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A cobalt (Co)-doped perovskite molybdenum trioxide (α-MoO

Objective: We aimed to analyze the clinical characteristics of peritoneal dialysis (PD) patients with different baseline peritoneal transport characteristics and the effect of peritoneal transport characteristics on prognosis of PD patients.Methods: Patients who received PD for over 1 months in the Nanjing Drum Tower Hospital between January 2006 and December 2019 were included. They were divided into four groups according to the baseline dialysate/plasma creatinine (D/Pcr) value. The clinical characteristics, changes in peritoneal transport, and risk factors of death and technique failure were analyzed.Results: A total of 323 patients were enrolled, comprising 70 patients in the low transport group, 135 in the low average transport group, 101 in the high average transport group, and 17 in the high transport group. Multivariate logistic regression analysis suggested that male sex (OR = 1.529, 95%CI 1.003–2.330) and low albumin levels (OR = 0.910, 95%CI 0.869–0.952) were risk factors for baseline high peritoneal transport status. The survival rate in the high transport group was significantly lower than that of the low transport (χ2 = 3.953, P = 0.047), LA (χ2 = 4.355, P = 0.037) and high average transport groups (χ2 = 9.359, P = 0.002). There was no significant difference in technique failure rate among these four groups (χ2 = 0.107, P = 0.991). Multivariate Cox regression analysis suggested that age (HR = 1.053, 95%CI 1.026–1.082), Charlson's comorbidity index (HR = 1.630, 95%CI 1.307–2.032), and baseline high transport (HR = 3.280, 95%CI 1.109–9.699) were independent risk factors for patient death. Male sex (HR = 1.851, 95%CI 1.123–3.052), C-reactive protein levels (HR = 1.008, 95%CI 1.001–1.015), and peritonitis (HR = 2.312, 95%CI 1.430–3.739) were independent risk factors for technique failure.Conclusions: Initial high peritoneal transport status is an independent risk factor for patient death. Male sex and low albumin levels were determinants of baseline high peritoneal transport.

Hepatocellular carcinoma (HCC) is known as the fifth most common cancer in the world for its poor prognosis. New diagnostic markers and treatments are urgent to discover. To evaluate the protein expression of Tropomyosin4 (TPM4) and investigate its prognostic value in HCC, we collected 110 patients with different degrees of HCC and 10 patients with normal hepatic tissues and performed immunohistochemistry. Western bot was used to evaluate the expression of TPM4 in three HCC cell lines (HepG2, Huh7, SMMC-7721) and normal liver cell line LO2, as well as 7 HCC tissues and 7 normal hepatic tissues. The results of TPM4 staining revealed that TPM4 expression in HCC was higher than that in normal hepatic tissues, which was positive in 51.8% (n=57) and negative in 48.2% (n=53) while in normal hepatic tissues positive staining was in 10% (n=1) and negative staining was in 90% (n=9) (P=0.011). And the expression of TPM4 was related to pT status, grade and stage (P

Introduction and objectives: Eukaryotic translation initiation factor 5A (EIF5A) is a member of the identified eIF family and played an important role in cell proliferation. There are few studies about the correlation between EIF5A and hepatocellular carcinoma (HCC). Materials and methods: We evaluated the expression of the EIF5A in human HCC cell lines and tissues by western blot analysis. Immunohistochemistry analysis of EIF5A was performed on a tissue microarray including 10 normal liver samples and 90 pathological section of HCC. Receiver operating characteristic (ROC) was introduced to obtain an optimal cut-off score for EIF5A positive expression. Results: Western blot results showed that EIF5A was highly expressed in HCC cell lines and tissues. Based on ROC curve analysis, 1/10 (10.0%) of normal hepatic tissues and 67/90 (74.4%) of HCC tissues were tested positive for EIF5A expression, which indicated that EIF5A were significantly up-regulated in HCC tissues compared with normal liver tissues (χ2=17.177, P

To analyze the association of IL-1β with recurrence after the first epileptic seizure in ischemic stroke patients and evaluate its predictive value. 238 patients with the first epileptic seizure after ischemic stroke were included in this study. IL-1β expression levels were detected through quantitative Real-Time PCR. Kaplan–Meier method was used to perform univariate analysis with log-rank test. The variables with P

WRINKLED1 (WRI1), an APETALA2/ethylene-responsive-element-binding protein (AP2/EREBP) subfamily transcription factor, plays a crucial role in the transcriptional regulation of plant fatty acid biosynthesis. In this study

Background. Total knee arthroplasty is an effective treatment for end-stage knee arthritis. Studies’ date have shown that the demand for knee replacements continues to increase worldwide. Although racial disparities have been previously reported in the utilization of total knee arthroplasty in western countries, however, there are few similar studies in China. Objectives. Retrospective analysis of medical records identified the characteristics of Tibetan patients who had undergone total knee arthroplasty living in plateau and their differences with Hans living in Sichuan Basin. Methods. The patients with unilateral primary total knee arthroplasty in Sichuan Orthopedic Hospital from 2015 to 2020 were enrolled. Analyze and compare the demographic characteristics (age, body mass index, and occupation) and pathogenesis characteristics (disease duration, exacerbation period, treatment methods, etc.) of the plateau Tibetans and the Hans of the Sichuan Basin. Results. 1595 eligible patients were reviewed, including 541 Tibetan patients and 1054 Han patients, The average age of Tibetan patients was lower than that of Han patients ( P < 0.001 ); the average BMI index of Tibetan patients was higher than that of Han patients ( P < 0.001 ). And obese people account for more; the occupational distribution of Tibetan patients is more concentrated, mainly farmers. Tibetan patients have a longer course of disease than Han patients ( P < 0.001 ). Conclusions. The social background and geographical environment of the Tibetan population are different from those of the Han. Tibetans living on plateaus have an earlier illness, a longer course of illness, a more obvious trend of younger, age and fewer opportunities for regular treatment during the illness.

Gram-negative bacterial infection causes many bone diseases such as osteolysis, osteomyelitis and septic arthritis. Lipopolysaccharide (LPS), a bacteria product, played an important role in this process. Drugs that inhibited LPS-induced osteoclastogenesis were urgently needed for the prevention of bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis.tinctoria, which possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic and anti-diabetic effects. In this study, the effect of marein on RAW264.7 cells was measured by CCK-8 assay; TRAP staining was used to determine osteoclastogenesis; the levels of osteoclast-related genes and NF-κB-related proteins were analyzed by WB; the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation from osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes including RANK, TRAF6, MMP-9, CK and CAⅡ. Besides, marein treatment could inhibit LPS-induced activation of NF-κB signaling pathway in RAW264.7 cells. Meanwhile, inhibition of NF-κB signaling pathway decreased the formation of osteoclasts and expression of pro-inflammatory cytokines which were LPS-induced. Collectively, marein could prevent LPS-induced osteoclast formation in vitro by regulating NF-κB signaling pathway. These findings provided evidence that marein might be beneficial as a valuable choice for the prevention and treatment of bacteria-induced bone destruction disease, and gave new insights for understanding its possible mechanism.

Background End stage renal disease (ESRD) has caused public health problem with high prevalence worldwide. Peritoneum from peritoneal dialysis patients with ESRD can induce pathological changes of the peritoneum, including fibrosis. The trans-differentiation of pericytes has been found to be closely associated with inflammatory diseases, such as organ fibrosis. However, the function of macrophages in regulating the transition of pericyte to peritoneal fibrosis is unclear. Methods Histological examination was conducted using Hematoxylin and eosin (HE) staining and Masson’s trichrome staining. The protein levels were determined via western blot. Enzyme-linked immunosorbent assay (ELISA) was used to examine IL-1β concentrations. Gasdermin D (GSDMD) was knocked out in mice by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9 (CRISPR-Cas9). Results Mice receiving dextrose peritoneal dialysate displayed mesothelial cell monolayer loss and thickness of submesothelial compact zone increase. Moreover, dextrose peritoneal dialysate treatment up-regulated GSDMD expression. GSDMD knockdown inhibited IL-1β production in macrophages. Further, pericytes were treated with cultural supernatant from macrophages. We found that GSDMD knockdown suppressed fibrosis and vascular endothelial growth factor (VEGF)/phosphoinositide 3-kinase (PI3K) pathway in pericytes. In addition, GSDMD were knocked out in mice using CRISPR/Cas9. The histological examinations revealed that GSDMD−/− alleviated the damage of peritoneal tissue and thickness of submesothelial compact zone. GSDMD−/− attenuated interleukin-1beta (IL-1β) level and peritoneal fibrosis induced by dextrose peritoneal dialysate treatment in pericytes in vivo. Conclusion These results demonstrated that macrophages can regulate the transition of pericyte to peritoneal fibrosis via the GSDMD/IL-1β axis, which provides a new therapeutic target.

Polyethylenimine (PEI) is a promising delivery vector of nucleic acids, but cytotoxicity and only moderate transfection efficacy with small RNAs limit its applications. Here we hypothesized that hydrophobization of PEI by combined modification with perfluorinated moieties (F) and cholesterol (Ch) will help in addressing both the cytotoxicity and siRNA delivery efficacy. To test the hypothesis, we synthesized a series of copolymers (F-PEI-Ch) by modifying PEI by reaction with heptafluorobutyric anhydride and cholesteryl chloroformate. We investigated and compared the effect of the modifications on siRNA delivery in vitro and in vivo. We found that the F-PEI-Ch copolymers assembled into micellar structures and that the copolymer with the highest Ch content exhibited the best siRNA delivery performance, including lower cytotoxicity, enhanced cell uptake, improved endosomal escape, and the best siRNA silencing efficacy in vitro and in vivo when compared with control PEI, F-PEI, and PEI-Ch. Overall, hydrophobization of PEI with a combination of cholesterol and superhydrophobic perfluorinated moieties represents a promising approach to the design of siRNA delivery vectors with decreased toxicity and enhanced transfection efficacy.

In recent years, T-type three-level inverter (TLI) has attracted attentions due to its advantages, such as simple structure and higher efficiency. Neutral point voltage (NPV) is very critical for its normal operation, and the necessary conditions of maintaining NPV balance respectively in a switching cycle and in a fundamental cycle are simply reviewed in this paper. With the increment of power switches, the reliability of T-type TLI becomes particularly important. When switch faults occur, fault-tolerant control strategies are usually adopted. However, in existing literatures, it is unknown whether the NPV balance can be still maintained under different fault types. Therefore, the application range of a fault-tolerant control is also unknown. In this paper, based on the necessary conditions of maintaining NPV balance, the application ranges of two representative fault-tolerant control strategies are revealed under different open-circuit (OC) fault types in inner switch. It found that the application ranges are closely related to the modulation index, load power factor (PF) and OC fault type. Finally, the correctness of the theoretical analysis is verified by the experimental results.

The traditional discontinuous pulse width modulation (DPWM) strategy is very suitable for reducing the switching losses of three-level inverter (TLI). However, large neutral point voltage (NPV) fluctuation is usually caused, which results in low frequency harmonics (LFHs) in the output line voltage. Therefore, a DPWM modulation strategy that can suppress LFHs is presented in this paper, and it is recorded as low frequency harmonic reduction DPWM (LFHRDPWM). The proposed LFHRDPWM can be seen as an improvement of traditional DPWM, which modifies the duty ratios according to voltages of the two DC-link capacitors. For LFHRDPWM, due to the suppressed LFHs, the self-balancing ability of NPV is thus lost, and gradually increased DC offset on NPV is caused. To overcome that, an active neutral point voltage control (ANPVC) method is also proposed. The proposed methods not only can achieve switching loss (SL) reduction almost as the same as traditional DPWM strategy, but also can realize NPV control and LFHs reduction. The effectiveness of the proposed method is verified by experiments.

Objectives: To improve the mouse model of relief for unilateral ureteral obstruction (RUUO) and explore the pathological process of renal fibrosis after the obstruction was relieved. Methods: C57BL/6 mice in model group were randomly divided into RUUO group, improved RUUO group, and UUO group. After leaving Unilateral Ureteral Obstruction (UUO) for 3 days, the obstruction was released by reimplantation way in RUUO group and in reimplantation + catheter way in improved RUUO group. C57BL/6 mice in observation group were randomly divided into 1d RUUO group, 3d RUUO group, 7d RUUO group, and 14d RUUO group. Three days after UUO, the obstruction was released by reimplantation + catheter in four groups. We detected the renal volume, H&E, Masson staining, and immunohistochemistry of kidney pathology on the seventh day after RUUO in model group and on the 1st, 3rd, 7th, and 14th day after RUUO in observation group. Results: Comparing with mice in RUUO group, mice in improved RUUO group had lower renal volume, tubular damage score, and collagen area percentage. After the obstruction was relieved, the renal volume decreased gradually within 2 weeks. The tubular damage score in 7d RUUO group was lower than that in 1d RUUO and 3d RUUO group. However, the tubular damage score in 14d RUUO group was higher than that in 7d RUUO group. The tendency of collagen area percentage and α-SMA IOD value were consistent with the tubular damage score. Conclusions: Using the method of reimplantation + catheter, a reliable mice model of RUUO can be got. After RUUO, the de-obstructed kidneys are still in damage and fibrosis state.

OBJECTIVE: To investigate the safety and effectiveness of low-dose tranexamic acid (TXA) in operation of multi-level continuous thoracic ossification of ligament flavum (TOLF). METHODS: A clinical data of 26 patients who underwent operation for multi-level continuous TOLF and met the selection criteria between July 2015 and January 2019 was retrospectively analyzed. Among them, 13 cases (group A) were received intravenous infusion of TXA (10 mg/kg) at 15 minutes before operation, and maintained the infusion at 1 mg/(kg·h) until the end of the operation; 13 cases (group B) were received the same dose of normal saline before and during operation. There was no significant difference in gender, age, body mass index, diseased segment, and preoperative hemoglobin, platelet count, activated partial thromboplastin time, prothrombin time, international normalized ratio (INR) between the two groups (P>0.05). The hemoglobin, platelet count, activated partial thromboplastin time, prothrombin time, INR, the number of deep vein thrombosis of the lower extremities, operation time, intraoperative blood loss, postoperative drainage volume, total blood loss, and the time of drainage tube extubation in the two groups were recorded and compared. RESULTS: All operations in the two groups were successfully completed. Compared with group B, the operation time and time of drainage tube extubation in group A were shortened, and the intraoperative blood loss, postoperative drainage volume, and total blood loss were reduced. The differences between the two groups were significant (P0.05). CONCLUSION: In multi-level continuous TOLF operation, intravenous administration of low-dose TXA can effectively reduce blood loss, shorten postoperative drainage time, and does not increase the risk of complications.

Peritoneal dialysis (PD)-related peritoneal fibrosis (PF) is characterized by progressive extracellular matrix (ECM) accumulation in peritoneal mesothelial cells (PMCs) during long-term use of high glucose (HG)-based dialysates. Activation of the renin-angiotensin system (RAS) has been shown to be associated with PF. The aim of this study was to explore the underlying mechanism of the RAS in HG-induced PF. We treated C57BL/6 mice and a human PMC line with HG to induce a PF model and to stimulate ECM accumulation, respectively. RAS activity was blocked using valsartan or angiotensin II (ANGII) type 1 receptor siRNA. The major findings were as follows. First, mice in the HG group exhibited increased collagen deposition and expression of ECM proteins, including α-smooth muscle actin (α-SMA) and collagen type I in the peritoneum. Consistent with the in vivo data, HG upregulated α-SMA expression in human peritoneal mesothelial cells (HPMCs) in a time- and dose-dependent manner. Second, HG stimulation led to RAS activation in HPMCs, and inactivation of RAS decreased the expression of ECM proteins in vivo and in vitro, even during HG stimulation. Finally, RAS-mediated ECM production was associated with lipid accumulation in HPMCs and depended on the dysregulation of the low-density lipoprotein receptor (LDLr) pathway. HG-stimulated HPMCs showed increased coexpression of LDLr and α-SMA, whereas blockade of RAS activity reversed the effect. Furthermore, inhibition of LDLr signaling decreased α-SMA and collagen type I expression in HPMCs when treated with HG and ANG II. In conclusion, increased intracellular RAS activity impaired lipid homeostasis and induced ECM accumulation in HPMCs by disrupting the LDLr pathway, which contributed to PF.

Additional file of Predictive value of live birth rate based on different intrauterine adhesion evaluation systems following TCRA

Additional file 1: Table S1. The American Fertility Society (AFS) classification of intrauterine adhesions, 1988. Table S2. Classification by March 1978. Table S3. European Society of Gynecological Endoscopy (ESGE) classification of IUAs (1995 version). Table S4. Scoring by Nasr 2000. Table S5. Chinese intrauterine adhesions diagnosis classification criteria in 2015.

BackgroundLipopolysaccharide (LPS), a bacteria product, plays an important role in orthopedic diseases. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed for the prevention of bone destruction.MethodsIn this study, we evaluated the effect of β-ecdysterone (β-Ecd), a major component of Chinese herbal medicines derived from the root of Achyranthes bidentata BI on LPS-induced osteoclastogenesis in vitro and explored the mechanism underlying the effects of β-Ecd on this.ResultsWe showed that β-Ecd inhibited LPS-induced osteoclast formation from osteoclast precursor RAW264.7 cells. The inhibition occurred through suppressing the production of osteoclast activating TNF-α, IL-1β, PGE2 and COX-2, which led to down-regulating expression of osteoclast-related genes including RANK, TRAF6, MMP-9, CK and CAⅡ. Besides, β-Ecd treatment can inhibit LPS-induced activation of NF-κB signaling pathway in RAW264.7 cells. Meanwhile, inhibition of NF-κB signaling pathway decreased the formation of osteoclasts and expression of pro-inflammatory cytokines which LPS-induced. Collectively, β-Ecd can prevent LPS-induced osteoclast formation in vitro by regulating NF-κB signaling pathway.Conclusions These findings provide evidences that β-Ecd might be beneficial as a valuable choice for the prevention and treatment of bacteria-induced bone destruction disease, and give new insights for understanding its possible mechanism.

Objective: The aim of this study was to assess the predictive value of five different intrauterine adhesion (IUA) evaluation systems for live birth rate following transcervical resection of adhesion (TCRA).Method: This retrospective study included 128 women with IUA who desired for spontaneous conception after TCRA. All the patients were retrospectively scored by the American Fertility Society (AFS) classification, European Society of Gynecological Endoscopy (ESGE) classification, March’s classification (March), Nasr’s classification (Nasr) and Chinese IUA diagnosis classification criteria (Chinese). The predictive value of these evaluation systems was determined by receiver operating characteristic (ROC) curves and area under a ROC curve (AUC).Results: The correlation coefficients of AFS, ESGE, March, Nasr and Chinese classification and the live birth rate were 0.282, 0.324, 0.260, 0.418, 0.364, respectively. All five scoring systems were efficient to predict live birth rate. Among them, Nasr’s classification showed the highest AUC (0.748) with the best predictive value.Conclusion: AFS, ESGE, March, Nasr and Chinese classification were demonstrated to be capable of predicting live birth following TCRA, and Nasr’s classification showed the highest predictive value of live birth.

Maleimide liposomes capable of GSH depletion acted as the adjuvant for augmenting the photothermal immunotherapy of breast cancer., The high redox level of tumor microenvironment inhibits the oxidation treatment and the immune response. Here, we innovatively develop maleimide liposome (ML) adjuvants to promote immunogenic cell death (ICD) induction and dendritic cells (DCs) maturation by glutathione (GSH) depletion for augmenting the photothermal immunotherapy of breast cancer. The ML effectively depletes the intracellular GSH and up-regulates reactive oxygen species (ROS) in both tumor cells and DCs. In tumor cells, the ROS boosted the ABTS·+ production to activate photothermal-induced ICD. In DCs, it relieved the immunosuppression, promoting DC maturation (57%) and antigen presenting. As a result of the ML assistant, the therapeutic systems improved the infiltration of CD8+ T cells to 53% in tumor tissues, eliciting strong abscopal effect and antimetastasis effect. The MLs were believed to be a superior candidate of adjuvants for enhancing immune response and cancer therapeutic efficacy.

Built-up land in floodplains (BLF) is a driver and a disaster-bearing body of flood risk from a socio-hydrological perspective. The relationship between BLF growth and flood vulnerability is the key to understanding and managing flood risk. However, previous studies have focused more on the relationship between BLF growth and flood exposure, ignoring flood vulnerability. We examined the BLF expansion pattern (patch size and expansion type) in the North China Plain Area from 1975 to 2014 (1975–1990–2000–2014) using GIS (geographic information system)-based landscape analysis and revealed its relationship with flood vulnerability. The results show that the BLF area experienced rapid growth (288.26%) from dispersion to coalescence. Small patches dominated the number and area of BLF growth, and edge-expansion patches were the expansion type with the most area growth. We discovered that flood vulnerability was significantly correlated with the growth in small (R = 0.36, p < 0.01), edge-expansion (R = 0.53, p < 0.01), and outlying patches (R = 0.51, p < 0.01). Large patches were not significantly correlated with flood vulnerability (R = 0.18, p > 0.1), but there was a negative trend. Infilling patch growth was significantly associated with flood vulnerability over a long period (R = 0.27, p < 0.05). In addition, we suggest nature-based soft adaptations or village merging for small patches and outlying patches. Our findings have important scientific significance for adequately understanding the interplay between BLF growth and flood risk. It has practical implications for the formulation of integrated flood risk management strategy and the sustainable development of floodplains.

Source apportionment of PM2.5 was performed using positive matrix factorization (PMF) based on chemical composition data from 24-h filters collected throughout the year of 2015 at two sites in Macao (TG and PE), where TG is a general station and PE is near the city's ferry terminal. The input data sets include major inorganic ions, organic carbon and elemental carbon, elements and organic tracers (non-polar organic compounds and sugar compounds). Eight factors were resolved, namely, (1) secondary sulfate formation process, (2) secondary nitrate formation process, (3) biomass burning, (4) industrial emissions, (5) residual oil combustion, (6) sea salt, (7) dust, and (8) vehicle + helicopter emissions. Among the resolved sources, secondary sulfate and secondary nitrate were the major PM2.5 contributors, contributing to 33% and 23% of PM2.5 mass annually. Vehicle + helicopter emissions contributed to 12%, followed by industrial emissions (10%). Back trajectory analysis and conditional probability function (CPF) analysis were performed on the PMF-resolved factor contributions to distinguish the local and regional sources. Industrial emissions and vehicle + helicopter emissions showed different air mass impact at the two sites. The CPF plots confirmed the site differences in the resolved vehicle + helicopter emissions and industrial emissions were consistent with the geographical features of Macao and known local emission sources. The role of organic tracers was examined by comparing PMF runs with and without the inclusion of organics, denoted PMForg and PMFt, respectively. The results showed that the same set of contributing sources were resolved while noticeable differences of absolute PM2.5 contributions were observed between PMForg and PMFt and lower mass closure was noted for PMFt. PMF runs without source-indicative organic tracers tend to produce higher estimations of source contributions from biomass burning and vehicle exhaust factors than that with the organics while underestimate secondary nitrate, industrial emissions, and dust. This work highlights the importance of organic tracers in achieving more accurate source apportionment.

Phosphatidylinositol 3-kinase alpha (PI3Kα) is among the most important PI3K isoforms and has been associated with multiple human cancers. Therefore, PI3Kα has garnered considerable attention as a viable target for anticancer drug discovery, and thus the identification and development of highly potent inhibitors of this isoform has become an important line of research. Here, structure-based virtual screening, bioassays, and molecular dynamics simulations were performed to discover novel potential PI3Kα inhibitors. TCM-N1 (ZINC13382850) was identified as a possible PI3Kα inhibitor. Particularly, fluorescence quenching assays determined that the binding affinity of the aforementioned compound was superior to that of a reference ligand (BYL719; i.e. a known PI3Kα inhibitor). Moreover, enzymatic activity and cell proliferation inhibition assays indicated that TCM-N1 possessed a moderate inhibition activity against PI3Kα and a relatively high anti-tumor proliferation ability in gastric, colorectal, and cervical cancer cells. The binding model and related thermodynamic parameters further demonstrated that TCM-N1 was tightly embedded into the ATP-binding pocket via hydrogen bonds, van der Waals interactions, and hydrophobic interactions. Therefore, this study provides promising insights into the development and design of more potent PI3Kα-inhibiting analogs. Communicated by Ramaswamy H. Sarma.

Our previous study demonstrated that the mammalian target of rapamycin complex 1 (mTORC1) pathway is activated in peritoneal fibrosis under high glucose condition. This study aimed to investigate whether valsartan inhibits high glucose-induced peritoneal fibrosis via decreasing the activity of the mTORC1 pathway. We used high glucose peritoneal dialysis solution in a mouse peritoneal dialysis model to induce peritoneal fibrosis in vivo and high glucose in human peritoneal mesothelial cells (HPMCs) to stimulate extracellular matrix accumulation in vitro. After injections of peritoneal dialysis solution containing 4.25% glucose for four weeks, mice showed typical features of peritoneal fibrosis, including markedly increased peritoneal thickness, excessive matrix deposition, increased peritoneal permeability, and higher expression of extracellular matrix proteins, such as α-smooth muscle actin (α-SMA) and collagen I. Oral gavage of valsartan significantly ameliorated these pathological changes at both week 6 and week 8. These effects of valsartan were closely correlated with a decrease in the activation of the mTORC1 signal, which was mediated by the downregulation of the protein expression of phosphorylated (p)-mTOR, p-eukaryotic initiation factor 4E-binding protein 1, and p-p70 S6 kinase 1. Further research showed that the protein expression of mTORC1 signal was positively correlated with the expression of both α-SMA and collagen I in the peritoneum. In vitro, high glucose increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly inhibited high glucose-induced extracellular matrix accumulation in HPMCs. The effect was also accompanied by a decrease in the activation of the mTORC1 signal. Furthermore, the mTOR agonist MHY1485 reversed the downregulation of extracellular matrix components in HPMCs, even in the presence of valsartan. We conclude that valsartan exerts a protective effect against high glucose-induced peritoneal fibrosis via suppressing the activity of the mTORC1 pathway.Impact statementOur study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. In vitro, HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan in vivo and in vitro. Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I in vitro, even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.

In order to reduce switching loss of neutral-point clamped (NPC) three-level inverter (TLI), a switching loss minimized discontinuous PWM (SLMDPWM) strategy is proposed firstly. There are DC offset and AC ripple on the neutral-point (NP) voltage when SLMDPWM is used, which causes an appearance of low frequency harmonics (LFHs) in the output voltage. Aiming at this drawback, reduced LFHs (RLFHs) method is then proposed. While using RLFHs, the self-equilibrium ability of NP voltage is thus lost. So, active neutral-point voltage control (ANPVC) is also proposed. The performances of NPC TLI with the proposed DPWM and other DPWMs are compared by simulation and experimental results. The results show that switching loss, LFHs can be reduced significantly and the NP voltage can be controlled within an allowable range. Therefore, the multiple control objectives of reduced switching loss, no LFHs and allowable NP voltage are achieved.

OBJECTIVE: To explore the efficacy and safety of intravenous injection of tranexamic acid (TXA) combined with local use of TXA cocktail in intertrochanteric fracture fixation with proximal femoral nail antirotation (PFNA). METHODS: Patients with intertrochanteric fractures who underwent close reduction and internal fixation with PFNA between February 2018 and March 2019 were enrolled in the study. Among them, 45 patients who met the selection criteria were included in the study and randomly allocated into 3 groups (n=15). The patients in group A were not received TXA during perioperative period. The patients were intravenously injected of 1.0 g TXA before operation in group B and combined with local use of TXA cocktail during operation in group C. There was no significant difference in the age, gender, body mass index, fracture classification, disease duration, and complications between groups (P>0.05). The perioperative blood loss and blood transfusion rate, the visual analogue scale (VAS) score before operation and at 12, 24, and 48 hours after operation, the levels of prostaglandin E2 (PGE2) and bradykinin (BK) before operation and at 1 and 3 days after operation, postoperative complications, and the maximum amplitude (MA) of thromboelastogram were recorded and compared between groups. RESULTS: The total blood loss, hidden blood loss, and visible blood loss were significantly lower in groups B and C than those in group A (P0.05). The postoperative VAS scores and the levels of PGE2 and BK were significantly lower in group C than in groups A and B (P0.05). The incidences of postoperative complications were 33.33% (5/15), 20.00% (3/15), and 13.33% (2/15) in groups A, B, and C, respectively, with no significant difference between groups (χ(2)=1.721, P=0.550). CONCLUSION: For intertrochanteric fractures, application of intravenous injection of TXA combined with local use of TXA cocktail in PFNA fixation can reduce perioperative blood loss, relieve pain after operation, and do not increase the risk of complications.

WRINKLED1 (WRI1), an APETALA2/ethylene-responsive-element-binding protein (AP2/EREBP) subfamily transcription factor, plays a crucial role in the transcriptional regulation of plant fatty acid biosynthesis. In this study, GmWRI1a was overexpressed in the soybean cultivar ‘Dongnong 50’ using Agrobacterium-mediated transformation to generate three transgenic lines with high seed oil contents. PCR and Southern blotting analysis showed that the T-DNA was inserted into the genome at precise insertion sites and was stably inherited by the progeny. Expression analysis using qRT-PCR and Western blotting indicated that GmWRI1a and bar driven by the CaMV 35S promoter were significantly upregulated in the transgenic plants at different developmental stages. Transcriptome sequencing results showed there were obvious differences in gene expression between transgenic line and transgenic receptor during seed developmental stages. KEGG analysis found that the differentially expressed genes mainly annotated to metabolic pathways, such as carbohydrated metabolism and lipid metabolism. A 2-year single-location field trial revealed that three transgenic lines overexpressing GmWRI1a (GmWRI1a-OE) showed a stable increase in seed oil content of 4.97–10.35%. Importantly, no significant effect on protein content and yield was observed. Overexpression of GmWRI1a changed the fatty acid composition by increasing the linoleic acid (C18:2) content and decreasing the palmitic acid (C16:0) content in the seed. The three GmWRI1a-OE lines showed no significant changes in agronomic traits. The results demonstrated that the three GmWRI1a overexpression lines exhibited consistent increases in seed oil content compared with that of the wild type and did not significantly affect the seed yield and agronomic traits. The genetic engineering of GmWRI1a will be an effective strategy for the improvement of seed oil content and value in soybean.

Diabetic kidney disease (DKD) is a microvascular complication of type 2 diabetes. The study of DKD mechanisms is the most important target for the prevention of DKD. Renal senescence is one of the important pathogeneses for DKD, but the mechanism of renal and cellular senescence is unclear. Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD. This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs) induced by high glucose. HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640) in vitro. The effect of high glucose on morphology of HGMCs was observed 72 h after intervention. The cell cycle was examined by flow cytometry. The telomere length was measured by Southern blotting. The expression levels of p53, p21 and Rb proteins in p53-p21-Rb signaling pathway and p-stat1, p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively. The expression of miR-126 was examined by qRT-PCR. MiR-126 mimics was transfected into HGMCs. The effects of miR-126 mimics transfection on cell morphology, cell cycle, telomere length, p53, p21, Rb, p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1 phase but also shortened the telomere length. High glucose led to high expression of p53, p21, Rb, p-stat1 and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways. Moreover, the miR-126 was decreased in HGMCs induced by high glucose. It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs. The results may serve as a new strategy for the treatment of DKD.

Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA. In this study, we propose a new strategy by the combination of micelles disassembly and separated polycations charge reversal. FPBA (3-fluoro-4-carboxyphenylboronic acid) grafted PEI 1.8 k (polyethylenimine) as the polycations of PEI-FPBA and dopamine (with diol-containing moiety) conjugated with cholesterol as the hydrophobic part (Chol-Dopa). The PFCDM micelles was assembled by PEI-FPBA and Chol-Dopa, based on the FPBA-Dopa conjugation. The prepared PFCDM showed strong siRNA loading ability and superior stability in the presence of PBS or serum. Besides, the PFCDM exhibited excellent ATP sensibility. The intracellular ATP could effectively trigger the disassembly of micelles and charge reversal of PEI-FPBA, resulting in the burst release of siRNA in the cytosol. With the property of extracellular stability and intracellular instability, PFCDM displayed good performance on in vitro and in vivo luciferase silencing on 4T1 cells. It should also be noted that the assembly of low molecular weight PEI was relatively safe to cells compared with 25 k PEI. To sum up, the ATP-fueled assembly and charge reversible micelles gave examples for polyplexes to achieve better stability and on demand cargo release at the same time and shows potential to be used for in vitro and in vivo siRNA transfection.

Cationic polyplex as commonly used nucleic acid carriers faced several shortcomings, such as high cytotoxicity, low serum stability, and slow cargo release at the target site. The traditional solution is covering a negative charged layer (e.g., hyaluronic acid, HA) via electrostatic interaction. However, it was far from satisfactory for the deshielding by physiological anions in circulation (e.g., serum proteins, phosphate). In this study, we proposed a new strategy of reversible covalent cross-linking to enhance stability in circulation and enable stimuli-disassembly of polyplexes in tumor cells. Here, 25k polyethylenimine (PEI) was chosen as model polycations for veriying the hypothesis. HA-PEI conjugation was formed by the cross-linking of adenosine triphosphate grafted HA (HA-ATP) with phenylboronic acid grafted PEI (PEI-PBA) via the chemical reaction between PBA and ATP. Compared with noncovalent polyplex by electrostatic interaction (HA/PEI), HA-PEI exhibited much better colloidal stability and serum stability. The covered HA-ATP layer on PEI-PBA could maintain stable in the absence of physiological anions, while HA layer on PEI in HA/PEI group showed obvious detachment after anion's competition. More importantly, the covalent cross-linking polyplex could selectively release siRNA in the ATP rich environment of cytosol and significantly improve siRNA silence. Besides, the covalent cross-linking with HA-ATP could effectively reduce the cytotoxicity of cationic polyplex, improve the uptake by B61F10 cells and promote the endosomal escape. Consequently, this strategy of HA-PEI conjugation significantly enhanced the siRNA transfection in the absence or presence of FBS (fetal bovine serum) on B16F10 cells and CHO cells. Taken together, the reversible covalent cross-linking approach shows obvious superiority compared with the noncovalent absorption strategy. It held great potential to be developed to polish up the performance of cationic polyplex on reducing the toxicity, enhancing the serum tolerance and achieving controlled release of siRNA at target site.

Hierarchical three dimensional MoS2nanostructures composed of small sheet-like nanostructures are successfully prepared using a simple two-step hydrothermal process with sodium dodecyl sulfate (SDS), as a surface modifier. The as-preparedMoS2nanospheres are characterized by XRD, BET, XPS, EDS, SEM and HRTEM. The gas–sensing properties of as–prepared MoS2nanostructures are tested at 175–230 °C temperatures for 50–500 ppm concentration range, using an efficient ceramic-tube sensor system via an intelligent gas testing system. A high response and selectivity towards carbon monoxide than other gases is observed. Comparative studies of MoS2nanostructures for different concentration of carbon monoxide gas and definite sensor-stability for different gases are studied, as well. The sensor fabrication and sensing mechanism is discussed as well.

Background Focal segmental glomerulosclerosis (FSGS) is often accompanied with tubulointerstitial lesion. This study aimed to assess the role of urinary biomarkers in predicting tubulointerstitial lesion and treatment response in FSGS patients. Methods Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β- d -glucosaminidase (NAG) and retinol-binding protein (RBP) were measured in 32 FSGS patients and 22 patients with minimal change nephrotic syndrome. Patients with FSGS were followed up to investigate the value of these markers in predicting treatment response. Results FSGS patients had higher urinary NGAL, NAG and RBP than patients with minimal change nephrotic syndrome with comparable proteinuria. A cutoff value of 15.87 ng/mL NGAL demonstrated 87.1% sensitivity and 59.1% specificity for the diagnosis of FSGS, with an area under the receiver operator characteristic curve of 0.801. In FSGS, these markers correlated significantly with the degree of acute tubulointerstitial damage but not with chronic tubulointerstitial lesion. Response to immunosuppressive therapy was significantly different in patients with KIM-1, NAG and RBP levels below and above the cutoff values. Conclusions Urinary NGAL, KIM-1, NAG and RBP are reliable biomarkers of tubulointerstitial lesion in FSGS patients. The measurements of these markers may be useful in diagnosing FSGS, detecting acute tubulointerstitial lesion and predicting treatment response.

Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients. Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D

Aim Catheter malfunction is the main reason for early peritoneal dialysis (PD) technique failure. This study aimed to evaluate the effect of a new surgery technique with catheter fixation to the lower abdominal wall combined with straight upward tunnel and low implant position in reducing catheter malfunction. Methods Patients with end stage renal disease who received PD in our centre from January 2013 to December 2015 were involved in this study. They were randomly divided into three groups according to surgical technique: traditional open surgery group, modified open surgery group and modified open surgery with catheter fixation group. All patients were followed up for six months after surgery. Catheter- related complications were analyzed. Results A total of 152 patients were involved. Among them, 49 received traditional open surgery (TOS group), 49 received modified open surgery (MOS group), and 54 received modified open surgery with catheter fixation (MOS-F group). During follow-up, no patients (0%) in MOS-F group developed catheter malfunction which was significantly lower than that of the TOS group (0 vs 16.33%, P = 0.002). Although not statistically significant, the incidence of catheter malfunction was lower in MOS-F group than that in MOS group (0 vs 4.08%, P = 0.134). No significant difference was observed in the episodes of infection, bleeding, leakage, inflow or outflow pain, hernia and delayed wound healing among the three groups (all P > 0.05). Conclusions Catheter fixation combined with straight upward tunnel and low implant position can effectively prevent catheter malfunction in PD catheter placement.

Peritoneal fibrosis (PF) is characterized by progressive extracellular matrix (ECM) accumulation. Increasing evidence has suggested that ECM synthesis was increased in human peritoneal mesothelial cells (HPMCs) under high-glucose conditions, but the effects of high-glucose peritoneal dialysis solution (PDS) on ECM synthesis have not been fully elucidated. The aim of this study was to explore the potential mechanisms of high-glucose PDS-induced production of ECM in HPMCs. HPMCs were stimulated by high-glucose PDS. The activity of mammalian target of rapamycin complex 1 (mTORC1) was inhibited by rapamycin or regulatory-associated protein of mTOR (raptor) siRNA. Morphological changes in the cells were observed under an inverted microscope. Oil red O, filipin staining and high-performance liquid chromatography were used to examine lipid accumulation. The expression of low-density lipoprotein receptor (LDLr) regulation, the mTORC1 pathway and ECM-associated markers were assessed by real-time polymerase chain reaction and western blot analysis. The results showed that after treatment with PDS, HPMCs showed notable elongation consistent with the morphology of myofibroblasts, and the expression of ECM proteins such as α-smooth muscle actin, fibroblast specific protein-1 and collagen I was increased. In addition, there was a parallel increase in the ECM and lipid accumulation. Moreover, the effect of intracellular lipid deposition was closely correlated with the dysregulation of LDLr, which was mediated through the upregulation of LDLr, sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), and SREBP-2 and through the enhanced coexpression of the SCAP with the Golgin. Further analysis showed that PDS enhanced the protein phosphorylation of mTOR, eukaryotic initiation factor 4E-binding protein 1, and p70 S6 kinase. Interestingly, blocking mTORC1 activity reversed the dysregulation of LDLr, even in the presence of PDS. These effects were also accompanied by a decrease in the expression of ECM components. Our findings demonstrated that increased mTORC1 activity exacerbated ECM formation in HPMCs by disrupting LDLr regulation, which contributed to lipid disorder-mediated PF.