methods: Data on patients with mLUAD were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Depending on whether surgery was performed on the primary tumor, patients were categorized into two groups: cancer-directed surgery (CDS) and no-cancer-directed surgery (No-CDS). Propensity Score Matching (PSM) was utilized to address bias between the CDS and No-CDS groups. The prognostic impact of CDS was assessed using Kaplan-Meier analysis and Cox proportional hazard models. Subsequently, we constructed a nomogram to predict the potential for surgical benefits based on multivariable logistic regression analysis using preoperative factors. Results: A total of 89,039 eligible patients were identified, including 6.4% (5705) who underwent surgery. Following PSM, the CDS group demonstrated a significantly longer median overall survival (mOS) compared with the No-CDS group (23 [21-25] vs. 7 [7-8] months; P < 0.001). The nomogram showed robust performance in both the training and validation sets (area under the curve [AUC]: 0.698 and 0.717, respectively), and the calibration curves exhibited high consistency. The nomogram proved clinically valuable according to decision curve analysis (DCA). According to this nomogram, surgical patients were categorized into two groups: no-benefit candidates and benefit candidates groups. Compared with the no-benefit candidate group, the benefit candidate group was associated with longer survival (mOS: 25 vs. 6 months, P < 0.001). Furthermore, no difference in survival was observed between the no-benefit candidates and the no-surgery groups (mOS: 6 vs. 7 months, P = 0.9). Conclusions: A practical nomogram was developed to identify optimal CDS candidates among patients with mLUAD.

Lipid core-shell nanoparticles co-deliver FOLFOX regimen and siPD-L1 for synergistic targeted cancer treatment.

FOLFOX regimen, composed of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (OXP), has been used as clinical standard therapeutic regimen in treatments of colorectal cancer (CRC) and esophageal squamous cell carcinoma (ESCC). To further improve its therapeutic outcomes, FOLFOX was combined with anti-PD-1 antibody to form an advanced chemo-immune combination strategy, which has been proven more efficient in controlling cancer progression and prolonging patients' survival in various clinical trials. However, bad tumor accumulation, relative high toxicity, numerous treatment cycles with high fees and low compliance as well as drug resistance seriously limit the prognosis of FOLFOX regimen. The "all-in-one" formulations, which could precisely delivery multidrug regimen into tumor sites and cells, showed a promising application prospect for targeted drug delivery as well as reducing side effects. However, the design and preparation of the "all-in-one" formulation with high drug encapsulation efficiencies for all drugs was still challenging. Herein, a lipid core-shell nanoparticle codelivery platform was designed for simultaneous encapsulation of variant FOLFOX composed of miriplatin (MiPt), 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), calcium folinate (CF) and PD-L1 siRNA (siPD-L1) with high efficiencies, and their synergistic anti-tumor mechanisms were studied, respectively. MiPt, a precursor of OXP, was validated capable of inducing efficient immunogenic cell death (ICD) in this work. Additionally, ICD-mediated release of damage associated molecular patterns functionalized synergistically with PD-L1 silence by siPD-L1 to overcome chemoresistance, reverse suppressive tumor microenvironment and recruit more CD8+ T cells. FdUMP, as the intracellular active form of 5-FU, could induce large amounts of reactive oxygen species to enhance the ICD. CF worked as the sensitizer of FdUMP. The enhanced long-term anti-tumor effect of the prepared "all-in-one" formulation compared to free drug regimen and other controls, was verified in heterotopic CRC mice models and ESCC mice models, providing new thoughts for researchers and showing a promising prospect of translation into clinical applications.

CCL2 Knockdown Attenuates Inflammatory Response After Spinal Cord Injury Through the PI3K/Akt Signaling Pathway: Bioinformatics Analysis and Experimental Validation.

Spinal cord injury (SCI) is a common clinical problem in orthopedics with a lack of effective treatments and drug targets. In the present study, we performed bioinformatic analysis of SCI datasets GSE464 and GSE45006 in the Gene Expression Omnibus (GEO) public database and experimentally validated CCL2 expression in an animal model of SCI. This was followed by stimulation of PC-12 cells using hydrogen peroxide to construct a cellular model of SCI. CCL2 expression was knocked down using small interfering RNA (si-CCL2), and PI3K signaling pathway inhibitors and activators were used to validate and observe the changes in downstream inflammation. Through data mining, we found that the inflammatory chemokine CCL2 and PI3K/Akt signaling pathways after SCI expression were significantly increased, and after peroxide stimulation of PC-12 cells with CCL2 knockdown, their downstream cellular inflammatory factor levels were decreased. The PI3K/Akt signaling pathway was blocked by PI3K inhibitors, and the downstream inflammatory response was suppressed. In contrast, when PI3K activators were used, the inflammatory response was enhanced, indicating that the CCL2-PI3K/Akt signaling pathway plays a key role in the regulation of the inflammatory response. This study revealed that the inflammatory chemokine CCL2 can regulate the inflammatory response of PC-12 cells through the PI3K/Akt signaling pathway, and blocking the expression of the inflammatory chemokine CCL2 may be a promising strategy for the treatment of secondary injury after SCI.

Esophageal cancer cell-derived small extracellular vesicles decrease circulating Tfh/Tfr via sEV-PDL1 to promote immunosuppression.

Esophageal cancer (EC) is a deadly malignancy. Small extracellular vesicles (sEVs) with programmed death ligand 1 (sEV-PDL1) induce immune escape to promote tumor progression. Furthermore, the imbalance between circulating follicular helper T (Tfh) and circulating follicular regulatory T (Tfr) cells is related to the progression of many malignant tumors. However, the role of the EC-derived sEV-PDL1 in circulating Tfh/Tfr is unknown. Circulating Tfh and Tfr cells were detected by flow cytometry. sEVs were isolated through differential centrifugation and cultured for cell expansion assays. Naïve CD4+ T cells were isolated, stimulated, and cultured with sEVs to evaluate the frequencies, phenotypes, and functions of Tfh and Tfr cells. The proportion of circulating Tfh in patients with EC was lower than that in healthy donors (HDs), whereas that of circulating Tfr was higher. The EC group showed significantly lower circulating Tfh/Tfr and a higher level of sEV-PDL1 than HDs. Notably, sEV-PDL1 was negatively correlated with circulating Tfh/Tfr in the EC group. In vitro assays, sEV-PDL1 inhibited Tfh expansion, enhanced the cytotoxic T lymphocyte-associated antigen 4+ (CTLA4+) Tfh cell percentage, decreased the levels of interleukin (IL)-21 and interferon-γ, and increased IL-10. sEV-PDL1 promoted the expansion and immunosuppressive functions of circulating Tfr; the increased percentages of CTLA4+ Tfr and inducible T cell co-stimulator+ Tfr were accompanied with high IL-10. However, applying an anti-PDL1 antibody significantly reversed this. Our results suggest a novel mechanism of sEV-PDL1-mediated immunosuppression in EC. Inhibiting sEV-PDL1 to restore circulating Tfh/Tfr balance provides a novel therapeutic approach for EC.

Role of exosomes in prostate cancer bone metastasis.

Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.

Rare sugar L-sorbose exerts antitumor activity by impairing glucose metabolism.

Rare sugars are monosaccharides with low natural abundance. They are structural isomers of dietary sugars, but hardly be metabolized. Here, we report that rare sugar L-sorbose induces apoptosis in various cancer cells. As a C-3 epimer of D-fructose, L-sorbose is internalized via the transporter GLUT5 and phosphorylated by ketohexokinase (KHK) to produce L-sorbose-1-phosphate (S-1-P). Cellular S-1-P inactivates the glycolytic enzyme hexokinase resulting in attenuated glycolysis. Consequently, mitochondrial function is impaired and reactive oxygen species are produced. Moreover, L-sorbose downregulates the transcription of KHK-A, a splicing variant of KHK. Since KHK-A is a positive inducer of antioxidation genes, the antioxidant defense mechanism in cancer cells can be attenuated by L-sorbose-treatment. Thus, L-sorbose performs multiple anticancer activities to induce cell apoptosis. In mouse xenograft models, L-sorbose enhances the effect of tumor chemotherapy in combination with other anticancer drugs. These results demonstrate L-sorbose as an attractive therapeutic reagent for cancer treatment.

SGOL2 promotes prostate cancer progression by inhibiting RAB1A ubiquitination.

Prostate cancer is the most prevalent genitourinary malignant cancer in men worldwide. Patients with prostate cancer who progress to castration-resistant prostate cancer (CRPC) or metastatic CRPC have significantly poorer survival. Advanced prostate cancer is a clinical challenge due to the lack of effective treatment strategies. In the field of oncology, SGOL2 was an emerging and differentially expressed molecule, which enhanced the proliferation of cell populations in vitro in our studies. Mass spectrum and Co-IP validated the interaction of SGOL2 and RAB1A in a protein-protein manner. We further investigated the role of SGOL2 in the regulatory mechanism of RAB1A in prostate cancer cell lines. Furthermore, SGOL2 regulated RAB1A expression by inhibiting its ubiquitination. Rescue Experiments demonstrated that SGOL2 promoted prostate cancer cell proliferation and migration by upregulating RAB1A expression. Finally, we found that SGOL2 and RAB1A may regulate the tumor microenvironment (TME) in prostate cancer. In conclusion, our findings concluded that SGOL2 stabilized RAB1A expression to promote prostate cancer development. Both of them were of great importance in TME modulation.

Thorium(IV) adsorption onto multilayered Ti3C2Tx MXene: a batch, X-ray diffraction and EXAFS combined study.

The interlayer regulation of layered environmental adsorption materials such as two-dimensional early transition metal carbides and carbonitrides (MXenes) plays an important role in their purification performance for specific pollutants. Here the enhanced uptake of ThIV by multilayered titanium carbides (Ti3C2Tx) through a hydrated intercalation strategy is reported. ThIV adsorption behaviors of three Ti3C2Tx samples with different c lattice parameters were studied as a function of contact time, pH, initial concentration, temperature and ion strength in batch experiments. The results indicated that the ThIV uptake was pH and ionic strength dependent, and the adsorption process followed the pseudo-second-order kinetics and the heterogeneous isotherm (Freundlich) model. Thermodynamic data suggested that the adsorption process of all MXene samples was a spontaneous endothermic reaction. The dimethyl sulfoxide intercalated hydrated Ti3C2Tx featured the largest interlayer space and exhibited the highest ThIV adsorption capacity (162 mg g-1 at pH 3.4 or 112 mg g-1 at pH 3.0), reflecting the significant increase in available adsorption sites from Ti3C2Tx interlayers. The adsorption mechanism has been clarified based on adsorption experiments and spectroscopic characterizations. An ion exchange process was proposed for the interaction between hydrated MXenes and ThIV, where H+ from surface [Ti-O]-H+ groups were the primary active sites on Ti3C2Tx. Extended X-ray absorption fine structure (EXAFS) fitting results, in combination with X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses, clearly indicated that ThIV mainly formed the outer-sphere complexes on Ti3C2Tx surface through electrostatic interaction under strong acid conditions, while at pH > 3.0 the adsorption mechanism was determined by inner-sphere coordination and electrostatic interaction together.

Deficiency of the sedoheptulose kinase (Shpk) does not alter the ability of hematopoietic stem cells to rescue cystinosis in the mouse model.

Cystinosis is an autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene encoding the lysosomal cystine transporter, cystinosin, and leading to multi-organ degeneration including kidney failure. A clinical trial for cystinosis is ongoing to test the safety and efficacy of transplantation of autologous hematopoietic stem and progenitor cells (HSPCs) ex vivo gene-modified to introduce functional CTNS cDNA. Preclinical studies in Ctns-/- mice previously showed that a single HSPC transplantation led to significant tissue cystine decrease and long-term tissue preservation. The main mechanism of action involves the differentiation of the transplanted HSPCs into macrophages within tissues and transfer of cystinosin-bearing lysosomes to the diseased cells via tunneling nanotubes. However, a major concern was that the most common cystinosis-causing mutation in humans is a 57-kb deletion that eliminates not only CTNS but also the adjacent sedopheptulose kinase SHPK/CARKL gene encoding a metabolic enzyme that influences macrophage polarization. Here, we investigated if absence of Shpk could negatively impact the efficiency of transplanted HSPCs to differentiate into macrophages within tissues and then to prevent cystinosis rescue. We generated Shpk knockout mouse models and detected a phenotype consisting of perturbations in the pentose phosphate pathway (PPP), the metabolic shunt regulated by SHPK. Shpk-/- mice also recapitulated the urinary excretion of sedoheptulose and erythritol found in cystinosis patients homozygous for the 57-kb deletion. Transplantation of Shpk-/--HSPCs into Ctns-/- mice resulted in significant reduction in tissue cystine load and restoration of Ctns expression, as well as improved kidney architecture comparable to WT-HSPC recipients. Altogether, these data demonstrate that absence of SHPK does not alter the ability of HSPCs to rescue cystinosis, and then patients homozygous for the 57-kb deletion should benefit from ex vivo gene therapy and can be enrolled in the ongoing clinical trial. However, because of the limits inherent to animal models, outcomes of this patient population will be carefully compared to the other enrolled subjects.

Highly efficient adsorption and immobilization of U(VI) from aqueous solution by alkalized MXene-supported nanoscale zero-valent iron.

A novel composite of zero-valent iron nanoparticles supported on alkalized Ti3C2Tx nanoflakes (nZVI/Alk-Ti3C2Tx) was constructed by an in-situ growth method for simultaneous adsorption and reduction U(VI) from aqueous solution in anoxic conditions. The effect of various factors such as adsorbent dose, pH, ionic strength, contact time, initial U(VI) concentration and environmental media were comprehensively investigated by batch experiments. Benefiting from the good dispersion uniformity of nZVI on MXene substrates, nZVI/Alk-Ti3C2Tx exhibited rapid removal kinetics, excellent selectivity, 100% removal efficiency and up to 1315 mg g-1 uptake capacity for U(VI) capture. In the presence of mimic groundwater, 1.0 mM NaHCO3 and 10 mg L-1 humic acid, the removal percentages of U(VI) by the composites could reach 95.1%, 88.9% and 69.5%, respectively. The reaction mechanism between U(VI) and nZVI/Alk-Ti3C2Tx has been clarified based on FTIR, XANES, XPS and XRD analysis. Depending on the consumption of reactive nZVI in the composites and the solution pH, the elimination of U(VI) could be realized by different pathways including reductive immobilization in the form of UO2, inner-sphere surface complexation and hydrolysis precipitation. The present study illustrates that the nZVI/Alk-Ti3C2Tx composite may be an efficient scavenger for radioactive wastewater purification in environmental remediation.

Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia.

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.

Morroniside enhances angiogenesis and improves cardiac function following acute myocardial infarction in rats.

Angiogenesis is critical for re-establishing blood supply to the ischemic myocardium after acute myocardial infarction (AMI). This study aimed to investigate the effects of morroniside on angiogenesis after AMI and explored associated proangiogenic mechanisms. A rat model of AMI was established by ligation of the left anterior descending coronary artery followed by administration of three doses of morroniside. Immunofluorescence staining was performed to identify newly generated endothelial cells and arterioles. The protein expression levels associated with angiogenesis were examined by western blots. Echocardiography was used to examine cardiac function. Our data revealed that morroniside promoted angiogenesis and improved cardiac function in rats with AMI. The proangiogenic effect of morroniside might be mediated by the VEGFA/VEGF receptor 2 signaling pathway.

Efficient removal of uranium from aqueous solution by zero-valent iron nanoparticle and its graphene composite.

Zero-valent iron nanoparticle (ZVI-np) and its graphene composites were prepared and applied in the removal of uranium under anoxic conditions. It was found that solutions containing 24 ppm U(VI) could be completely cleaned up by ZVI-nps, regardless of the presence of NaHCO3, humic acid, mimic groundwater constituents or the change of solution pH from 5 to 9, manifesting the promising potential of this reactive material in permeable reactive barrier (PRB) to remediate uranium-contaminated groundwater. In the measurement of maximum sorption capacity, removal efficiency of uranium kept at 100% until C0(U) = 643 ppm, and the saturation sorption of 8173 mg U/g ZVI-nps was achieved at C0(U) = 714 ppm. In addition, reaction mechanisms were clarified based on the results of SEM, XRD, XANES, and chemical leaching in (NH4)2CO3 solution. Partially reductive precipitation of U(VI) as U3O7 was prevalent when sufficient iron was available; nevertheless, hydrolysis precipitation of U(VI) on surface would be predominant as iron got insufficient, characterized by releases of Fe(2+) ions. The dissolution of Fe(0) cores was assigned to be the driving force of continuous formation of U(VI) (hydr)oxide. The incorporation of graphene supporting matrix was found to facilitate faster removal rate and higher U(VI) reduction ratio, thus benefitting the long-term immobilization of uranium in geochemical environment.

Exploring actinide materials through synchrotron radiation techniques.

Synchrotron radiation (SR) based techniques have been utilized with increasing frequency in the past decade to explore the brilliant and challenging sciences of actinide-based materials. This trend is partially driven by the basic needs for multi-scale actinide speciation and bonding information and also the realistic needs for nuclear energy research. In this review, recent research progresses on actinide related materials by means of various SR techniques were selectively highlighted and summarized, with the emphasis on X-ray absorption spectroscopy, X-ray diffraction and scattering spectroscopy, which are powerful tools to characterize actinide materials. In addition, advanced SR techniques for exploring future advanced nuclear fuel cycles dealing with actinides are illustrated as well.