Biorthogonal Dynamical Quantum Phase Transitions in Non-Hermitian Systems.

By utilizing biorthogonal bases, we develop a comprehensive framework for studying biorthogonal dynamical quantum phase transitions in non-Hermitian systems. With the help of the previously overlooked associated state, we define the automatically normalized biorthogonal Loschmidt echo. This approach is capable of handling arbitrary non-Hermitian systems with complex eigenvalues and naturally eliminates the negative value of Loschmidt rate obtained without the biorthogonal bases. Taking the non-Hermitian Su-Schrieffer-Heeger model as a concrete example, a 1/2 change of dynamical topological order parameter in biorthogonal bases is observed which is not shown in self-normal bases. Furthermore, we discover that the periodicity of biorthogonal dynamical quantum phase transitions depends on whether the two-level subsystem at the critical momentum oscillates or reaches a steady state.

Hyper-expression and hypomethylation of TM4SF1 are associated with lymph node metastases in papillary thyroid carcinoma patients.

Lymph node metastases (LNM) are an indicator for recurrence in papillary thyroid carcinoma (PTC) patients. However, prophylactic neck dissection (ND) cannot improve survival or recurrence rate because of increased surgical complications and occult LNM. Biomarkers are needed for the prediction of high-risk of LNM to avoid unnecessary operation and reduce the missed malignant lymph nodules. GEO database was searched for the differentially expressed genes (DEGs) between PTC patients with LNM (N1) and those without LNM (N0), transcriptional and methylation data of DEGs in THCA were examined from databases. The expression and methylation of TM4SF1 in fresh and paraffin tissues of PTC patients were examined by qRT-PCR, IHC, and MSP. TM4SF1 was the only one significantly associated with LNM. UALCAN revealed that TM4SF1 was overexpressed and hypomethylated in LNM patients. MEXPRESS presented a negative correlation between gene expression and promoter methylation of TM4SF1. DEGs were enriched in multiple pathways and the Extracellular Matrix (ECM)-receptor interaction pathway showed the greatest correlation with LNM. IHC and qRT-PCR of tissues demonstrated that the expression of TM4SF1 in the N1 group was 4.5-fold higher than that in the N0 group (p<0.05). MSP exhibited that the positive rate of aberrant promoter methylation of TM4SF1 was 8.38% in N1 and 66.7% in N0 group (p<0.05). Hyper-expression and hypomethylation of TM4SF1 are associated with lymph node metastases in PTC patients.

The Remission Rate of Type 2 Diabetes Outpatients with Premixed Insulin: The Result of a 5-Year Prospective Study.

The aim of the study was to evaluate the remission rate with short-term premixed insulin therapy in newly diagnosed type 2 diabetes outpatients and investigate predictors contributing to the remission rate. A 5-year prospective study was conducted with a total of 170 patients enrolled. Patients were treated with premixed insulin monotherapy or insulin in combination with one or two oral drugs. After glucose levels were well controlled, insulin and oral drugs were discontinued in a stepwise manner. The prolonged and partial remission rates were calculated and the possible factors contributing to remission were also analyzed. A total of 164 subjects completed the research study. The prolonged remission, partial remission and non-remission rates at the 5-year follow-up were 9.8, 59.8, and 30.5%, respectively. The remission rate was negatively correlated with disease duration (r=0.39). The combined rate of remission (prolonged and partial remission) significantly decreased when the duration was longer than 16 days, and reduced to approximately 50% after 1 month. Moreover, 75% of prolonged remission patients had duration of < 16 days. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. Furthermore, the duration after diagnosis is an independent predictor of remission rate, and initiation of short-term premixed insulin therapy within the first 16 days of diabetes diagnosis is very important for remission. This is the first study to evaluate the remission rate associated with short-term premixed insulin therapy in recently diagnosed type 2 diabetes outpatients. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. The duration of diabetes was identified as an independent predictor of drug-free remission. The initiation of short-term premixed insulin therapy within 15 days of diabetes onset is particular importance for remission.

Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway.

Proximal renal tubular damage is a critical process underlying diabetic kidney disease (DKD). Our previous study shows that prostaglandin E1 (PGE1) reduces the apoptosis of renal tubular cells in DKD rats. But its underlying mechanisms remain unclear. In this study we investigated the protective effects of PGE1 in DKD rats and high glucose (HG, 30 mM)-treated HK-2 proximal tubular cells. Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established, the DKD rats were administered PGE1 (10 µg· kg-1· d-1, iv.) for 10 consecutive days. We showed that PGE1 administration did not change blood glucose levels, but alleviated diabetic kidney injury in the DKD rats, evidenced by markedly reduced proteinuria and renal tubular apoptosis. In the in vitro experiments, PGE1 (0.1-100 µM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 µM) significantly suppressed the c-Jun N-terminal kinase (JNK) and the mitochondrial apoptosis-related protein expressions such as Bim, Bax, caspase-3 and cleaved caspase-3; similar changes were also observed in the kidney of PGE1-treated DKD rats. By using two pharmacological tools-JNK activator anisomycin (AM) and JNK inhibitor SP600125, we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells; JNK was an upstream regulator of Bim. In conclusion, our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling pathway.

Efficacy of low-protein diet for diabetic nephropathy: a systematic review of randomized controlled trials.

BACKGROUND: A low-protein diet (LPD) is believed to be beneficial in slowing the progression of kidney disease. It is reported that low protein diet can improve protein, sugar and lipid metabolism, and reduce the symptoms and complications of renal insufficiency. However, there has been controversial regarding the effects of protein restriction on diabetic nephropathy (DN). OBJECTIVE: To investigate the efficacy of LPD on renal function in patients with type 1 or 2 DN by meta-analysis of randomized controlled trials (RCTs). DESIGN: PubMed, MEDLINE, EMBASE and China National Knowledge Infrastructure databases were searched. Eleven randomized controlled trials met the inclusion criteria, of which 10 were English and 1 was Chinese. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was a change in proteinuria. Random-effects models were used to calculate the standardized mean difference (SMD) and the corresponding 95% confidence intervals (CI). Subgroup analyses were also performed. RESULTS: Our research indicated that LPD was not associated with a significant improvement in GFR (1.59 ml · min-1 · 1.73 m-2, 95% CI -0.57, 3.75, I2 = 76%; p = 0.15). This effect was consistent across the subgroups regardless of type of diabetes, course of diabetes and intervention period. Our results also showed that there was no significant difference on improvement of proteinuria in patients of LPD and those in normal-protein diet groups (- 0.48, 95%CI-1.70, 0.74, I2 = 94%, p = 0.44). Subgroup analysis revealed that LPD resulted in increased excretion of proteinuria in patients with type 2 diabetes (1.32, 95% CI 0.17, 2.47, I2 = 86%, p = 0.02). CONCLUSION: The present research showed that LPD was not significantly associated with improvement of renal function in patients with either type 1 or 2 diabetic nephropathy. Although these results do not completely eliminate the possibility that LPD is beneficial for patients with diabetic nephropathy, it does not seem to be significant benefit to renal function.

Experiments on Chloride Binding and Its Release by Sulfates in Cementitious Materials.

The aim of this study was to experimentally investigate the process of chloride binding and its sulfate-induced release in cementitious materials. The cementitious materials were replaced with hardened cement paste particles (HCPs) with water-to-cement ratios (w/c) of 0.35 and 0.45. A long-term immersion experiment of HCPs in 0.1 M sodium chloride solution was performed to investigate its chloride-binding capacity, and then it was immersed in sodium sulfate solutions with concentrations of 0.1 and 0.5 M to explore the release of chloride binding induced by sulfates. Silver nitrate titration and quantitative X-ray diffraction (QXRD) were used to measure the concentration of free chlorides in the solutions and the content of bound chlorides in HCPs, respectively. The results show that there is a higher chloride-binding capacity in HCPs with a w/c ratio of 0.45 compared to 0.35, and the content of chemically bound chlorides is associated with the formation and decomposition of Friedel's and Kuzel's salts in HCPs. The presence of sulfates can easily result in the release of bound chlorides in Friedel's salt, but it cannot cause a complete release of bound chlorides in Kuzel's salt. Physically bound chlorides are more easily released by sulfates than chemically bound chlorides, and a high w/c ratio or sulfate concentration can increase the release rate of bound chlorides in HCPs.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

[Influences of nevirapine on cell proliferation and expression of sodium/iodide symporter in human anaplastic thyroid carcinoma cell line].

OBJECTIVE: To explore the effects of nevirapine on the proliferation and expression of sodium-iodide symporter (NIS) mRNA in FRO cells in vitro. METHODS: The cells were incubated in different concentrations of nevirapine to evaluate the cell growth rate. And the expressions of NIS mRNA and TSHR mRNA were determined by real-time quantitative reverse polymerase chain reaction. RESULTS: Cell proliferation was inhibited after a 96 h nevirapine treatment. After incubating in the presence of 200 and 350 µmol/L nevirapine, the expression of NIS mRNA was (1.39 ± 0.04) and (1.85 ± 0.28) times versus the control cells (P < 0.01) while the expressions of TSHR mRNA was (2.23 ± 1.47) and (2.83 ± 0.78) times versus the control cells respectively (both P < 0.05). CONCLUSION: Nevirapine inhibits cell proliferation in FRO cell line. More importantly, the cells exposed to nevirapine may induce the up-regulations of NIS mRNA and TSHR mRNA.

Cdc42 upregulation under high glucose induces podocyte apoptosis and impairs ß-cell insulin secretion.

Objectives: The progressive impairment of ß-cell function results in prolonged deterioration in patients with type 2 diabetes mellitus (T2DM). Interestingly, the finding on pancreatitis secondary to renal injury suggests that potential communication exists between kidney and pancreas. Therefore, we aimed to investigate cell division cycle 42 (Cdc42)-mediated podocyte apoptosis and its effect on insulin secretion in islet ß-cells. Methods: Type 2 diabetic nephropathy mouse models were established to identify the expression of Cdc42 in podocytes by immunohistochemistry. An in vitro co-culture of mouse podocyte MPC5 and ß-TC6 cells was preliminarily established. Subsequently, podocyte apoptosis induced by high glucose and Cdc42 was detected by TUNEL staining and western blotting. In addition, the JNK pathway was examined to determine the mechanism of apoptosis in MPC5 cells. Finally, insulin secretion and expression in ß-TC6 cells as well as malondialdehyde (MDA) and superoxide dismutase (SOD) levels in both cell types were examined after the regulation of Cdc42 in MPC5 cells. Results: Cdc42 was highly expressed in the podocytes of diabetic nephropathy mice. Exposure to 25 mM glucose for 48 h induced a significant upregulation of Cdc42, Bax, and cleaved caspase-3 as well as a decreased Bcl-2 expression. In addition, marked apoptosis of MPC5 cells was observed compared to normal glucose treatment. After transfection with Cdc42 plasmid, apoptosis of MPC5 cells was enhanced with an increased expression of p-JNK, whereas inhibition of Cdc42 significantly alleviated podocyte apoptosis accompanied by a downregulation of p-JNK. The glucose-stimulated insulin secretion level of ß-TC6 cells decreased after the upregulation of Cdc42 in MPC5 cells. Immunofluorescence staining for insulin showed that co-culture with MPC5 cells carrying the Cdc42 plasmid significantly reduced insulin expression, whereas inhibition of Cdc42 in MPC5 cells alleviated the above-mentioned abnormality of ß-TC6 cells. The expression of Cdc42 and p-p38 in ß-TC6 cells increased following the upregulation of Cdc42 in MPC5 cells; this was concurrent with augmented MDA levels and decreased SOD activity. The opposite result was observed for Cdc42 knockdown in MPC5 cells. Conclusions: Cdc42 in podocytes plays a crucial role in insulin secretion by ß-cells, which may provide a new therapeutic target to prevent the vicious cycle of ß-cell dysfunction in T2DM.

[Therapeutic effects of (131)I therapy on hyperthyroidism in adolescents and adults: a comparative study].

OBJECTIVE: To investigate the efficacy and safety of (131)I therapy on hyperthyroidism in adolescents, middle-aged people, and the elderly. METHODS: 940 patients with hyperthyroidism, 106 aged < 25 (Group A, group of young people), 768 aged 25 - 60 (Group B, middle-aged group), and 66 aged > 60 (Group C, group of the elderly), underwent (131)I therapy and were followed up for 2 years to evaluate the efficacy and safety. RESULTS: Forty-six patients in group A (43.4%) became euthyroid, 34(32.1%) turned better, 24 (22.6%) suffered from hypothyroidism, and 2 (1.9%) remained un-changed, with a general effective rate of 98.11% (104/106). 346 patients (45.1%) in Group B became euthyroid, 260 (33.9%) turned better, 140 (18.2%) suffered from hypothyroidism, and 22 (2.9%) remained un-changed, with a general effective rate of 97.14% (746/768). And 28 patients (42.4%)in Group C became euthyroid, 24 (36.4%) turned better, 10 (15.15%) suffered from hypothyroidism, and 4 (6.1%) remained unchanged, with a general effective rate of 93.93% (62/66). There were not significant differences in the recovery rate, improvement rate, hypothyroidism rat, and ineffective rate among the 3 groups (all P > 0.05). CONCLUSION: There are no significant differences in the efficacy and safety of (131)I therapy in hyperthyroidism on the patients of different ages, including adolescent, adult and elder persons. (131)I therapy is safe and effective for adolescents.

[Effects of sarcoplasmic reticulum calcium ATPase 2a overexpression on endoplasmic reticulum stress in cardiomyocytes].

OBJECTIVE: To investigate the effects of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) overexpression on the endoplasmic reticulum stress (ERS). METHODS: Ventricular cardiomyocytes were obtained from a neonatal rat, cultured, and then randomly divided into 6 groups: normal control group; hypoxia group cultured in an airtight chamber gassed with 95% N(2)/5% CO2 at 37 degrees C for 72 hours so as to induce ERS; tunicamycin group treated with 10 microg/ml tunicamycin so as to induce ERS too; SERCA2a group transfected with recombinant adenovirus expressing the target gene SERCA2a (rAd-SERCA2a); SERCA2a + hypoxia group; and SERCA2a + tunicamycin group. Western blotting was used to detect the protein expression of SERCA2a, and glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), both the ERS markers. Flow cytometry was used to detect the apoptosis of the cardiomyocytes, and trypan blue staining was used to detect the survival rate of the cardiomyocytes. RESULTS: (1) The GRP78 expression level of the hypoxia group was 5.1 times as high as that of the control group, and the CHOP expression level of the hypoxia group was 2.5 times as high as hat of the control group. The GRP78 expression level of the tunicamycin group was 4.9 times as high as that of the control group, and the CHOP expression level of the tunicamycin group was 3.1 times as high as hat of the control group. SERCA2a overexpression was found to relieve the expression of GRP78 induced by hypoxia and tunicamycin (49.1% and 50.4% decrease respectively), and to inhibit the activation of CHOP (52.7% and 66.1% decrease respectively). (2) In comparison with the hypoxia group, the protein expression levels of GRP78 and CHOP of the SERCA2a overexpression + hypoxia group were significantly lower by 49.1% and 52.7% respectively, the apoptotic rate was significantly lower by 66.0%, and the cardiomyocyte survival rate was significantly higher by 13.4% (all P < 0.05). Compared with the tunicamycin group, the protein expression levels of GRP78 and CHOP of the SERCA2a overexpression + tunicamycin group were significantly lower by 50.4% and 66.1% respectively, the apoptotic rate was significantly lower by 54.0%, and the cardiomyocyte survival rate was significantly higher by 6.7% (all P < 0.05). CONCLUSION: SERCA2a overexpression attenuates ERS induced by hypoxia or tunicamycin, and protects cardiomyocytes against ERS-mediated cellular injury.

Enhancing Medium-Chain Fatty Acid Ethyl Ester Production During Beer Fermentation Through EEB1 and ETR1 Overexpression in Saccharomyces pastorianus.

Esters are important flavor compounds in alcoholic beverages. Although they are present at trace levels, esters play a key role in the formation of flavors, especially fruity flavors, in beverages. Low ester contents result in bland beer and unpleasant flavor. In this study, three recombinant strains, ethanol O-acyltransferase encoding EEB1 overexpression strain (31194:: EEB1), 2-enoyl thioester reductase encoding ETR1 overexpression strain (31194:: ETR1), and EEB1- ETR1 co-overexpression strain (31194:: EEB1:: ETR1), were constructed. Ethyl hexanoate production by 31194:: EEB1 and 31194:: EEB1:: ETR1 was 106% higher than that by the parental strain. Further, ethyl octanoate production by 31194:: EEB1 and 31194:: EEB1:: ETR1 was enhanced by 47 and 41%, respectively, compared with that of parental strain 31194. However, no difference was observed between 31194:: ETR1 and the parental strain in terms of ethyl hexanoate and ethyl octanoate production. This indicates that although EEB1 overexpression in Saccharomyces pastorianus enhanced ethyl hexanoate and ethyl octanoate production, ETR1 expression levels did not affect the extracellular concentrations of these esters.

Efficacy and short-term side effects of sitagliptin, vildagliptin and saxagliptin in Chinese diabetes: a randomized clinical trial.

AIMS: To investigate the difference in the efficacy among dipeptidyl peptidase-4 (DPP-4) inhibitors in Chinese adults with newly diagnosed diabetes. MATERIALS AND METHODS: In a multicenter, randomized study, we enrolled adults who were either treatment naive or off prior anti-hyperglycemic therapy for at least 3 months. Eligible patients had hemoglobin A1c (HbA1c) concentrations of 6.5-9.5%. Three hundred patients had been randomly allocated to sitagliptin 100 mg, once daily; vildagliptin 50 mg, twice daily and saxagliptin 5 mg, once daily for 12 weeks. Patients and investigators were masked to treatment assignment. The primary endpoint was change from baseline in HbA1c at week 12. This study was completed and registered with ClinicalTrials.gov, number NCT01703637. RESULTS: Totally 277 patients were enrolled in the final analysis, and 93 patients received sitagliptin, 94 received vildagliptin and 90 received saxagliptin. Compared with baseline, adjusted mean differences in change from baseline HbA1c at week 12 were -0.50% (95% CI: -0.20 to -0.90), -0.65% (95% CI: -0.40 to -1.40), -0.70 (95% CI: -0.50 to -1.00) for sitagliptin, vildagliptin and saxagliptin group, respectively. The overall HbA1c-lowering effect was similar for all three selected DPP-4 inhibitors after adjustment for age and baseline HbA1c. Notably, in secondary outcome analysis, patients in vildagliptin group showed a significant decrease in total cholesterol levels, compared with participants in sitagliptin and saxagliptin groups. No significant between-group difference was shown in adverse events (AE). CONCLUSIONS: The overall HbA1c-lowering effect and incidence of AE were similar for sitagliptin, vildagliptin and saxagliptin in Chinese adults with newly diagnosed diabetes.

Rigorous proof for the nonlocal correlation function in the transverse Ising model with ring frustration.

An unusual correlation function was conjectured by Campostrini et al. [Phys. Rev. E 91, 042123 (2015)PLEEE81539-375510.1103/PhysRevE.91.042123] for the ground state of a transverse Ising chain with geometrical frustration. Later, we provided a rigorous proof for it and demonstrated its nonlocal nature based on an evaluation of a Toeplitz determinant in the thermodynamic limit [J. Stat. Mech. (2016) 11310210.1088/1742-5468/2016/11/113102]. In this paper, we further prove that all the low excited energy states forming the gapless kink phase share the same asymptotic correlation function with the ground state. As a consequence, the thermal correlation function almost remains constant at low temperatures if one assumes a canonical ensemble.

Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro.

BACKGROUND: Stem cells, which have the ability to differentiate into insulin-producing cells (IPCs), would provide a potentially unlimited source of islet cells for transplantation and alleviate the major limitations of availability and allogeneic rejection. Therefore, the utilization of stem cells is becoming the most promising therapy for diabetes mellitus (DM). Here, we studied the differentiation capacity of the diabetic patient's bone marrow-derived mesenchymal stem cells (MSCs) and tested the feasibility of using MSCs for beta-cell replacement. METHODS: Bone marrow-derived MSCs were obtained from 10 DM patients (5 type 1 DM and 5 type 2 DM) and induced to IPCs under a three-stage protocol. Representative cell surface antigen expression profiles of MSCs were analysed by flow cytometric analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect multiple genes related to pancreatic beta-cell development and function. The identity of the IPCs was illustrated by the analysis of morphology, ditizone staining and immunocytochemistry. Release of insulin by these cells was confirmed by immunoradioassay. RESULTS: Flow cytometric analysis of MSCs at passage 3 showed that these cells expressed high levels of CD29 (98.28%), CD44 (99.56%) and CD106 (98.34%). Typical islet-like cell clusters were observed at the end of the protocol (18 days). Ditizone staining and immunohistochemistry for insulin were both positive. These differentiated cells at stage 2 (10 days) expressed nestin, pancreatic duodenal homeobox-1 (PDX-1), Neurogenin3, Pax4, insulin, glucagon, but at stage 3 (18 days) we observed the high expression of PDX-1, insulin, glucagon. Insulin was secreted by these cells in response to different concentrations of glucose stimulation in a regulated manner (P<0.05). CONCLUSIONS: Bone marrow-derived MSCs from DM patients can differentiate into functional IPCs under certain conditions in vitro. Using diabetic patient's own bone marrow-derived MSCs as a source of autologous IPCs for beta-cell replacement would be feasible.

[Distribution of polymorphism in endothelial nitric oxide synthase gene in Singapore Chinese and its association with diabetic nephropathy].

OBJECTIVE: To examine the distribution of intron 4 polymorphism in endothelial nitric oxide synthase (eNOS) gene in mainland Chinese and Singapore Chinese and its association with diabetic nephropathy (DN). METHODS: Peripheral blood samples were collected from 237 diabetes patients with the diabetic duration longer than 10 years, 87 mainland Chinese who visited the Qilu Hospital, Shandong province, and diabetic duration and blood sugar control-matched 150 Singapore Chinese who visited the Singapore National University Hospital. DNA extraction, PCR, cloning, and sequencing were conducted. RESULTS: The 27 bp repeat polymorphism in intron 4 was tri allelic (a, b, and c alleles) in the Singapore Chinese while biallelic (a and b alleles) in the mainland Chinese. A third allele-allele c, with six 27 bp repeats was found. Significant difference was identified in the a allele distribution between the mainland and the Singapore Chinese (P < 0.001), but the intron 4 polymorphism didn't show any association with DN. CONCLUSION: The intron 4 polymorphism is tri allelic, and the a allele distribution is not significantly associated with DN.

High glucose induces apoptosis via upregulation of Bim expression in proximal tubule epithelial cells.

Diabetic nephropathy is the primary cause of end-stage renal disease. Apoptosis of tubule epithelial cells is a major feature of diabetic nephropathy. The mechanisms of high glucose (HG) induced apoptosis are not fully understood. Here we demonstrated that, HG induced apoptosis via upregulating the expression of proapoptotic Bcl-2 homology domain 3 (BH3)-only protein Bim protein, but not bring a significant change in the baseline level of autophagy in HK2 cells. The increase of Bim expression was caused by the ugregulation of transcription factors, FOXO1 and FOXO3a. Bim expression initiates BAX/BAK-mediated mitochondria-dependent apoptosis. Silence of Bim by siRNA in HK2 cells prevented HG-induced apoptosis and also sensitized HK2 cells to autophagy during HG treatment. The autophagy inhibitor 3-MA increased the injury in Bim knockdown HK2 cells by retriggering apoptosis. The above results suggest a Bim-independent apoptosis pathway in HK2 cells, which normally could be inhibited by autophagy. Overall, our results indicate that HG induces apoptosis via up-regulation of Bim expression in proximal tubule epithelial cells.

Calcium Dobesilate Prevents Diabetic Kidney Disease by Decreasing Bim and Inhibiting Apoptosis of Renal Proximal Tubular Epithelial Cells.

Apoptosis of renal proximal tubular epithelial cells (PTECs) plays a vital role in the pathogenesis and progression of diabetic kidney disease (DKD). Calcium dobesilate is a vascular protective compound used for treatment of diabetic retinopathy and chronic venous insufficiency. The aim of this study was to determine whether calcium dobesilate can protect PTECs from glucose-induced apoptosis and the potential mechanism of this effect. It is indicated that high glucose promoted abnormal apoptosis of HK2 cells, which was inhibited by treatment of calcium dobesilate, while Bim expression decreased in response to calcium dobesilate in high-glucose-treated HK2 cells. These findings confirmed the therapeutic effects of calcium dobesilate on DKD and emphasized the importance of it as a potentially crucial drug in treatment of DKD.

Effect of Hydraulic Retention Time on Anaerobic Digestion of Wheat Straw in the Semicontinuous Continuous Stirred-Tank Reactors.

Three semicontinuous continuous stirred-tank reactors (CSTR) operating at mesophilic conditions (35°C) were used to investigate the effect of hydraulic retention time (HRT) on anaerobic digestion of wheat straw. The results showed that the average biogas production with HRT of 20, 40, and 60 days was 46.8, 79.9, and 89.1 mL/g total solid as well as 55.2, 94.3, and 105.2 mL/g volatile solids, respectively. The methane content with HRT of 20 days, from 14.2% to 28.5%, was the lowest among the three reactors. The pH values with HRT of 40 and 60 days were in the acceptable range compared to that with HRT of 20 days. The propionate was dominant in the reactor with HRT of 20 days, inhibiting the activities of methanogens and causing the lower methane content in biogas. The degradation of cellulose, hemicellulose, and crystalline cellulose based on XRD was also strongly influenced by HRTs.