Electrochemical activated molybdenum oxides based multiphase heterostructures with high hydrogen evolution activity in alkaline condition.

Electrochemical activation is an effective method for synthesizing economically feasible heterogeneous hydrogen evolution reaction (HER) electrocatalysts. Herein, we first synthesized MoO2-Co2Mo3O8precatalyst, which was electrochemically activated to produce K2Mo3O10within the original phase to form the heterogeneous structure. The electrochemically activated samples demonstrate exceptional HER activity in alkaline medium, which exhibit a low overpotential of 31 mV at current density of 10 mA cm-2(135 mV at 100 mA cm-2), as well as a small Tafel slope of 34 mV dec-1. This is due to the creation of multiphase heterostructures that prompt interfacial interactions and accelerate charge transfer. Simultaneously, the creation of additional active sites increases their intrinsic activities. The combined effects collectively enhance the HER performance. The application of this method in the preparation of HER catalysts is still relatively unexplored, thus rendering our work a pioneering contribution to the field.

Interface prompted highly efficient hydrogen evolution of MoS2/CoS2 heterostructures in a wide pH range.

Interfacial electronic characteristics are crucial for the hydrogen evolution reaction (HER), especially in nanoscale heterogeneous catalysts. In this work, we found that the synergistic activation of CoS2 and MoS2 (2H-MoS2 and 1T-MoS2) greatly enhances the HER activity in a wide pH range compared to those of each component. The Gibbs free energies for hydrogen adsorption at interfacial Co sites are as low as -0.08 (-0.25) eV and -0.20 (0.01) eV for 2H-MoS2/CoS2 and 1T-MoS2/CoS2 heterostructures in acidic (alkaline) media, respectively, which are even superior to that of Pt(111) (-0.09 eV). Moreover, the theoretical exchange current density of MoS2/CoS2 can reach ∼1.98 × 10-18 A site-1 (∼8.43 A mg-1). Experimentally, MoS2/CoS2 exhibits a greatly reduced overpotential of 54 (46) mV and a Tafel slope of 42 (50) mV dec-1 under acidic (alkaline) conditions. The improved performance mainly originates from the synergistically activated interfacial Co atoms with better electron localization and local bonding. The interfacial effect enhances the electron conductivity and improves the H adsorption characteristics, making MoS2/CoS2 highly valuable as efficient HER electrocatalysts.

Mechanical and chemical cues synergistically promote human venous smooth muscle cell osteogenesis through integrin ß1-ERK1/2 signaling: A cell model of hemodialysis fistula calcification.

Arteriovenous fistula (AVF) is the vascular access of choice for renal replacement therapy. However, AVF is susceptible to calcification with a high prevalence of 40%-65% in chronic hemodialysis patients. Repeated needle puncture for hemodialysis cannulation results in intimal denudation of AVF. We hypothesized that exposure to blood shear stress in the medial layer promotes venous smooth muscle cell (SMC) osteogenesis. While previous studies of shear stress focused on arterial-type SMCs, SMCs isolated from the vein had not been investigated. This study established a venous cell model of AVF using the fluid shear device, combined with a high phosphate medium to mimic the uremic milieu. Osteogenic gene expression of venous SMCs upon mechanical and chemical cues was analyzed in addition to the activated cell signaling pathways. Our findings indicated that upon shear stress and high phosphate environment, mechanical stimulation (shear stress) had an additive effect in up-regulation of an early osteogenic marker, Runx2. We further identified that the integrin ß1-ERK1/2 signaling pathway was responsible for the molecular basis of venous SMC osteogenesis upon shear stress exposure. Mitochondrial biogenesis also took part in the early stage of this venopathy pathogenesis, evident by the up-regulated mitochondrial transcription factor A and mitochondrial DNA polymerase γ in venous SMCs. In conclusion, synergistic effects of fluid shear stress and high phosphate induce venous SMC osteogenesis via the ERK1/2 pathway through activating the mechanosensing integrin ß1 signaling. The present study identified a promising druggable target for reducing AVF calcification, which deserves further in vivo investigations.

Nano-dendrite structured cobalt phosphide based hybrid supercapacitor with high energy storage and cycling stability.

The supercapacitors possessing high energy storage and long serving period have strategic significance to solve the energy crisis issues. Herein, fluffy nano-dendrite structured cobalt phosphide (CoP) is grown on carbon cloth through simple hydrothermal and electrodeposition treatments (CoP/C-HE). Benefit from its excellent electrical conductivity and special structure, CoP/C-HE manifests a high specific capacity of 461.4 C g-1at 1 A g-1. Meanwhile, the capacity retention remains 92.8% over 10 000 cycles at 5 A g-1, proving the superior cycling stability. The phase conversion of Co2P during the activation process also contributes to the improved performance. The assembled two-electrode asymmetric supercapacitor demonstrates excellent performance in terms of energy density (42.4 W h kg-1at a power density of 800.0 W kg-1) and cycling stability (86.3% retention over 5000 cycles at 5 A g-1), which is superior to many reported cobalt-based supercapacitors. Our work promotes the potential of transition metal phosphides for the applications in supercapacitors.

Electrochemical Molecular Switch for the Selective Profiling of Cysteine in Live Cells and Whole Blood and for the Quantification of Aminoacylase-1.

A first-of-a-kind latent electrochemical redox probe, ferrocene carbamate phenyl acrylate (FCPA), was developed for the selective detection of cysteine (Cys) and aminoacylase (ACY-1). The electrochemical signal generated by this probe was shown to be highly specific to Cys and insensitive to other amino acids and biological redox reactants. The FCPA-incorporated electrochemical sensor exhibited a broad dynamic range of 0.25-100 µM toward Cys. This probe also proficiently monitored the ACY-1-catalyzed biochemical transformation of N-acetylcysteine (NAC) into Cys, and this proficiency was used to develop an electrochemical assay for quantifying active ACY-1, which it did so in a dynamic range of 10-200 pM (0.1-2 mU/cm3) with a detection limit of 1 pM (0.01 mU/cm3). Furthermore, the probe was utilized in real-time tracking and quantification of cellular Cys production, specifically in Escherichia coli W3110, along with a whole blood assay to determine levels of Cys and spiked ACY-1 in blood with a reliable analytical performance.

Selective admission policy of medical undergraduates in western China: applicants' real attitudes to the choice of a rural medical career.

INTRODUCTION: Since 2010, the Chinese government has been introducing selective admission policy to recruit rural students for 5-year western medicine and traditional Chinese medicine undergraduate education in order to improve rural townships' medical services system in western China. This study aimed to analyse the selective admission policy in western China from the perspective of medical students' attitudes towards rural career choice. METHODS: A cross-sectional survey was conducted and an anonymous questionnaire was used to investigate a sample of medical undergraduates chosen under the selective admission policy. RESULTS: The results indicate that medical undergraduates' enthusiasm to work in rural areas was very limited in Gansu province, western China. Extrinsic motivation played a more important role in rural career choice than intrinsic motivation. The students' attitudes were affected by socioeconomic and cultural conditions, which determined their personal and professional environment. Course major and family economic conditions were associated with their self-decisions. CONCLUSION: Further educational intervention should emphasise the students' humanistic inner qualities and recognition of professional value. Further policy adjustment should considered, for example improving social policy-based regional character and national development strategies.

Hybrid Quantum-Classical Approach to Quantum Optimal Control.

A central challenge in quantum computing is to identify more computational problems for which utilization of quantum resources can offer significant speedup. Here, we propose a hybrid quantum-classical scheme to tackle the quantum optimal control problem. We show that the most computationally demanding part of gradient-based algorithms, namely, computing the fitness function and its gradient for a control input, can be accomplished by the process of evolution and measurement on a quantum simulator. By posing queries to and receiving answers from the quantum simulator, classical computing devices update the control parameters until an optimal control solution is found. To demonstrate the quantum-classical scheme in experiment, we use a seven-qubit nuclear magnetic resonance system, on which we have succeeded in optimizing state preparation without involving classical computation of the large Hilbert space evolution.

CITED2 silencing sensitizes cancer cells to cisplatin by inhibiting p53 trans-activation and chromatin relaxation on the ERCC1 DNA repair gene.

In this study, we show that silencing of CITED2 using small-hairpin RNA (shCITED2) induced DNA damage and reduction of ERCC1 gene expression in HEK293, HeLa and H1299 cells, even in the absence of cisplatin. In contrast, ectopic expression of ERCC1 significantly reduced intrinsic and induced DNA damage levels, and rescued the effects of CITED2 silencing on cell viability. The effects of CITED2 silencing on DNA repair and cell death were associated with p53 activity. Furthermore, CITED2 silencing caused severe elimination of the p300 protein and markers of relaxed chromatin (acetylated H3 and H4, i.e. H3K9Ac and H3K14Ac) in HEK293 cells. Chromatin immunoprecipitation assays further revealed that DNA damage induced binding of p53 along with H3K9Ac or H3K14Ac at the ERCC1 promoter, an effect which was almost entirely abrogated by silencing of CITED2 or p300. Moreover, lentivirus-based CITED2 silencing sensitized HeLa cell line-derived tumor xenografts to cisplatin in immune-deficient mice. These results demonstrate that CITED2/p300 can be recruited by p53 at the promoter of the repair gene ERCC1 in response to cisplatin-induced DNA damage. The CITED2/p300/p53/ERCC1 pathway is thus involved in the cell response to cisplatin and represents a potential target for cancer therapy.

[Clinical therapy of Zisheng decoction recipe for chronic atrophic gastritis with intestinal metaplasia].

To explore the therapeutic effect and security of Zisheng decoction recipein treatment of the chronic atrophic gastritis (CAG) with intestinal metaplasia(IM). A total of 147 eligible cases were randomly divided into the traditional Chinese medicine group, Western medicine group and the combined group,47 cases in each group. Zisheng decoction recipe, famotidine, as well as Zisheng decoction recipe + famotidine were respectively given in the above three groups, with a treatment course of 30 d. The symptoms of traditional Chinese medicine, pathological score of gastric mucosa and the negative rate of Helicobacter pylori before and after treatment were observed in each group.The changes in pepsinogen Ⅰ (PGⅠ), pepsinogen Ⅱ (PGⅡ), gastrin-17 (GAS-17) and endothelin-1 (ET-1)were also detected to compare the efficient and safety indexes in the three groups. The combined group was better than the traditional Chinese medicine groupand the Western medicine group in total effective rate (P<0.05), pathological score of gastric mucosa and the negative rate of Helicobacter pylori, and serum indexes improvement (P<0.05). The improvement in TCM symptom score was more obvious in traditional Chinese medicine group and combined group than the Western medicine group (P<0.05). In the comparison ofincidence of complications,heart, liver and renal dysfunction, the traditional Chinese medicine group (2 case,4.8%)< the combined group (7 case,15.2%)

A new electrochemical substrate for rapid and sensitive in vivo monitoring of ß-galactosidase gene expressions.

A 4-Methoxyphenyl-ß-galactopyranoside (4-MPGal) substrate incorporating 4-methoxy phenol (4-MP) as an electrochemical reporter is described for the monitoring of ß-Galactosidase (ß-Gal) gene expressions. ß-Gal derived from Escherichia coli (E. coli) and Aspergillus oryzae (A. oryzae) were investigated, while a graphene oxide film modified electrode was employed as the transducer. The electrochemical signal of 4-MPG within 4-MPGal was masked by protecting their hydroxyl group with galactose. The externally added ß-Gal triggered the deprotection through specific enzymatic hydrolysis with concomitant release of 4-MP. The apparent Km and Vmax values of 4-MPGal are determined to be 0.21 mM and 0.51 µM min(-1) mg of ß-Gal(-1) (E. coli), which is consistent with the previous reports. To detect ß-Gal derived from E. coli, cyclic voltammetry (CV) provides linear ranges of 12-1200 ng mL(-1) and 1.2-12 µg mL(-1) with a limit of detection (LOD) of 5 ng mL(-1), while differential pulse voltammetry (DPV) shows a linear range of 1.2-120 ng mL(-1) and LOD of 1 ng mL(-1). To detect ß-Gal derived from A. oryzae, CV provides linear ranges of 0.1-100 ng mL(-1) and 0.1-1 µg mL(-1) with a LOD of 0.06 ng mL(-1), while DPV shows a linear range of 10 pg mL(-1)-10 ng mL(-1) with a LOD of 8 pg mL(-1). Moreover, we set up a platform for the real-time in vivo monitoring of ß-Gal gene expressions in E. coli cultivated through microbiological culture. The developed sensing platform using 4-MPGal as a substrate is simple, rapid, sensitive, specific and advantageous over its laborious optical analogues.

EBV-encoded LMP-1 sensitizes nasopharyngeal carcinoma cells to genotoxic drugs by down-regulating Cabin1 expression.

The oncogenic latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is involved in the pathogenesis of human nasopharyngeal carcinoma (NPC) and lymphoma. We and other authors have shown earlier that LMP1 induces apoptosis and inhibits xenograft tumor growth in mice, but the mechanism underlying these processes has not been investigated so far. In the present study, we show that knockdown of LMP1 renders the EBV-positive NPC cell line CG-1 resistant to various genotoxic drugs (cisplatin, etoposide, and adriamycin). LMP1 inhibits the expression of Cabin1, a Ca(2+) regulated protein shown earlier to inhibit calcineurin. Knockdown of calcineurin binding protein (Cabin1) with small hairpin RNA sensitizes CG-1 cells to genotoxic drugs. In contrast, LMP1 overexpression reduces Cabin1 level and renders both CG-1 cells and EBV-negative NPC cell lines sensitive to cisplatin. The c-Jun-N-terminal kinase (JNK) and ERK pathways are required for LMP1-induced suppression of Cabin1 at the transcriptional level. Chromatin immunoprecipitation assays further confirm that the JNK-activated transcription factor AP-1 mediates the LMP1-induced down-regulation of Cabin1 gene expression. LMP1 knockdown also increases the resistance of xenograph tumors to cisplatin in mice, therefore confirming the relevance of our findings in vivo. This study reveals the molecular mechanism underlying the pro-apoptotic activity of LMP1 during cisplatin-based NPC chemotherapy.

Aerophobic P-MoS2 on MOF-Derived Co,N-Codoped Carbon Nanosheets with Accelerated H2 Bubble Release Dynamics for Efficient Alkaline Water Splitting at 1000 mA cm-2.

Rapid bubble release at high current densities results in the detachment of catalysts and performance degradation, posing a persistent challenge in actual alkaline water electrolysis (AWE). Here, hierarchical nanosheet structures (CoNC@P-MoS2) are constructed, with P-doped MoS2 on the surface of Co,N-codoped carbon. It exhibits low hydrogen evolution reaction overpotentials of 30 and 354 mV at 10 and 1000 mA cm-2 in 1 M KOH, respectively, with a small Tafel slope of 36 mV dec-1. The constructed CoNC@P-MoS2||NiFe-DLH cell requires only 1.44 and 1.92 V to achieve overall water splitting at 10 and 1000 mA cm-2, which outperforms the traditional catalysts like Pt/C||IrO2. The introduction of P stabilizes surface hydroxyl (OH*) and increases the proton penetration depth, thereby greatly enhancing its intrinsic activity. It also makes the surface aerophobic by introducing more microfeatures, which greatly improves the geometric activity by increasing the bubble release rate (∼5.8 times). Low energy consumption of 3.92 kW h Nm-3 was achieved with an energy efficiency close to 80%. Bubble growth kinetics analysis reveals that the time and growth factors for CoNC@P-MoS2 are increased to 0.54 and 11.79 from 0.45 and 6.09 for CoNC, respectively, which highlights its fast bubble reaction dynamics. The results suggest the feasibility of CoNC@P-MoS2 as a potential high-performance catalyst in commercial AWE.

Electrocatalytic Reduction of Carbon Dioxide in Acidic Electrolyte with Superior Performance of a Metal-Covalent Organic Framework over Metal-Organic Framework.

CO2 electroreduction (CO2RR) to generate valuable chemicals in acidic electrolytes can improve the carbon utilization rate in comparison to that under alkaline conditions. However, the thermodynamically more favorable hydrogen evolution reaction under an acidic electrolyte makes the CO2RR a big challenge. Herein, robust metal phthalocyanine(Pc)-based (M = Ni, Co) conductive metal-covalent organic frameworks (MCOFs) connected by strong metal tetraaza[14]annulene (TAA) linkage, named NiPc-NiTAA and NiPc-CoTAA, are designed and synthesized to apply in the CO2RR in acidic electrolytes for the first time. The optimal NiPc-NiTAA exhibited an excellent Faradaic efficiency (FECO) of 95.1% and a CO partial current density of 143.0 mA cm-2 at -1.5 V versus the reversible hydrogen electrode in an acidic electrolyte, which is 3.1 times that of the corresponding metal-organic framework NiPc-NiN4. The comparison tests and theoretical calculations reveal that in-plane full π-d conjugation MCOF with a good conductivity of 3.01 × 10-4 S m-1 accelerates migration of the electrons. The NiTAA linkage can tune the electron distribution in the d orbit of metal centers, making the d-band center close to the Fermi level and then activating CO2. Thus, the active sites of NiPc and NiTAA collaborate to reduce the *COOH formation energy barrier, favoring CO production in an acid electrolyte. It is a helpful route for designing outstanding conductive MCOF materials to enhance CO2 electrocatalysis under an acidic electrolyte.

Establishment of national standards of SARS-CoV-2 variants in Taiwan.

Objectives: In response to the pandemic, the Taiwan Food and Drug Administration (TFDA) established an initial SARS-CoV-2 RNA national standard based on the original Wuhan strain. However, with the depletion of the first national standard and continued mutation of the virus, the establishment of new national standards was imminent. Methods: Hence, new candidate national standards were established by heat-inactivation for 30 min for six representative strains of SARS-CoV-2, comprising the original strain and five variants with anticipated concentrations of 7.70 Log10 international units (IU)/mL each. To enhance the credibility of these national standards, the TFDA extended invitations to both domestic and international institutions to participate in a collaborative study. A total of eight participants contributed eleven datasets, incorporating two methods and targeting four distinct genes. Results: Based on these collective findings, the quantified viral RNA concentrations for each SARS-CoV-2 national standard strain are 7.69, 7.70, 7.69, 7.44, 7.52, and 7.29 Log10 IU/mL with Wuhan, alpha, beta, gamma, delta, and omicron strain, respectively. Conclusions: These newly established national standards will continue to be made available to the industry, serving as a fundamental reference for the development and quality control of nucleic acid in vitro diagnostic (IVD) reagents in Taiwan.

Multiple-Strategy Design of MOF-Derived N, P Co-Doped MoS2 Electrocatalysts Toward Efficient Alkaline Hydrogen Evolution and Overall Water Splitting.

The multiple strategy design is crucial for enhancing the efficiency of nonprecious electrocatalysts in hydrogen evolution reaction (HER). In this work, we successfully synthesized N, P-codoped MoS2 nanosheets as highly efficient catalysts by integrating doping effects and phase engineering using a porous metal-organic framework (MOF) template. The electrocatalysts exhibit excellent bifunctional activity and stability in alkaline media. The N, P codoping induces electron redistribution to enhance conductivity and promote the intrinsic activity of the electrocatalysts. It optimizes the H* adsorption free energy and the dissociative adsorption energy, resulting in significant enhancement of HER activity. Moreover, the porous MOF structure exposes a large number of electrochemically active sites and facilitates the diffusion of ions and gases, which improve charge transfer efficiency and structural stability. Specifically, at a current density of 10 mA cm-2, the overpotential of the HER is only 32 mV, with a Tafel slope of 47 mV dec-1 and Faradaic efficiency as high as 98.51% (at 100 mA cm-2). Only a 338 mV overpotential is required to achieve a current density of 50 mA cm-2 for oxygen evolution reaction (OER), and a potential of 1.49 V (at 10 mA cm-2) is sufficient to drive overall water splitting. Further experimental measurements and first-principles calculations evidence that the exceptional performance is primarily attributed to the dual functionality of N and P dopants, which not only activate additional S sites but also initialize the phase transition of 2H to 1T-MoS2 to facilitate the rapid charge transfer. Through in-depth exploration of the combined design of multiple strategies for efficient catalysts, our work paves a new way for the development of future efficient nonprecious metal catalysts.

Particulate Cell Wall Materials of Lactobacillus acidophilus as Vaccine Adjuvant.

We evaluated Lactobacillus acidophilus (LA) for adjuvant application in animal vaccines. LA particles (LAPs) are made by treating LA with purification processes and high-pressure homogenization (HPH). We found that LAPs treated with HPH with trehalose and emulsifiers had an average particle size of 179 nm, considerably smaller than LAPs without additives. First, we evaluated the adjuvanticity of LAPs using a murine model with ovalbumin antigens, revealing that LAPs, especially in a five-fold concentration, could induce a considerable antibody response compared with other current adjuvants. In poultry vaccination tests using inactivated Newcastle disease virus, LAPs alone could induce a similar antibody response compared to commercial water-in-oil (W/O) adjuvant ISA70, a commercial adjuvant, at weeks 4 and 6; however, they declined faster than ISA70 at weeks 8 and 10. LAPs added to conventional adjuvant materials, such as mineral oil-based O/W emulsions, showed similar adjuvanticity to ISA70. LA-H5-C, composed of carbomer, emulsifiers and trehalose showed no significant body weight change in acute toxicity compared to other adjuvants including ISA70, making formulated LAPs a potential candidate for use as a veterinary vaccine adjuvant.

A Soil-Isolated Streptomyces spororaveus Species Produces a High-Molecular-Weight Antibiotic AF1 against Fungi and Gram-Positive Bacteria.

The overuse of antibiotics has resulted in the emergence of antibiotic resistance, not only in bacteria but also in fungi. Streptomyces are known to produce numerous secondary metabolites including clinically useful antibiotics. In this study, we screened for antibiotic-producing actinobacteria from soils in Taipei and discovered a Streptomyces strain SC26 that displayed antimicrobial activities against Gram-positive bacteria and fungi, but the compounds are heat-labile. Upon UV mutagenesis, a late-sporulation mutant SC263 was isolated with the same antibiotic spectrum but increased in thermostability. The nature of the antibiotic is not clear, but its activity was resistant to proteolytic, nucleolytic and pancreatic digestions, and was retained by the 100 kDa membrane during filtration. To gather more information on SC263, the genome was sequenced, which produced three contigs with a total of 8.2 Mb and was assigned to the species of Streptomyces spororaveus based on the average nucleotide identity to the reference species S. spororaveus NBRC 15456.

Functioning tailor-made 3D-printed vascular graft for hemodialysis.

BACKGROUND: The two ends of arteriovenous graft (AVG) are anastomosed to the upper limb vessels by surgery for hemodialysis therapy. However, the size of upper limb vessels varies to a large extent among different individuals. METHODS: According to the shape and size of neck vessels quantified from the preoperative computed tomography angiographic scan, the ethylene-vinyl acetate (EVA)-based AVG was produced in H-shape by the three-dimensional (3D) printer and then sterilized. This study investigated the function of this novel 3D-printed AVG in vitro and in vivo. RESULTS: This 3D-printed AVG can be implanted in the rabbit's common carotid artery and common jugular vein with ease and functions in vivo. The surgical procedure was quick, and no suture was required. The blood loss was minimal, and no hematoma was noted at least 1 week after the surgery. The blood flow velocity within the implanted AVG was 14.9 ± 3.7 cm/s. Additionally, the in vitro characterization experiments demonstrated that this EVA-based biomaterial is biocompatible and possesses a superior recovery property than ePTFE after hemodialysis needle cannulation. CONCLUSIONS: Through the 3D printing technology, the EVA-based AVG can be tailor-made to fit the specific vessel size. This kind of 3D-printed AVG is functioning in vivo, and our results realize personalized vascular implants. Further large-animal studies are warranted to examine the long-term patency.

Evaluating Different Strategies on the Blood Collection Counter Settings to Improve Patient Waiting Time in Outpatient Units.

Long patient waiting time is one of the major problems in the healthcare system and it would decrease patient satisfaction. Previous studies usually investigated how to improve the treatment flow in order to reduce patient waiting time or length of stay. The studies on blood collection counters have received less attention. Therefore, the objective of this study is to reduce the patient waiting time at outpatient clinics for metabolism and nephrology outpatients. A discrete-event simulation is used to analyze the four different strategies for blood collection counter resource allocation. Through analyzing four different strategic settings, the experimental results revealed that the maximum number of patients waiting before the outpatient clinics was reduced from 41 to 33 (20%); the maximum patient waiti-ng time at the outpatient clinics was decreased from 201.6 minutes to 83 minutes (59%). In this study, we found that adjusting the settings of blood collection counters would be beneficial. Assigning one exclusive blood collection counter from 8 to 10 am is the most suitable option with the least impact on the operational process for hospital staff. The results provide managerial insight regarding the cost-effective strategy selection for the hospital operational strategy.

Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6.

BACKGROUND: Life-long peritoneal dialysis (PD) as a renal replacement therapy is limited by peritoneal fibrosis. Previous studies showed immunomodulatory and antifibrotic effects of adipose-derived mesenchymal stem cells (ADSCs) on peritoneal fibrosis. However, the role of the peritoneal macrophage in this process remains uninvestigated. METHODS: We examined the therapeutic effects of ADSC and bone marrow-derived mesenchymal stem cells (BM-MSC) in the rat model of dialysis-induced peritoneal fibrosis using methylglyoxal. In addition, treatment of macrophages with the conditioned medium of ADSC and BM-MSC was performed individually to identify the beneficial component of the stem cell secretome. RESULTS: In the in vivo experiments, we found dialysis-induced rat peritoneal fibrosis was attenuated by both ADSC and BM-MSC. Interestingly, ADSC possessed a more prominent therapeutic effect than BM-MSC in ameliorating peritoneal membrane thickening while also upregulating epithelial cell markers in rat peritoneal tissues. The therapeutic effects of ADSC were positively associated with M2 macrophage polarization. In the in vitro experiments, we confirmed that interleukin-6 (IL-6) secreted by MSCs upon transforming growth factor-ß1 stimulation promotes M2 macrophage polarization. CONCLUSIONS: In dialysis-induced peritoneal fibrosis, MSCs are situated in an inflammatory environment of TGF-ß1 and secrete IL-6 to polarize macrophages into the M2 phenotype. Our findings reveal a previously unidentified role of tissue macrophage in this antifibrotic process. ADSC has the advantage of abundance and accessibility, making the application values extremely promising. In dialysis-induced peritoneal fibrosis, peritoneal mesothelial cells secrete transforming growth factor-ß1 (TGF-ß1) when exposed to methylglyoxal (MGO)-containing peritoneal dialysate. When situated in TGF-ß1, the inflammatory environment induces mesenchymal stem cells to secrete interleukin-6 (IL-6), IL-6 polarizes macrophages into the M2 phenotype. The dominant peritoneal tissue M2 macrophages, marked by upregulated Arg-1 expression, account for the attenuation of MGO-induced dedifferentiation of peritoneal mesothelial cells to maintain epithelial integrity.