Electronanofiltration Membranes with a Bilayer Charged Structure Enable High Li+/Mg2+ Selectivity.

Achieving separation of lithium and magnesium with similar radii is crucial for the current lithium extraction technology from salt lakes, which usually possess a high lithium-to-magnesium ratio. Herein, we proposed the facile sequential interfacial polymerization (SIP) approach to construct electronanofiltration membranes (ENFMs) with a bilayer charged structure consisting of a high positively charged surface and a negatively charged sublayer. The trimesoyl chloride (TMC) concentration was adjusted to enhance the -COOH content and negative charge of the polyamide sublayer to promote Li+ migration, and then the quaternized polyethylenimine was introduced to the membrane surface by the SIP process to increase the positive charge density on the surface of the ENFMs, which would block the migration of Mg2+ and enhance the Li+/Mg2+ selectivity of the ENFMs. The optimal quaternary-modified ENFMs achieved outstanding selectivity for Li+/Mg2+ (49.85) and high Li+ flux (4.10 × 10-8 mol cm-2 s-1) at a current density of 10 mA cm-2. Moreover, in simulated brines with low lithium concentration and high Mg2+/Li+ ratio, the optimal ENFMs also displayed elevated Li+/Mg2+ selectivity (>45), highlighting the substantial promise of the membranes for practical applications.

Integrative phosphatidylcholine metabolism through phospholipase A2 in rats with chronic kidney disease.

Dysregulation in lipid metabolism is the leading cause of chronic kidney disease (CKD) and also the important risk factors for high morbidity and mortality. Although lipid abnormalities were identified in CKD, integral metabolic pathways for specific individual lipid species remain to be clarified. We conducted ultra-high-performance liquid chromatography-high-definition mass spectrometry-based lipidomics and identified plasma lipid species and therapeutic effects of Rheum officinale in CKD rats. Adenine-induced CKD rats were administered Rheum officinale. Urine, blood and kidney tissues were collected for analyses. We showed that exogenous adenine consumption led to declining kidney function in rats. Compared with control rats, a panel of differential plasma lipid species in CKD rats was identified in both positive and negative ion modes. Among the 50 lipid species, phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC) and lysophosphatidic acid (LysoPA) accounted for the largest number of identified metabolites. We revealed that six PCs had integral metabolic pathways, in which PC was hydrolysed into LysoPC, and then converted to LysoPA, which was associated with increased cytosolic phospholipase A2 protein expression in CKD rats. The lower levels of six PCs and their corresponding metabolites could discriminate CKD rats from control rats. Receiver operating characteristic curves showed that each individual lipid species had high values of area under curve, sensitivity and specificity. Administration of Rheum officinale significantly improved impaired kidney function and aberrant PC metabolism in CKD rats. Taken together, this study demonstrates that CKD leads to PC metabolism disorders and that the dysregulation of PC metabolism is involved in CKD pathology.

Host/microbiota interactions-derived tryptophan metabolites modulate oxidative stress and inflammation via aryl hydrocarbon receptor signaling.

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that induces the expression of a broad range of downstream genes such as cytochromes P450 enzymes and cyclooxygenase-2. Recent research focuses are shifting from AhR activation induced by xenobiotics to its response patterns to physiological ligands that expand our understanding of how endogenous metabolites as ligands to modulate AhR signaling pathway under homeostasis and pathological conditions. With increasing interest in AhR and its endogenous ligands, it would seem advisable to summarize a variety of endogenous ligands especially host/gut microbiota-derived tryptophan metabolites. Mounting evidence has indicated that AhR play a critical role in the regulation of redox homeostasis and immune responses. In this review, we outline the canonical and non-canonical AhR signalling pathway that is mediated by host/gut microbiota-derived tryptophan metabolites. Through several typical endogenous AhR ligands, we investigated the molecular mechanisms of AhR-induced oxidative stress and inflammation in the pathological milieu, including diabetes, diabetic kidney disease and end-stage renal disease. Finally, we summarize and emphasize the limitations and breakthrough of endogenous AhR ligands from host/microbial tryptophan catabolites. This review might provide novel diagnostic and prognostic approach for refractory human diseases and establish new therapeutic strategies for AhR activation.

Graphene Oxide Nanoparticle-Loaded Ginsenoside Rg3 Improves Photodynamic Therapy in Inhibiting Malignant Progression and Stemness of Osteosarcoma.

Osteosarcoma serves as a prevalent bone cancer with a high metastasis and common drug resistance, resulting in poor prognosis and high mortality. Photodynamic therapy (PDT) is a patient-specific and non-invasive tumor therapy. Nanoparticles, like graphene oxide have been widely used in drug delivery and PDT. Ginsenoside Rg3 is a principal ginseng component and has presented significant anti-cancer activities. Here, we constructed the nanoparticles using GO linked with photosensitizer (PS) indocyanine green (ICG), folic acid, and polyethylene glycol (PEG), and loaded with Rg3 (PEG-GO-FA/ICG-Rg3). We aimed to explore the effect of PEG-GO-FA/ICG-Rg3 combined with PDT for the treatment of osteosarcoma. Significantly, we found that Rg3 repressed proliferation, invasion, and migration, and enhanced apoptosis and autophagy of osteosarcoma cells, while the PEG-GO-FA/ICG-Rg3 presented a higher activity, in which NIR laser co-treatment could remarkably increase the effect of PEG-GO-FA/ICG-Rg3. Meanwhile, stemness of osteosarcoma cell-derived cancer stem cells was inhibited by Rg3 and PEG-GO-FA/ICG-Rg3, and the combination of PEG-GO-FA/ICG-Rg3 with NIR laser further significantly attenuated this phenotype in the system. Moreover, NIR laser notably improved the inhibitor effect of PEG-GO-FA/ICG-Rg3 on the tumor growth of osteosarcoma cells in vivo. Consequently, we concluded that PEG-GO-FA/ICG-Rg3 improved PDT in inhibiting malignant progression and stemness of osteosarcoma cell. Our finding provides a promising and practical therapeutic strategy for the combined treatment of osteosarcoma.

Limited laminectomy and foraminal decompression combined with internal fixation for treating multi-segment cervical spondylotic myelopathy: Does it effectively improve neurological function and prevent C5 palsy?

Laminectomy is an effective surgical treatment for multi-segment cervical spondylotic myelopathy (M-CSM) but usually results in C5 palsy. Some surgical techniques to restore the spinal sequence, increase the intervertebral foramen diameter, and limit the spinal cord drift distance have been proposed; however, it is unclear whether these procedures can avoid this complication.To investigate the clinical efficacy of limited laminectomy and foraminal decompression with fixation (LLFDF) for improving neurological recovery and preventing C5 palsy.A total of 71 patients with M-CSM were retrospectively analyzed. Thirty-nine of them were treated with LLFDF (group A) and 32 with normal laminectomy with fixation (NLF; group B) after 3 months of formal conservative treatment. Pre- and postoperative neurological function, spinal cord drift distance, cervical curvature index (CCI), and number of C5 palsy cases were recorded and analyzed.There was no significant intergroup difference in the surgical time or intraoperative blood loss (P >.05). The laminectomy widths in groups A and B were 16.7 ±â€Š2.6 mm and 21.8 ±â€Š2.9 mm, respectively (P <.01), while the spinal cord drift distances were 2.3 ±â€Š0.4 mm and 3.6 ±â€Š0.7 mm, respectively (P <.01). The mean Japanese Orthopedic Association score of both groups increased significantly after surgery (P <.01), and no significant difference was noted at any observation time points (P >.05). Both groups demonstrated significant CCI improvements after surgery compared with those before surgery (P <.01). There were 2 cases of C5 palsy in group A (5.1%) and 8 cases in group B (25.0%), and the difference was significant (P <.05).LLFDF can relieve spinal compression and considerably promote neurological recovery. Moreover, it restricts excessive spinal cord back drifting and decreases the incidence of C5 palsy.

Differentiation of adipose-derived stem cells into Schwann cell-like cells through intermittent induction: potential advantage of cellular transient memory function.

BACKGROUND: Peripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Tissue engineering technology is a novel therapeutic strategy, and mesenchymal stromal cells (MSCs) are promising seed cells for nerve tissue engineering. However, the efficiency of traditional methods for inducing the differentiation of MSCs to Schwann cell-like cells (SCLCs) remains unsatisfactory. METHODS: Here, we propose an intermittent induction method with alternate use of complete and incomplete induction medium to induce differentiation of adipose-derived stem cells (ASCs) to SCLCs. The time dependence of traditional induction methods and the efficiency of the intermittent induction method and traditional induction methods were evaluated and compared using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and co-culture with the dorsal root ganglion (DRG) in vitro. Cell transplantation was used to compare the effects of the traditional induction method and the intermittent induction method in repairing sciatic nerve defects in vivo. RESULTS: The results of the present study indicated that the intermittent induction method is more efficient than traditional methods for inducing ASCs to differentiate into SCLCs. In addition, SCLCs induced by this method were closer to mature myelinating Schwann cells and were capable of secreting neurotrophins and promoting DRG axon regeneration in vitro. Furthermore, SCLCs induced by the intermittent induction method could repair sciatic nerve defects in rats by cell transplantation in vivo more effectively than those produced by traditional methods. CONCLUSION: Intermittent induction represents a novel strategy for obtaining seed cells for use in nerve tissue engineering.

Reasons and risk factors for irregular-interval endoscopic variceal sclerotherapy in patients with esophageal variceal bleeding.

OBJECTIVE: Endoscopic variceal sclerotherapy (EVS) is usually carried out at weekly intervals in patients with esophageal variceal bleeding (EVB). However, some patients receive sclerotherapy at irregular intervals. In this study we aimed to elucidate the reasons and risk factors for irregular-interval sclerotherapy in patients with EVB, and to evaluate the safety and efficacy of interrupted irregular intervals in these patients. METHODS: Medical records of patients who were admitted to the Chinese PLA General Hospital from December 2013 to June 2015 for EVS were retrospectively analyzed. EVS sessions were scheduled to be repeated at regular weekly intervals. However, some of these patients received at least one treatment session at irregular intervals (mainly <7 days). This irregular-interval group was further divided into those whose treatment was rescheduled for emergency and elective reasons. RESULTS: Irregular treatment intervals were mainly caused by early rebleeding, initial emergency treatment, and holidays. However, there were no differences in the rates of complication and variceal eradication between patients treated at weekly and irregular intervals. Multivariate logistic regression analysis identified ascites (P = 0.0009), variceal erosion (P = 0.0003), and maximum injected volume of sclerosing agent per session (P = 0.0008) to be associated with emergency irregular-interval treatment. Only age differed between the elective irregular-treatment and weekly treatment groups. CONCLUSIONS: Early rebleeding, initial emergency treatment, and treatment over holidays may necessitate irregular sclerotherapy intervals in patients with EVB. Moreover, ascites, variceal erosion, and maximum injected volume of sclerosing agent per session are risk factors for emergency sclerotherapy, whereas elective adjustments to treatment schedules as a result of holidays do not affect the outcomes of patients undergoing EVS for EVB.

Extracellular matrix from human umbilical cord-derived mesenchymal stem cells as a scaffold for peripheral nerve regeneration.

The extracellular matrix, which includes collagens, laminin, or fibronectin, plays an important role in peripheral nerve regeneration. Recently, a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche. However, extensive clinical use of Schwann cells remains limited because of the limited origin, loss of an autologous nerve, and extended in vitro culture times. In the present study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs), which are easily accessible and more proliferative than Schwann cells, were used to prepare an extracellular matrix. We identified the morphology and function of hUCMSCs and investigated their effect on peripheral nerve regeneration. Compared with a non-coated dish tissue culture, the hUCMSC-derived extracellular matrix enhanced Schwann cell proliferation, upregulated gene and protein expression levels of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor in Schwann cells, and enhanced neurite outgrowth from dorsal root ganglion neurons. These findings suggest that the hUCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches.

Identification of Changes in Gene expression of rats after Sensory and Motor Nerves Injury.

Wallerian degeneration is a sequence of events in the distal stump of axotomized nerves. Despite large numbers of researches concentrating on WD, the biological mechanism still remains unclear. Hence we constructed a rat model with both motor and sensory nerves injury and then conducted a RNA-seq analysis. Here the rats were divided into the 4 following groups: normal motor nerves (NMN), injured motor nerves (IMN), normal sensory nerves (NSN) and injured sensory nerves (ISN). The transcriptomes of rats were sequenced by the Illumina HiSeq. The differentially expressed genes (DEGs) of 4 combinations including NMN vs. IMN, NSN vs. ISN, NMN vs. NSN and IMN vs. ISN were identified respectively. For the above 4 combinations, we identified 1666, 1514, 95 and 17 DEGs. We found that NMN vs. IMN shared the most common genes with NSN vs. ISN indicating common mechanisms between motor nerves injury and sensory nerves injury. At last, we performed an enrichment analysis and observed that the DEGs of NMN vs IMN and NSN vs. ISN were significantly associated with binding and activity, immune response, biosynthesis, metabolism and development. We hope our study may shed light on the molecular mechanisms of nerves degeneration and regeneration during WD.

Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.