GPX7 reduces chondrocyte inflammation and extracellular matrix degradation triggered by IL­1ß, via a mechanism mediated by ferroptosis.

During osteoarthritis (OA), chondrocytes become highly active, with increased matrix synthesis and inflammatory cytokine­induced catabolic pathways. Early intervention strategies targeting pathological changes may attenuate or halt disease progression. The present study aimed to reveal the role of glutathione peroxidase (GPX)7 in OA. For this purpose, a research model was established by inducing C28/I2 human chondrocytes with interleukin (IL)­1ß, and the expression level of GPX7 was determined. To explore its roles, C28/I2 cells were transfected to gain GPX7 overexpression. The effects of GPX7 overexpression on intracellular inflammation, extracellular matrix (ECM) degradation, apoptosis and ferroptosis were then evaluated. In addition, the cells were treated with the ferroptosis inducer, erastin, and its effects on the aforementioned phenotypes were assessed. The level of GPX7 was decreased in response to IL­1ß treatment, and GPX7 overexpression suppressed cellular inflammation, ECM degradation and apoptosis. Moreover, the reduction of lipid peroxidation, ferrous ions and transferrin indicated that GPX7 overexpression inhibited ferroptosis. Subsequently, inflammation, ECM degradation and apoptosis were found to be promoted in the cells upon treatment with erastin. These findings suggested that the regulatory role of GPX7 may be mediated by a pathway involving ferroptosis. On the whole, the present study revealed that GPX7 reduces IL­1ß­induced chondrocyte inflammation, apoptosis and ECM degradation partially through a mechanism involving ferroptosis. The results of the present study lay a theoretical foundation for subsequent OA­related research and may enable the development of translational strategies for the treatment of OA.

Correlation between axial symptoms and cervical sagittal alignment parameters in patients with two-level or three-level cervical spondylotic myelopathy: anterior cervcial discectomy and fusion versus hybird surgery.

OBJECTIVE: To comparatively analyze the correlation between axial symptoms (AS) and cervical sagittal alignment parameters after anterior cervical discectomy and fusion (ACDF) and hybrid surgery (HS). METHODS: From January 2018 to June 2023, 74 patients who underwent ACDF (n = 36) or HS (n = 38) for two-level or three-level cervical spondylotic myelopathy were retrospectively analyzed. The Visual Analogue Scale (VAS), Japanese Orthopedic Association (JOA), Neck Disability Index (NDI) were recorded to assess clinical outcomes. Cervical sagittal alignment parameters (Cobb's angle C2-7, C7 slope [C7S], and C2-7 sagittal vertical axis [C2-7 SVA]) were measured preoperatively, 3 days postoperatively, and at the last follow-up. The range of motion (ROM) of C2-7 and ROM of surgical segment were measured. The occurrence of AS was observed at the last follow-up. Logistic regression was used to analyze the correlation between postoperative AS and cervical sagittal alignment parameters. RESULTS: Both in ACDF group and HS group, VAS, JOA and NDI scores showed significant improvements at 3-day postoperation and at the last follow-up (P < 0.05). However, there was no significant difference between the two groups (P > 0.05). The Cobb's angle C2-7 and C7S were significantly increased at 3 days postoperation compared with pre-operatively in both groups (P < 0.05). C2-7SVA was increased in both groups 3 days after surgery compared with pre-operatively, but there was no significant difference (P > 0.05). At the last follow-up, the ROM of C2-7 in ACDF group was significantly smaller than HS group (P < 0.05). The prevalence of postoperative AS in the ACDF group and HS group was 41.7 and 18.4%, respectively, with statistical difference between the two groups (P < 0.05). When simple Logistic regression analysis was used, the last Cobb's angle C2-7 (ß = -0.088), the last C2-7SVA (ß = 0.099) in ACDF group and the last C2-7SVA (ß = 0.222) in HS group were all correlated with the occurrence of postoperative AS. When multiple Logistic regression analysis was used, only the last C2-7SVA (ß = 0.181) in the HS group was positively correlated with the occurrence of postoperative AS. CONCLUSIONS: Both ACDF and HS can achieve satisfied clinical outcomes. ACDF and HS can improve cervical sagittal balance to a certain extent, and HS is superior to ACDF in maintaining ROM. The decrease of the last Cobb's angle C2-7 and the increase of the last C2-7SVA may be related to the occurrence of AS after ACDF. The increase of the last C2-7SVA was an independent risk factor for the occurrence of AS after HS.

New evidence on the controversy over the correlation between vertebral osteoporosis and intervertebral disc degeneration: a systematic review of relevant animal studies.

OBJECTIVE: The effect of vertebral osteoporosis on disc degeneration remains controversial. The aim of this study was to conduct a systematic review and meta-analysis of relevant animal studies to shed more light on the effects and mechanisms of vertebral osteoporosis on disc degeneration and to promote the resolution of the controversy. METHODS: The PubMed, Cochrane Library, and Embase databases were searched for studies that met the inclusion criteria. Basic information and data were extracted from the included studies and data were analyzed using STATA 15.1 software. This study was registered on INPLASY with the registration number INPLASY202370099 and https://doi.org/10.37766/inplasy2023.7.0099 . RESULTS: A total of 13 studies were included in our study. Both animals, rats and mice, were covered. Meta-analysis results showed in disc height index (DHI) (P < 0.001), histological score (P < 0.001), number of osteoblasts in the endplate (P = 0.043), number of osteoclasts in the endplate (P < 0.001), type I collagen (P < 0.001), type II collagen (P < 0.001), aggrecan (P < 0.001), recombinant a disintegrin and metalloproteinase with thrombospondin-4 (ADAMTS-4) (P < 0.001), matrix metalloproteinase-1 (MMP-1) (P < 0.001), MMP-3 (P < 0.001), MMP-13 (P < 0.001), the difference between the osteoporosis group and the control group was statistically significant. In terms of disc volume, the difference between the osteoporosis group and the control group was not statistically significant (P = 0.459). CONCLUSION: Our study shows that vertebral osteoporosis may exacerbate disc degeneration. Abnormal bone remodeling caused by vertebral osteoporosis disrupts the structural integrity of the endplate, leading to impaired nutrient supply to the disc, increased expression of catabolic factors, and decreased levels of type II collagen and aggrecan may be one of the potential mechanisms.

Timing of decompression in central cord syndrome: a systematic review and meta-analysis.

PURPOSE: This study compared the recovery of motor function and the safety of early and delayed surgical intervention in patients with central cord syndrome (CCS). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were employed to retrieve the targeted studies published from inception to February 19, 2023. Comparative studies of early versus delayed surgical decompression in CCS based on American Spinal Injury Association motor score (AMS) recovery, complication rates, and mortality were selected. The statistical analyses were performed using STATA 16.0 and RevMan 5.4. RESULTS: Our meta-analysis included 13 studies comprising 8424 patients. Results revealed that early surgery improved AMS scores significantly compared with delayed surgery, with an increase in MDs by 7.22 points (95% CI 1.98-12.45; P = 0.007). Additionally, early surgery reduced the complication rates than delayed surgery (OR 0.53, 95% CI 0.42-0.67, P < 0.00001). However, no significant difference was observed in mortality between the two groups (OR 0.97; 95% CI 0.75-1.26; P = 0.84). CONCLUSIONS: Early surgical decompression for CCS can improve motor function and reduce the incidence of complications without affecting the mortality rate in patients. Future research should focus on investigating and analyzing the optimal window period for early CCS surgery. Additionally, the timing of surgery should be determined based on the patient's condition and available medical resources.

Metabolomic insight into regulatory mechanism of heterotrophic bacteria nitrification-aerobic denitrification bacteria to high-strength ammonium wastewater treatment.

This work aimed to elucidate the metabolic mechanism of heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria influenced by varying concentrations of ammonium nitrogen (NH4+-N) in high-strength synthetic wastewater treatment. The results showed that the removal rates of NH4+-N and total nitrogen, along with enzymatic activities related to nitrification and denitrification, increased with rising NH4+-N concentrations (N500:500 mg/L, N1000:1000 mg/L and N2000:2000 mg/L). The relative abundances of HN-AD bacteria were 50 %, 62 % and 82 % in the three groups. In the N2000 group, the cAMP signaling pathway, glycerophospholipid metabolites, purines and pyrimidines related to DNA/RNA synthesis, electron donor NAD+-related energy, the tricarboxylic acid (TCA) cycle and glutamate metabolism were upregulated. Therefore, influent NH4+-N at 2000 mg/L promoted glutamate metabolism to accelerate the TCA cycle, and enhanced cellular energy and advanced denitrification activity of bacteria for HN-AD. This mechanism, in turn, enhanced microbial growth and the carbon and nitrogen metabolism of bacteria for HN-AD.

LncRNA MIR22HG/microRNA-9-3p/IGF1 in nonalcoholic steatohepatitis, the ceRNA network increases fibrosis by inhibiting autophagy and promoting pyroptosis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is known to progress due to the impact of long non-coding RNAs (lncRNAs), which have been linked to autophagy, pyroptosis, and fibrosis in NASH cells. However, the exact mechanisms underpinning these processes remain unclear. This study focuses on the role of lncRNA MIR22HG (MIR22HG) in NASH. METHODS: The expression of differentially expressed lncRNA was analyzed by RNA sequencing. Mouse models of NASH induced by MCD and HFD were validated. The expression of MIR22HG in HFD and MCD mouse liver tissue samples, FFA cells constructed with HepG2 and Huh7, and human liver tissue samples were detected by QRT-PCR. In addition, We used RNA immunoprecipitation, luciferase reporting, miRNA transfection, plasmid construction, immunofluorescence, Western blot, qRT-PCR, ELISA, and hybridization techniques to elucidate the relationship between MIR22HG, microRNA-9-3p (miR-9-3p), and IGF1. In addition, the mechanism of MIR22HG and PTEN/AKT was explored by Western blot analysis. RESULTS: RNA-seq found that 3751 mRNAs and 23 lncRNAs were differentially expressed, which constituted a lncRNA-miRNA-mRNA regulatory network. Studies demonstrated the downregulation of MIR22HG in HFD and MCD mouse liver tissue samples (p = 1.00E-04 and p = 4.6E-03). Our results showed that overexpression of MIR22HG promoted autophagy and inhibited pyroptosis and fibrosis through the miR-9-3p/IGF1 pathway, thus slowing the occurrence and development of NASH. Further, we observed a low expression of MIR22HG and IGF1, but a high expression of miR-9-3p in NASH patients, a finding in alignment with our in vivo and in vitro results. CONCLUSION: Using MIR22HG as a biomarker and therapeutic target for NASH patients, we found that it plays a pivotal role in detecting autophagy, pyroptosis, and fibrosis through the ceRNA pathway.

Effect of caspase-1 (CASP1) combined with multimodal ultrasound features on the prognosis of breast cancer patients.

Background: Breast cancer (BRCA) is the malignant tumor with the highest incidence rate among women in the world, and its mortality rate ranks second. The purpose of our study is to explore the correlation between caspase-1 (CASP1) and the prognosis of BRCA patients and the potential mechanism of action, and to analyze the clinical value of CASP1 combined with multimodal ultrasound features in early screening and prognosis of BRCA. Methods: We analyzed The Cancer Genome Atlas (TCGA) database to confirm that CASP1 was expressed in BRCA patients and determine whether its expression was correlated with patient prognosis. The relationship between CASP1 expression and survival was measured by the clinicopathological parameters. Multivariate analysis was performed using Cox regression, and a nomogram was developed using these results for quality assurance purposes. The correlations between CASP1 and immune cells were investigated using the Tumor Immune Estimation Resource (TIMER) and TCGA databases. Next, we performed gene set enrichment analysis (GSEA) to determine the potential mechanism of action. Finally, to analyze the effect of CASP1 combined with multimodal ultrasonography characteristics on the prognosis of BRCA patients was studied by analyzing the clinical data of patients. Results: CASP1 expression was lower in BRCA tumor tissues than in the surrounding tissues. Patients with high CASP1 expression had better overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) than those with low CASP1 expression. GSEA suggested that CASP1 may affect the cell cycle, immune environment, inflammation, apoptosis, the HIPPOMERLIN pathway, Natural killer (NK) cell regulation of cytotoxicity, p53 expression, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, the mitogen-activated protein kinase (MAPK) pathway, extracellular matrix, etc., thereby influencing the biological events in BRCA. Among conventional ultrasound features and contrast-enhanced ultrasound (CEUS) features, mass margin status and blood flow grade were associated with the expression of CASP1. Meanwhile, patients with poor ultrasound features tended to have low CASP1 expression. Conclusions: CASP1 may be a novel predictive marker for BRCA patients. CASP1 combined with multimodal ultrasound features has good clinical value in the early screening and prognostic prediction of BRCA.

Does vertebral osteoporosis delay or accelerate lumbar disc degeneration? A systematic review.

The effect of vertebral osteoporosis on disc degeneration is still debated. The purpose of this study was to provide a systematic review of studies in this area to further reveal the relationship between the two. Relevant studies were searched in electronic databases, and studies were screened according to inclusion and exclusion criteria, and finally, basic information of the included studies was extracted and summarized. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 34 publications spanning 24 years were included in our study. There were 19 clinical studies, including 12 prospective studies and 7 retrospective studies. Of these, 7 considered vertebral osteoporosis to be positively correlated with disc degeneration, 8 considered them to be negatively correlated, and 4 considered them to be uncorrelated. Two cadaveric studies were included, one considered the two to be negatively correlated and one considered them not to be correlated. Seven animal studies were included, of which five considered a positive correlation between vertebral osteoporosis and disc degeneration and two considered a negative correlation between the two. There were also 6 studies that used anti-osteoporosis drugs for intervention, all of them were animal studies. Five of them concluded that vertebral osteoporosis was positively associated with disc degeneration, and the remaining one concluded that there was no correlation between the two. Our systematic review shows that the majority of studies currently consider an association between vertebral osteoporosis and disc degeneration, but there is still a huge disagreement whether this association is positive or negative. Differences in observation time and follow-up time may be one of the reasons for the disagreement. A large number of clinical and basic studies are still needed in the future to further explore the relationship between the two.

Artificial Intelligence-based Efficacy Prediction of Phase 3 Clinical Trial for Repurposing Heart Failure Therapies.

Introduction: Drug repurposing involves finding new therapeutic uses for already approved drugs, which can save costs as their pharmacokinetics and pharmacodynamics are already known. Predicting efficacy based on clinical endpoints is valuable for designing phase 3 trials and making Go/No-Go decisions, given the potential for confounding effects in phase 2. Objectives: This study aims to predict the efficacy of the repurposed Heart Failure (HF) drugs for the Phase 3 Clinical Trial. Methods: Our study presents a comprehensive framework for predicting drug efficacy in phase 3 trials, which combines drug-target prediction using biomedical knowledgebases with statistical analysis of real-world data. We developed a novel drug-target prediction model that uses low-dimensional representations of drug chemical structures and gene sequences, and biomedical knowledgebase. Furthermore, we conducted statistical analyses of electronic health records to assess the effectiveness of repurposed drugs in relation to clinical measurements (e.g., NT-proBNP). Results: We identified 24 repurposed drugs (9 with a positive effect and 15 with a non-positive) for heart failure from 266 phase 3 clinical trials. We used 25 genes related to heart failure for drug-target prediction, as well as electronic health records (EHR) from the Mayo Clinic for screening, which contained over 58,000 heart failure patients treated with various drugs and categorized by heart failure subtypes. Our proposed drug-target predictive model performed exceptionally well in all seven tests in the BETA benchmark compared to the six cutting-edge baseline methods (i.e., best performed in 266 out of 404 tasks). For the overall prediction of the 24 drugs, our model achieved an AUCROC of 82.59% and PRAUC (average precision) of 73.39%. Conclusion: The study demonstrated exceptional results in predicting the efficacy of repurposed drugs for phase 3 clinical trials, highlighting the potential of this method to facilitate computational drug repurposing.

Impact of age on short-term outcomes after pancreaticoduodenectomy: A retrospective case-control study of 260 patients.

Background: Although the increase of perioperative complications in the elderly undergoing pancreaticoduodenectomy (PD) surgery has been recognized, the definition of the "old patient" of PD in the studies is different and there is no accepted cut-off value at present. Methods: 279 consecutive patients who have undergone PD in our center between January 2012 and May 2020 were analyzed. Demographic features, clinical-pathological data and short-term outcomes were collected. The patients were divided into two groups, and the cut-off value (62.5 years) is picked based on the highest Youden Index. Primary endpoints were perioperative morbidity and mortality, and complications were classified according to the Clavien-Dindo Score. Results: A total of 260 patients with PD were included in this study. Postoperative pathology confirmed pancreatic tumors in 62 patients, bile duct tumor in 105, duodenal tumor in 90, and others in 3. Age (OR = 1.09, P < 0.01), and albumin (OR = 0.34, P < 0.05) were significantly correlated with postoperative Clavien-Dindo Score ≥3b. There were 173 (66.5%) patients in the younger group (<62.5 years) and 87 (33.5%) in the elderly group (≥62.5 years). Significant difference between two groups was demonstrated for Clavien-Dindo Score ≥3b (P < 0.01), postoperative pancreatic fistula (P < 0.05), and perioperative deceases (P < 0.05). Conclusions: Age and albumin were significantly correlated with postoperative Clavien-Dindo Score ≥3b, and there was no significant difference in predicting the grade of Clavien-Dindo Score. The cut-off value of elderly patients with PD was 62.5 years old and there were useful in predicting Clavien-Dindo Score ≥3b, pancreatic fistula, and perioperative death.

The visceral pancreatic neck anterior distance may be an effective parameter to predict post-pancreaticoduodenectomy clinically relevant postoperative pancreatic fistula.

Background: The clinically relevant postoperative pancreatic fistula (CR-POPF) is significantly correlated with a high post-pancreaticoduodenectomy (PD) mortality rate. Several studies have reported an association between visceral obesity and CR-POPF. Nevertheless, there are many technical difficulties and controversies in the measurement of visceral fat. The aim of this research was to determine whether the visceral pancreatic neck anterior distance (V-PNAD) was a credible predictor for CR-POPF. Methods: We retrospectively analyzed the data of 216 patients who underwent PD in our center between January 2016 and August 2021. The correlation of patients' demographic information, imaging variables, and intraoperative data with CR-POPF was assessed. Furthermore, areas under the receiver operating characteristic curves for six distances (abdominal thickness, visceral thickness, abdominal width, visceral width, abdominal PNAD, V-PNAD) were used to identify the best imaging distance to predict POPF. Results: In the multivariate logistic analysis, V-PNAD (P < 0.01) was the most significant risk factor for CR-POPF after PD. Males with a V-PNAD >3.97 cm or females with a V-PNAD >3.66 cm were included into the high-risk group. The high-risk group had a higher prevalence of CR-POPF (6.5% vs. 45.1%, P < 0.001), intraperitoneal infection (1.9% vs. 23.9%, P < 0.001), pulmonary infection (3.7% vs. 14.1%, P = 0.012), pleural effusion (17.8% vs. 33.8%, P = 0.014), and ascites (22.4% vs. 40.8%, P = 0.009) than the low-risk group. Conclusion: Of all imaging distances, V-PNAD may be the most effective predictor of CR-POPF. Moreover, high-risk patients (males, V-PNAD >3.97 cm; females, V-PNAD >3.66 cm) have a high incidence of CR-POPF and poor short-term post-PD prognosis. Therefore, surgeons should perform PD carefully and take adequate preventive measures to reduce the incidence of pancreatic fistula when the patient has a high V-PNAD.

Efficient recycling of silicon cutting waste for producing high-quality Si-Fe alloys.

A tremendous amount of silicon cutting waste (SCW) is being produced during slicing Si ingots, which leads to a great waste of resources and serious environmental pollution. In this study, a novel method that recycling SCW to produce Si-Fe alloys was proposed, which not only provides a process with low energy consumption, low cost, and short flow for producing high-quality Si-Fe alloys but also achieves a more effective recycling of SCW. The optimal experimental condition is investigated to be a smelting temperature of 1800 °C and a holding time of 10 min. Under this condition, the yield of Si-Fe alloys and the Si recovery ratio of SCW were 88.63% and 87.81%, respectively. Compared with the present industrial recycling method that uses SCW to prepare metallurgy-grade Si ingot by an induction smelting process, this Si-Fe alloying method can achieve a higher Si recovery ratio of SCW at a shorter smelting time. The promoting mechanism of Si recovery by Si-Fe alloying is mainly expressed as follows: (1) facilitating the separation of Si from SiO2-based slag; (2) reducing the oxidization and carbonization loss of Si by accelerating the heating of raw materials and reducing the exposed area of Si.

Arg/Lys-containing IDRs are cryptic binding domains for ATP and nucleic acids that interplay to modulate LLPS.

Most membrane-less organelles (MLOs) formed by LLPS contain both nucleic acids and IDR-rich proteins. Currently while IDRs are well-recognized to drive LLPS, nucleic acids are thought to exert non-specific electrostatic/salt effects. TDP-43 functions by binding RNA/ssDNA and its LLPS was characterized without nucleic acids to be driven mainly by PLD-oligomerization, which may further transit into aggregation characteristic of various neurodegenerative diseases. Here by NMR, we discovered unexpectedly for TDP-43 PLD: 1) ssDNAs drive and then dissolve LLPS by multivalently and specifically binding Arg/Lys. 2) LLPS is driven by nucleic-acid-binding coupled with PLD-oligomerization. 3) ATP and nucleic acids universally interplay in modulating LLPS by competing for binding Arg/Lys. However, the unique hydrophobic region within PLD renders LLPS to exaggerate into aggregation. The study not only unveils the first residue-resolution mechanism of the nucleic-acid-driven LLPS of TDP-43 PLD, but also decodes a general principle that not just TDP-43 PLD, all Arg/Lys-containing IDRs are cryptic nucleic-acid-binding domains that may phase separate upon binding nucleic acids. Strikingly, ATP shares a common mechanism with nucleic acids in binding IDRs, thus emerging as a universal mediator for interactions between IDRs and nucleic acids, which may underlie previously-unrecognized roles of ATP at mM in physiology and pathology.

Understanding gilteritinib resistance to FLT3-F691L mutation through an integrated computational strategy.

FMS-like tyrosine kinase 3 (FLT3) serves as an important drug target for acute myeloid leukemia (AML), and gene mutations of FLT3 have been closely associated with AML patients with an incidence rate of ~ 30%. However, the mechanism of the clinically relevant F691L gatekeeper mutation conferred resistance to the drug gilteritinib remained poorly understood. In this study, multiple microsecond molecular dynamics (MD) simulations, end-point free energy calculations, and dynamic correlated and network analyses were performed to investigate the molecular basis of gilteritinib resistance to the FLT3-F691L mutation. The simulations revealed that the resistant mutation largely induced the conformational changes of the activation loop (A-loop), the phosphate-binding loop, and the helix αC of the FLT3 protein. The binding abilities of the gilteritinib to the wild-type and the F691L mutant were different through the binding free energy prediction. The simulation results further indicated that the driving force to determine the binding affinity of gilteritinib was derived from the differences in the energy terms of electrostatic and van der Waals interactions. Moreover, the per-residue free energy decomposition suggested that the four residues (Phe803, Gly831, Leu832, and Ala833) located at the A-loop of FLT3 had a significant impact on the binding affinity of gilteritinib to the F691L mutant. This study may provide useful information for the design of novel FLT3 inhibitors specially targeting the F691L gatekeeper mutant.

Application of exosomes in the diagnosis and treatment of pancreatic diseases.

Pancreatic diseases, a serious threat to human health, have garnered considerable research interest, as they are associated with a high mortality rate. However, owing to the uncertain etiology and complex pathophysiology, the treatment of pancreatic diseases is a challenge for clinicians and researchers. Exosomes, carriers of intercellular communication signals, play an important role in the diagnosis and treatment of pancreatic diseases. Exosomes are involved in multiple stages of pancreatic disease development, including apoptosis, immune regulation, angiogenesis, cell migration, and cell proliferation. Thus, extensive alterations in the quantity and variety of exosomes may be indicative of abnormal biological behaviors of pancreatic cells. This phenomenon could be exploited for the development of exosomes as a new biomarker or target of new treatment strategies. Several studies have demonstrated the diagnostic and therapeutic effects of exosomes in cancer and inflammatory pancreatic diseases. Herein, we introduce the roles of exosomes in the diagnosis and treatment of pancreatic diseases and discuss directions for future research and perspectives of their applications.

Tamsulosin attenuates high glucose- induced injury in glomerular endothelial cells.

Diabetic nephropathy (DN) is a common complication of diabetes. Tamsulosin is a selective α1-AR antagonist. α1-AR is expressed widely in kidney tissues and has displayed its various physiological functions. However, whether Tamsulosin has affects DN is unknown. To our knowledge, this is the first time it has been examined whether Tamsulosin possesses a beneficial effect in high glucose-challenged glomerular endothelial cells (GECs). Firstly, we found that Tamsulosin reduced high glucose-induced expressions of TNF-α, IL-6, and IL-8. Secondly, Tamsulosin alleviated high glucose-induced expressions of MMP-2 and MMP-9. Thirdly, Tamsulosin inhibited the expressions of VCAM-1 and ICAM-1. Importantly, our results indicate that Tamsulosin inhibited high glucose-induced expressions of fibrosis factors such as Col-1 and TGF-ß1. Additionally, we found that Tamsulosin ameliorated oxidative stress via reducing the generation of ROS and preventing the activation of p38. Mechanistically, we found that Tamsulosin attenuated high glucose-induced activation of NF-κB. Based on these findings, we conclude that Tamsulosin could attenuate high glucose-induced injury in GECs through alleviating oxidative stress and inflammatory response.

Preparation of Al-Si alloys with silicon cutting waste from diamond wire sawing process.

Large amounts of silicon cutting waste (SCW) are generated during Si wafers producing process. In this paper, SCW was mixed with Al powder to prepare Al-Si alloys by a one-step smelting process in corundum crucibles. The influences of smelting temperature (1000 °C, 1200 °C and 1500 °C) on the products of each zone (surface layer zone, loose granular zone and blocky products zone) were investigated. Al-Si alloys in the form of granular and blocky were prepared and the blocky Al-Si alloys mainly concentrated in the blocky products zone. The increase of smelting temperature can promote the aggregation of Al-Si alloy particles. The yields of Al-Si alloy blocks obtained at 1000 °C, 1200 °C and 1500 °C were 0%, 58% and 69%, respectively. The Si contents of Al-Si alloy blocks at 1200 °C and 1500 °C were 15.8 wt% and 17.1 wt% respectively. After compacting the raw materials, the yields of the blocky Al-Si alloys obtained at 1000 °C, 1200 °C and 1500 °C were increased to 65%, 72% and 79% and the corresponding Si contents of the blocky Al-Si alloys were increased to 16.0 wt%, 16.5 wt% and 17.3 wt% respectively. The reaction mechanism of the alloying process was also investigated.

Achieving High Yield Strength and Ductility in As-Extruded Mg-0.5Sr Alloy by High Mn-Alloying.

The effect of Mn on the microstructure and mechanical properties of as-extruded Mg-0.5Sr alloy were discussed in this work. The results showed that high Mn alloying (2 wt.%) could significantly improve the mechanical properties of the alloys, namely, the tensile and compressive yield strength. The grain size of as-extruded Mg-0.5Sr alloys significantly was refined from 2.78 µm to 1.15 µm due to the pinning effect by fine α-Mn precipitates during the extrusion. Moreover we showed that the tensile yield strength and the compressive yield strength of Mg-0.5Sr-2Mn alloy were 32 and 40 percent age higher than those of Mg-0.5Sr alloy, respectively. Moreover, the strain hardening behaviors of the Mg-0.5Sr-2Mn alloy were discussed, which proved that a large number of small grains and texture have an important role in improving mechanical properties.

Recycling of silicon from silicon cutting waste by Al-Si alloying in cryolite media and its mechanism analysis.

More than 40% of the crystalline silicon has been wasted as silicon cutting waste (SCW) during the wafer production process. This waste not only leads to resource wastage but also causes environmental burden. In this paper, SCW produced by the diamond-wire sawing process was recycled by Al-Si alloying process. Cryolite was introduced to the reaction system to dissolve the SiO2 layer existed on the surface of the Si particles in SCW. Alloys with 12.02 wt% of Si were prepared and the mechanism of the alloying process was investigated in detail. The Si-Al-cryolite system and SiO2-Al-cryolite system were studied individually to analyze the reaction process and transferring behavior of Si and SiO2 in SCW. The SiO2 shell was firstly transformed into Si-O-F ions. Then the Si-O-F ions diffused to the reaction interface by the effect of the concentration gradient and were reduced to Si by the aluminothermic reduction reaction: 4Al (l) + 3SiO2 (dissolved in the melt) = 3Si (Al)+ 2Al2O3 (dissolved in the melt). Then the internal Si particles were released into cryolite after the dissolution of SiO2 and transferred to the reaction interface by the effect of gravity. The influences of the mass ratio of Al/SCW and agitation modes on the Si content of the alloys and the Si recovery ratio in SCW were investigated. With the increase of the mass ratio of Al/SCW from 2.2 to 6.5, the Si recovery ratio in SCW increased from 44.08% to 69.05%, but the silicon content of the alloys decreased from 16.06 wt% to 8.83 wt%. Agitation can effectively improve the smelting effect during smelting by which the silicon content of the alloys and the Si recovery ratio in SCW increased from 12.02 wt% and 64.25% to 13.17 wt% and 69.46%, respectively.

Rab7 regulates primary cilia disassembly through cilia excision.

The primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, we identify the small GTPase Rab7 as a novel regulator of cilia disassembly. Depletion of Rab7 potently induced spontaneous ciliogenesis in proliferating cells and promoted cilia elongation during quiescence. Moreover, Rab7 performs an essential role in cilia disassembly; knockdown of Rab7 blocked serum-induced ciliary resorption, and active Rab7 was required for this process. Further, we demonstrate that Rab7 depletion significantly suppresses cilia tip excision, referred to as cilia ectocytosis, which has been identified as required for cilia disassembly. Mechanically, the failure of F-actin polymerization at the site of excision of cilia tips caused suppression of cilia ectocytosis on Rab7 depletion. Overall, our results suggest a novel function for Rab7 in regulating cilia ectocytosis and cilia disassembly via control of intraciliary F-actin polymerization.