Impacts of O2:CH4 ratios and CH4 concentrations on the denitrification and CH4 oxidations of a novel AME-AD system.

Aerobic methane (CH4) oxidation coupled to denitrification (AME-D) is a promising process for the denitrification of low C/N wastewater. Compared with anaerobic denitrifying bacteria, aerobic denitrifying bacteria may enable AME-D have high denitrification ability under aerobic conditions. This study constructed a novel aerobic methane oxidation coupled to aerobic denitrification (AME-AD) system using the typical aerobic denitrifying bacteria Paracoccus pantotrophus ATCC35512 and the typical aerobic methane oxidizing bacteria Methylosinus trichosporium OB3b. The denitrification and CH4 oxidations of AME-AD with different O2:CH4 ratios (0:1, 0.25:1, 0.5:1, 0.75:1, 1:1 and 1.25:1) and CH4 concentrations (0, 14000, 28000, 42000, 56000 and 70000 mg m-3) were investigated in batch experiments. Higher O2:CH4 ratios can significantly improve the denitrification and CH4 oxidations of the AME-AD (P < 0.05). The treatment with an O2:CH4 ratio of 1.25:1 had the highest denitrification rate (0.036 mg h-1) and highest CH4 oxidation rate (0.20 mg h-1). The CH4 concentration in the headspace was positively correlated with the AME-AD denitrification rate. The calculated CH4/NO3-(mol/mol) in most treatments ranged from 5.76 to 6.84. In addition, excessively high O2 and CH4 concentrations can lead to increased nitrous oxide (N2O) production in AME-AD. The N2O production rate was up to 1.00 µg h-1 when the O2:CH4 was 1.25:1. These results can provide data support for the application of AME-AD for low-C/N wastewater treatment and greenhouse gas emission reduction.

Steroidal saponins PPI/CCRIS/PSV induce cell death in pancreatic cancer cell through GSDME-dependent pyroptosis.

Pancreatic cancer is highly aggressive and lethal, and treatment options for it are limited. Gasdermin E (GSDME) is highly expressed in pancreatic cancer and can induce pyroptosis. In this type of programmed cell death, cells swell and emit large gas bubbles through their plasma membranes. Hence, GSDME induction is potentially an efficacious therapeutic approach against pancreatic cancer. In the present study, we found that the steroidal saponins polyphyllin I (PPI), collettiside III (CCRIS), and paris saponin V (PSV) significantly inhibited PANC-1, AsPC-1, and BxPC-3 cell proliferation. PPI/CCRIS/PSV altered the morphology of PANC-1 cells and induced the release of lactate dehydrogenase (LDH) from them. Therefore, these three constituents caused PANC-1 cells to undergo pyroptosis. This conclusion was confirmed by propidium iodide (PI) staining and flow cytometry assays. The present work also revealed that PPI/CCRIS/PSV induced pyroptosis via GSDME rather than gasdermin D (GSDMD). Whereas PPI/CCRIS/PSV induced caspase-3 to cleave GSDME, it had no such effect on GSDMD. We also established a PANC-1 xenograft tumor model in BALB/c nude mice and administered CCRIS to them as this compound demonstrated the most substantial pyroptotic effect in the in vitro experiments. This treatment significantly inhibited tumor growth in the mice by activating GSDME-dependent pyroptosis. This research demonstrates demonstrate that pyroptosis induction by PPI/CCRIS/PSV has important implications in basic science and clinical medicine. Future investigations should endeavor to determine the benefits and risks associated with the administration of these steroidal saponins as anti-PDAC therapy.

Inhibitory mechanism of KIF3A gene on nasopharyngeal carcinoma stem cells.

To investigate the inhibitory mechanism of the KIF3A gene on nasopharyngeal carcinoma (NPC) tumor stem cells. Set up a blank control group (BCG), NPC group, and KIF3A silence (si-KIF3A) group. The BCG cells were nasopharyngeal normal epithelial cell line NP69, without any treatment, and were cultured routinely; The NPC group cells are human NPC cell line CNE2 cells, which are not subjected to any treatment and are cultured routinely; si-KIF3A group cells were cultured in the offspring of human NPC cell line CNE2 infected with Lentivirus knockdown KIF3A gene. CCK8 was used to detect the cell proliferation ability, Western blot and qPCR were used to detect protein and related mRNA expression, while cell migration and invasion were detected using Transwell. The KIF3A protein and mRNA in the NPC group were higher than those in the BCG (P<0.05), while those in the si-KIF3A group cells were lower compared to BCG cells (P<0.05). The cell proliferation, migration and invasion activity in the si-KIF3A group were reduced than those in BCG (P<0.05). Si-KIF3A group cells HIF-1, NF-κB was reduced than that of BCG (P<0.05). The expression level of HIF-1, NF-κB protein in si-KIF3A group cells was reduced compared to BCG cells (P<0.05). Knocking down the KIF3A gene can reduce the vitality of NPC stem cells, and inhibit the malignant phenotype of NPC stem cells, via inhibiting HIF-1 and NF-κB expression.

An Anti-Noise Convolutional Neural Network for Bearing Fault Diagnosis Based on Multi-Channel Data.

In real world industrial applications, the working environment of a bearing varies with time, and some unexpected vibration noises from other equipment are inevitable. In order to improve the anti-noise performance of neural networks, a new prediction model and a multi-channel sample generation method are proposed to address the above problem. First, we proposed a multi-channel sample representation method based on the envelope time-frequency spectrum of a different channel and subsequent three-dimensional filtering to extract the fault features of samples. Second, we proposed a multi-channel data fusion neural network (MCFNN) for bearing fault discrimination, where the dropout technique is used in the training process based on a dataset with a wide rotation speed and various loads. In a noise-free environment, our experimental results demonstrated that the proposed method can reach a higher fault classification of 99.00%. In a noisy environment, the experimental results show that for the signal-to-noise ratio (SNR) of 0 dB, the fault classification averaged 11.80% higher than other methods and 32.89% higher under a SNR of -4 dB.

Narrow Pore Crossing of Active Particles under Stochastic Resetting.

We propose a two-dimensional model of biochemical activation process, whereby self-propelling particles of finite correlation times are injected at the center of a circular cavity with constant rate equal to the inverse of their lifetime; activation is triggered when one such particle hits a receptor on the cavity boundary, modeled as a narrow pore. We numerically investigated this process by computing the particle mean-first exit times through the cavity pore as a function of the correlation and injection time constants. Due to the breach of the circular symmetry associated with the positioning of the receptor, the exit times may depend on the orientation of the self-propelling velocity at injection. Stochastic resetting appears to favor activation for large particle correlation times, where most of the underlying diffusion process occurs at the cavity boundary.

7-aminocephalosporanic acid, a novel HSP90ß inhibitor, attenuates HFD-induced hepatic steatosis.

Hepatic steatosis is one of the most important causes of liver disease worldwide. Heat shock protein 90 (HSP90) is essential for numerous client proteins. Recently, more attention was focused on increased HSP90 levels in hepatic steatosis, especially HSP90ß. Thus, great efforts have been made to develop HSP90ß inhibitors, and most natural inhibitors are derived from microorganisms. In this study, using microarray chips and surface pasmon resonance (SPR) technology, we screened 189 antibiotics in order to obtain an inhibitor directly binding to the non-N-terminal domain of HSP90ß. Finally, we discovered an antibiotic, 7-aminocephalosporanic acid (7ACA), with a KD value of 6.201 µM between 7ACA and non-N-terminal domain of HSP90ß. Besides, 7ACA was predicted to interact with the middle domain (MD) of HSP90ß. In HepG2 cells, we found that 7ACA reduced cellular total cholesterol (TC) and triglyceride (TG) by decreasing sterol regulatory element-binding proteins (SREBPs). In HFD fed mice, administration of 7ACA (5, 10, and 25 mg kg-1 d-1, ig, for 12 weeks) dose-dependently decreased serum TC and TG and played an important role in protecting liver and adipose tissue from lipid accumulation. In conclusion, our study demonstrated that antibiotic 7ACA, as an HSP90ß middle domain inhibitor, was promising for the development of lipid-lowering drugs.

Research of a Thermodynamic Function (∂p∂x)T, x→0: Temperature Dependence and Relation to Properties at Infinite Dilution

In this work, we propose the idea of considering (∂p∂x)T, x→0 as an infinite dilution thermodynamic function. Our research shows that (∂p∂x)T,x→0 as a thermodynamic function is closely related to temperature, with the relation being simply expressed as: ln(∂p∂x)T, x→0=AT+B. Then, we use this equation to correlate the isothermal vapor−liquid equilibrium (VLE) data for 40 systems. The result shows that the total average relative deviation is 0.15%, and the total average absolute deviation is 3.12%. It indicates that the model correlates well with the experimental data. Moreover, we start from the total pressure expression, and use the Gibbs−Duhem equation to re-derive the relationship between (∂p∂x)T,x→0 and the infinite dilution activity coefficient (γ∞) at low pressure. Based on the definition of partial molar volume, an equation for (∂p∂x)T,x→0 and gas solubility at high pressure is proposed in our work. Then, we use this equation to correlate the literature data on the solubility of nitrogen, hydrogen, methane, and carbon dioxide in water. These systems are reported at temperatures ranging from 273.15 K to 398.15 K and pressures up to 101.325 MPa. The total average relative deviation of the predicted values with respect to the experimental data is 0.08%, and the total average absolute deviation is 2.68%. Compared with the Krichevsky−Kasarnovsky equation, the developed model provides more reliable results.

Separation efficiency of different solid-liquid separation technologies for slurry and gas emissions of liquid and solid fractions: A meta-analysis.

Solid-liquid separation (SLS) technology is widely used in the slurry management in animal farms. This study conducted a comprehensive meta-analysis of 45 published articles to evaluate the differences in separation efficiencies (SEX-SF) of various SLSs and the changes of gas emissions before and after the separation during on-farm slurry storage. The results indicated that the SEX-SF of the untreated raw slurry and acidified slurry were consistently greater than those of the digested slurry, and centrifugation resulted in greater SEX-SF than the other mechanical methods. Both measured and simulated data showed that the centrifuge technology had greater reductions in greenhouse gas (GHG) emissions relative to the screw press (56.1-58.0% vs. 38.9-40.2% for untreated slurry, and 29.7-30.2% vs. 22.5-23.2% for digested slurry), mainly due to CH4 reduction. Additionally, we identify the need for further assessment of the environmental risks that are associated with SLSs for the development of an optimal slurry management chain.

Impacts of slurry application methods and inhibitors on gaseous emissions and N2O pathways in meadow-cinnamon soil.

This study aimed to evaluate the impact of mitigation practices (slurry application methods and inhibitors applications) on gas emissions and identify the soil N2O production pathways in cattle slurry applied soil using isotopocule mapping approach. First, we compared the NH3 and N2O emissions of cattle slurry applied soil in a summer maize field experiment in north China plain (NCP) with four treatments: control (CK, no fertilization), slurry application using surface (SA-S), slurry application using band application (BA-S), and chemical fertilizer application using band application (BA-C). Then, an incubation experiment was conducted to investigate the mitigation effect of nitrification inhibitors (dicyandiamide, DCD) and denitrification inhibitors (procyanidins, PC) and their combination (DCD + PC) on gaseous N emissions with slurry applied using incorporation (IA) or surface application (SA) methods. The results showed that the total gaseous N emissions (N2O-N and NH3-N) in field were in the order of SA-S (1534 mg m-2) > BA-S (338 mg m-2) > BA-C (128 mg m-2) > CK (55 mg m-2), and the dominant N loss contributor varied from NH3 in SA-S (∼89%) to N2O in BA-S (∼94%) and BA-C (∼88%). Moreover, the isotopocule mapping approach indicated that emitted N2O of the slurry applied soil in field appeared to have lower rN2O values and led to more N2O + N2 emissions at the initial fertilization period. The incubation experiment indicated that the N2O emissions of slurry-applied soil were significantly reduced by DCD (∼45%) and DCD + PC (∼67%) application in comparison with CK (p < 0.05), and the stronger contributions of bacterial denitrification/nitrifier denitrification to N2O production were revealed by the lower δ15NSP in N2O using the isotopocule mapping approach. In conclusion, in NCP the gaseous losses of the slurry applied field can be largely reduced by using incorporation method, and greater reduction could be achieved given the simultaneous application of nitrification/denitrification inhibitors.

Administration of isoliquiritigenin prevents nonalcoholic fatty liver disease through a novel IQGAP2-CREB-SIRT1 axis.

Isoliquiritigenin (ISO) is a flavonoid extracted from the root of licorice, which serves various biological and pharmacological functions including antiinflammatory, antioxidation, liver protection, and heart protection. However, the mechanism of its action remains elusive and the direct target proteins of ISO have not been identified so far. Through cell-based screening, we identified ISO as a potent lipid-lowering compound. ISO treatment successfully ameliorated fatty acid-induced cellular lipid accumulation and improved nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by increasing PPARα-dependent lipid oxidation and decreasing SREBPs-dependent lipid synthesis. Both these signaling required the activation of SIRT1. Knockdown of SIRT1 resulted in the reversal of ISO beneficiary effects suggesting that the lipid-lowering activity of ISO was regulated by SIRT1 expression. To identify the direct target of ISO, limited proteolysis combined with mass spectrometry (LiP-SMap) strategy was applied and IQGAP2 was identified as the direct target for ISO in regulating lipid homeostasis. In the presence of ISO, both mRNA and protein levels of SIRT1 were increased; however, this effect was abolished by blocking IQGAP2 expression using siRNA. To explore how IQGAP2 regulated the expression level of SIRT1, proteome profiler human phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that ISO affected. We found that through phosphorylation of CREB, ISO transduced signals from IQGAP2 to upregulate SIRT1 expression. Thus, we not only demonstrated the molecular basis of ISO in regulating lipid metabolism but also exhibited for the first time a novel IQGAP2-CREB-SIRT1 axis in treating NAFLD/NASH.

A new technique for treating hiatal hernia with gastroesophageal reflux disease: the laparoscopic total left-side surgical approach.

INTRODUCTION: Although the traditional bilateral surgical approach to treat hiatal hernia (HH) with gastroesophageal reflux disease (GERD) can provide local protection of the vagus nerve, the integrity of the entire vagus nerve cannot be evaluated. Therefore, we developed and described the total left-side surgical approach (TLSA), which theoretically reduces injury to the vagus nerve, and described the detailed surgical procedure. METHODS: Initially, we performed a cadaver study to explore the characteristics of the vagus nerve. Then, we prospectively evaluated the TLSA in 5 patients with HH and GERD between June 2020 and September 2020. Demographic characteristics, surgical parameters, perioperative outcomes, and follow-up findings were analyzed. RESULTS: The TLSA was successfully used in five patients (40-64 years old), and no major complications were noted. The median total operative time was 114 min, median blood loss was 50 mL, and median postoperative hospital stay was 3.8 days. Gastrointestinal function recovered within 4 days of surgery in all the patients. The 6-month follow-up gastroscopy examination showed well-established gastroesophageal flap valves. Compared with the baseline results, the 6-month follow-up results showed lower values for the total GerdQ score (12.4 vs. 6.2) and the total esophageal acid exposure time (3.48% vs. 0.38%). Based on the European Organization for Research and Treatment of Cancer quality of life questionnaire-stomach module 52 results, the incidence of dysphagia and flatulence decreased over time after the TLSA. CONCLUSIONS: The TLSA provides a clear and broad surgical field, less trauma, and rapid recovery; moreover, it is technically simple. Although our results suggest that the TLSA provides safety and short-term efficacy and is feasible for patients with HH and GERD, long-term results from a larger clinical trial are needed to validate these findings. Trial registration ChiCTR2000034028, registration date is June 21, 2020. The study was registered prospectively.

Metacontrol of human creativity: The neurocognitive mechanisms of convergent and divergent thinking.

Creativity is a complex construct that would benefit from a more comprehensive mechanistic approach. Two processes have been defined to be central to creative cognition: divergent and convergent thinking. These two processes are most often studied using the Alternate Uses Test (heavily relying on divergent thinking), and the Remote Associates Test (heavily relying on convergent thinking, at least with analytical solutions). Although creative acts should be regarded compound processes, most behavioral and neuroimaging studies ignore the composition of basic operations relevant for the task they investigate. In order to provide leverage for a more mechanistic, and eventually even comprehensive computational, approach to creative cognition, we compare findings from divergent and convergent thinking studies and review the similarities and differences between the two underlying types of processes, from a neurocognitive perspective with a strong focus on cortical structures. In this narrative review, we discuss a broad scope of neural correlates of divergent and convergent thinking. We provide a first step towards theoretical integration, by suggesting that creative cognition in divergent- and convergent-thinking heavy tasks is modulated by metacontrol states, where divergent thinking and insight solutions in convergent-thinking tasks seem to benefit from metacontrol biases towards flexibility, whereas convergent, analytical thinking seems to benefit from metacontrol biases towards persistence. These particular biases seem to be reflected by specific cortical brain-activation patterns, involving left frontal and right temporal/parietal networks. Our tentative framework could serve as a first proxy to guide neuroscientific creativity research into assessing more mechanistic details of human creative cognition.

High-mobility group box 1 protein antagonizes the immunosuppressive capacity and therapeutic effect of mesenchymal stem cells in acute kidney injury.

BACKGROUND: Kidney ischemia reperfusion injury (IRI) is a common cause of acute kidney injury and an unavoidable consequence of kidney transplantation and still lacks specific therapeutics. Recently, mesenchymal stem cell (MSC) has been emerging as a promising cell-based therapy for IRI in the context of transplantation. MSC negatively regulates the secretion of pro-inflammatory as well as the activation of immune cells during IRI through its unique immunosuppressive property. METHODS: We employed mice kidney IRI model and MSC cell line to monitor the IRI related checkpoints. siRNAs were utilized to knock down the potential key factors for mechanistic analysis. Statistical analysis was performed by using one-way ANOVA with Tukey's post hoc procedure by SPSS. RESULTS: The expression of high-mobility group box 1 protein (HMGB1) is increased in the acute phase as well as the recovery stage of IRI. Importantly, the HMGB1 upregulation is correlated with the injury severity. HMGB1 diminishes the MSC induced immunosuppressive capacity in the presence of pro-inflammatory cytokines in vitro. Toll like receptor 4 (TLR4)-mediated inducible nitric oxide synthase (iNOS) inhibition contributes to the negative effect of HMGB1 on MSCs. HMGB1-TLR4 signaling inhibition augments the therapeutic efficacy of MSCs in mice renal IRI model. CONCLUSIONS: These findings demonstrate that HMGB1 plays a crucial role in shaping the immunoregulatory property of MSCs within the microenvironments, providing novel insights into the crosstalk between MSCs and microenvironment components, suggesting HMGB1 signals as a promising target to improve MSC-based therapy.

Complement Inhibitor CRIg/FH Ameliorates Renal Ischemia Reperfusion Injury via Activation of PI3K/AKT Signaling.

Complement activation is involved in the pathogenesis of ischemia reperfusion injury (IRI), which is an inevitable process during kidney transplantation. Therefore, complement-targeted therapeutics hold great potential in protecting the allografts from IRI. We observed universal deposition of C3d and membrane attack complex in human renal allografts with delayed graft function or biopsy-proved rejection, which confirmed the involvement of complement in IRI. Using FB-, C3-, C4-, C5-, C5aR1-, C5aR2-, and C6-deficient mice, we found that all components, except C5aR2 deficiency, significantly alleviated renal IRI to varying degrees. These gene deficiencies reduced local (deposition of C3d and membrane attack complex) and systemic (serum levels of C3a and C5a) complement activation, attenuated pathological damage, suppressed apoptosis, and restored the levels of multiple local cytokines (e.g., reduced IL-1ß, IL-9, and IL-12p40 and increased IL-4, IL-5, IL-10, and IL-13) in various gene-deficient mice, which resulted in the eventual recovery of renal function. In addition, we demonstrated that CRIg/FH, which is a targeted complement inhibitor for the classical and primarily alternative pathways, exerted a robust renoprotective effect that was comparable to gene deficiency using similar mechanisms. Further, we revealed that PI3K/AKT activation, predominantly in glomeruli that was remarkably inhibited by IRI, played an essential role in the CRIg/FH renoprotective effect. The specific PI3K antagonist duvelisib almost completely abrogated AKT phosphorylation, thus abolishing the renoprotective role of CRIg/FH. Our findings suggested that complement activation at multiple stages induced renal IRI, and CRIg/FH and/or PI3K/AKT agonists may hold the potential in ameliorating renal IRI.

Testosterone induces renal tubular epithelial cell death through the HIF-1α/BNIP3 pathway.

BACKGROUND: The morbidity of nephrolithiasis is 2-3 times higher in males than in females, suggesting that androgen plays a key role in nephrolithiasis. The death of renal tubular epithelial cells (TECs) is an important pathophysiological process contributing to the development of nephrolithiasis. Therefore, the aim of this study is to investigate whether androgen directly induces TECs apoptosis and necrosis and its underlying mechanisms in kidney stone formation. MATERIALS AND METHODS: We compared serum testosterone level between male and female healthy volunteers and kidney stone patients. The in vivo nephrolithiasis model was established using glyoxylic acid, and calcium deposits were detected by van Kossa staining. In the in vitro study using mouse TECs (TCMK-1 cells) and human TECs (HK-2 cells), apoptosis, necrosis, and the expression of BH3-only protein Bcl-2-like 19 kDa-interacting protein 3 (BNIP3) were examined incubated with different doses of testosterone using flow cytometry. Levels of apoptosis-related proteins transfected with the BNIP3 siRNA were examined by western blotting. The mitochondrial potential (ΔΨm) was detected by JC-1 staining and flow cytometry. We monitored BNIP3 expression in the testosterone-induced TECs injury model after treatment with hypoxia inducible factor 1α (HIF-1α) and/or hypoxia inducible factor 2α (HIF-2α) inhibitors to determine the upstream protein regulating BNIP3 expression. Additionally, ChIP and luciferase assays were performed to confirm the interaction between HIF-1α and BNIP3. RESULTS: Both male and female patients have significantly higher testosterones compared with healthy volunteers. More calcium deposits in the medulla were detected in male mice compared to female and castrated male mice. Testosterone induced TECs apoptosis and necrosis and increased BNIP3 expression in a dose-dependent manner. Testosterone also increased Bax expression, decreased Bcl-2 expression and induced a loss of ΔΨm. This effect was reversed by BNIP3 knockdown. HIF-1α inhibition significantly decreased BNIP3 expression and protected TECs from testosterone-induced apoptosis and necrosis. HIF-2α inhibition, however, did not influence BNIP3 expression or TECs apoptosis or necrosis. Finally, HIF-1α interacted with the BNIP3 promoter region. CONCLUSION: Based on these results, testosterone induced renal TECs death by activating the HIF-1α/BNIP3 pathway.

Transplantation of Telocytes Attenuates Unilateral Ureter Obstruction-Induced Renal Fibrosis in Rats.

BACKGROUND/AIMS: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. METHODS: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days. The degree of renal damage and fibrosis was determined using histological assessment. The expression of collagen I, fibronectin, epithelial-mesenchymal transition markers, and Smad2/3 phosphorylation was examined by western blot analyses. Real-time PCR and enzyme-linked immunosorbent assay were performed in vivo to detect the levels of transforming growth factor (TGF)-ß1 and various growth factors. RESULTS: Telocytes attenuated renal fibrosis, as evidenced by reduced interstitial collagen accumulation, decreased expression of fibronectin and collagen I, upregulation of E-cadherin, and downregulation of α-smooth muscle actin. Furthermore, telocytes decreased serum TGF-ß1 levels, suppressed Smad2/3 phosphorylation, and increased the expression of hepatocyte growth factor (HGF) in rat kidney tissue following UUO. Blockage of HGF counteracted the protective effect of telocytes on UUO-treated kidneys. Through the detection of HGF mRNA levels in vitro, we found that telocytes had no effect on HGF expression compared with renal fibroblasts. CONCLUSION: Telocytes attenuated UUO-induced renal fibrosis in rats, likely through enhancing the expression of HGF in an indirect manner.

Myeloid-derived suppressor cells in transplantation: the dawn of cell therapy.

Myeloid-derived suppressor cells (MDSCs) are a series of innate cells that play a significant role in inhibiting T cell-related responses. This heterogeneous population of immature cells is involved in tumor immunity. Recently, the function and importance of MDSCs in transplantation have garnered the attention of scientists and have become an important focus of transplantation immunology research because MDSCs play a key role in establishing immune tolerance in transplantation. In this review, we summarize recent studies of MDSCs in different types of transplantation. We also focus on the influence of immunosuppressive drugs on MDSCs as well as future obstacles and research directions in this field.

A novel cytoprotective peptide protects mesenchymal stem cells against mitochondrial dysfunction and apoptosis induced by starvation via Nrf2/Sirt3/FoxO3a pathway.

BACKGROUND: Mesenchymal stem cell (MSC) has been widely explored in the past decade as a cell-based treatment for various diseases. However, poor survival of adaptively transferred MSCs limits their clinical therapeutic potentials, which is largely ascribed to the nutrient starvation. In this study, we determined whether a novel kidney protective peptide CHBP could protect MSCs against starvation and invested the underlying mechanisms. METHODS: MSCs were subjected to serum deprivation and CHBP of graded concentrations was administered. Cell viability and apoptosis were detected by CCK-8, Annexin V/PI assay and Hoechst staining. ROS generation, mitochondrial membrane potential indicated by JC-1 and mitochondrial mass were measured by flow cytometry. The location of cytochrome c within cells was observed under fluorescence microscopy. Expressions of Nrf2, Sirt3, and FoxO3a were analyzed by western blot. In addition, preconditioning MSCs with CHBP was applied to test the possible protection against starvation. Finally, the effect of CHBP on the differentiation and self-renewal capacity of MSCs was also examined. RESULTS: CHBP improved cell viability and suppressed apoptosis in a dose dependent manner. Starvation resulted in the mitochondrial dysfunction and treatment of CHBP could alleviate mitochondrial stress by diminishing oxidative injury of ROS, restoring mitochondrial membrane potential and maintaining mitochondrial membrane integrity. Importantly, Nrf2/Sirt3/FoxO3a pathway was activated by CHBP and Sirt3 knockdown partially abolished the protection of CHBP. Moreover, MSCs pretreated with CHBP were more resistant to starvation. Under normal condition, CHBP exerted little effects on the differential and self-renewal capacity of MSCs. CONCLUSIONS: The present study demonstrated the efficient protection of CHBP upon MSCs against starvation-induced mitochondrial dysfunction and apoptosis and indicated possible involvement of Nrf2/Sirt3/FoxO3a pathway in the protective effect.

Kimura disease.

Kimura disease is a rare, benign, chronic, immune-mediated inflammatory disorder. We report a 46-year-old man who presented with a cutaneous nodule behind his left ear. Surgical removal of the growth confirmed the histological diagnosis of KD. There was no recurrence found after 3 years follow-up.