Size-dependent deleterious effects of nano- and microplastics on sperm motility.

INTRODUCTION: Growing concerns regarding the reproductive toxicity associated with daily life exposure to micro-/nano-plastics (abbreviated as MNPs) have become increasingly prevalent. In reality, MNPs exposure involves a heterogeneous mixture of MNPs of different sizes rather than a single size. METHODS: In this study, an oral exposure mouse model was used to evaluate the effects of MNPs of four size ranges: 25-30 nm, 1-5 µm, 20-27 µm, and 125-150 µm. Adult male C57BL/6 J mice were administered environmentally relevant concentrations of 0.1 mg MNPs/day for 21 days. After that, open field test and computer assisted sperm assessment (CASA) were conducted. Immunohistochemical analyses of organ and cell type localization of MNPs were evaluated. Testicular transcriptome analysis was carried out to understand the molecular mechanisms. RESULTS: Our result showed that MNPs of different size ranges all impaired sperm motility, with a decrease in progressive sperm motility, linearity and straight-line velocity of sperm movement. Alterations did not manifest in animal locomotion, body weight, or sperm count. Noteworthy effects were most pronounced in the smaller MNPs size ranges (25-30 nm and 1-5 µm). Linear regression analysis substantiated a negative correlation between the size of MNPs and sperm curvilinear activity. Immunohistochemical analysis unveiled the intrusions of 1-5 µm MNPs, but not 20-27 µm and 125-150 µm MNPs, into Leydig cells and testicular macrophages. Further testicular transcriptomic analysis revealed perturbations in pathways related to spermatogenesis, oxidative stress, and inflammation. Particularly within the 1-5 µm MNPs group, a heightened perturbation in pathways linked to spermatogenesis and oxidative stress was observed. CONCLUSIONS: Our data support the size-dependent impairment of MNPs on sperm functionality, underscoring the pressing need for apprehensions about and interventions against the escalation of environmental micro-/nano-plastics contamination. This urgency is especially pertinent to small-sized MNPs.

A novel benzothiazole-based mononuclear platinum(II) complex displaying potent antiproliferative activity in HepG-2 cells via mitochondrial-mediated apoptosis.

A novel mononuclear platinum(II) complex, [Pt(L-H)Cl] (1, where L= N-(4-(benzo[d]thiazol-2-yl)phenyl)-2-((2-pyridylmethyl)(2-hydroxyethyl)-amino)acetamide), was obtained by covalently tethering a benzothiazole derivative 2-(4-aminophenyl)benzothiazole to the 2-pyridylmethyl-2-hydroxyethylamine chelating PtII center. In vitro tests indicated that complex 1 displayed excellent antiproliferative activity against the tested cancer cell lines, especially liver cancer HepG-2 and SMMC-7221 cells. Importantly, the complex possessed 4.33-fold higher antiproliferative activity as compared with cisplatin against HepG-2 cells, but was less toxic to the normal cell line L02 with the selectivity index (SI = IC50(L02)/IC50(HepG-2)) value of 8.36 compared to cisplatin (SI, 1.40). The results suggested that 1 might have the potential to act as a candidate for the treatment of hepatocellular carcinoma (HCC). Cellular uptake and distribution studies showed that 1 could effectively pass through the membrane of cells, enter the nuclei and mitochondria, induce the platination of cellular DNA. The interaction of 1 with CT-DNA demonstrated that 1 could effectively bind to DNA in a dual binding mode, i.e., the intercalation of the 2-(4-aminophenyl)benzothiazole unit plus monofunctional platination of the platinum(II) moiety. In addition, Hoechst 33342 staining and flow cytometry analysis illustrated that 1 arrested the cell cycle in HepG-2 cancer cells at G2/M phases, induced mitochondrial membrane depolarization, increased ROS generation, and caused obvious cell apoptosis. Further cellular mechanism studies elucidated that 1 triggered HepG-2 cell apoptosis via the mitochondrial-mediated pathway by upregulating the gene and protein expression levels of Bax, downregulating the gene and protein expression levels of Bcl-2, and activating the caspase cascade.

Circulating tumor DNA predicts recurrence and assesses prognosis in operable gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Selecting the appropriate patient for further treatment after surgery for gastric cancer can improve the patient prognosis. Circulating tumor DNA (ctDNA) has the potential to predict recurrence and prognosis after gastric cancer surgery, but the results are still inconclusive. As the completed studies had small sample sizes and were inconsistent, a meta-analysis was conducted to assess the effect of ctDNA on recurrence and prognosis after gastric cancer surgery. METHODS: PubMed, Embase, Scopus, and the Web of Science were searched for potentially eligible studies published up to April 7, 2023. Pooled relative risk (RR) and pooled hazard ratio (HR) were calculated to evaluate recurrence, recurrence-free survival (RFS), and overall survival (OS) following gastric cancer surgery. RESULTS: A pooled analysis revealed that patients who were ctDNA positive before and after surgery were at a high risk of gastric cancer recurrence (RR = 1.79, 95% CI: 1.19-2.71; RR = 3.17, 95% CI: 2.36-4.25). The pooled data revealed that ctDNA-positive patients had a poorer RFS and OS (HR = 6.37, 95% CI: 2.70-15.01; HR = 4.58, 95% CI: 1.68-12.49). CONCLUSIONS: ctDNA-positive patients were at a high risk of recurrence after gastric cancer surgery and had a poorer prognosis. Hence, ctDNA-positive patients needed close follow-up and further treatment.

Machine learning developed a PI3K/Akt pathway-related signature for predicting prognosis and drug sensitivity in ovarian cancer.

BACKGROUND: Ovarian cancer is one of the deadliest malignancies among females, generally having a poor prognosis. The PI3K/Akt pathway plays a vital role in the oncogenesis and progression of many types of cancer. Limited studies have fully clarified the role of PI3K/Akt pathway in the prognosis of ovarian cancer and its correlation with drug sensitivity. METHODS: A prognostic PI3K/Akt pathway related signature (PRS) was constructed with 10 machine learning algorithms using TCGA, GSE14764, GSE26193, GSE26712, GSE63885 and GSE140082 datasets. Gaussian mixture and logistic regression were performed to identify the optimal models for classifying lymphatic and venous invasion. RESULTS: The optimal prognostic PRS developed by Lasso + survivalSVM algorithm acted as an independent risk factor for overall survival (OS) of ovarian cancer patients and had a good performance in evaluating OS rate of ovarian cancer patients. Significant correlation was obtained between PRS-based risk score and Immune score, ESTIMATE score, immune cells and cancer-related hallmarks. Low risk score indicated a lower immune escape score, TIDE score, and higher PD1&CTLA4 immunophenoscore in ovarian cancer. Moreover, PRS-based risk score acted as an indicator for drug sensitivity in the immunotherapy and chemotherapy of ovarian cancer patients. CONCLUSIONS: All in all, our study developed a prognostic PRS showing powerful and good performance in predicting clinical outcome of ovarian cancer patients. PRS could serve as an indicator for drug sensitivity in the chemotherapy and immunotherapy.

Correlation between glycated hemoglobin A1c, urinary microalbumin, urinary creatinine, ß2 microglobulin, retinol binding protein and diabetic retinopathy.

BACKGROUND: Retinopathy is the most common microvascular disease of type 2 diabetes, and seriously threatens the life, health and quality of life of patients. It is worth noting that the development of diabetic retinopathy (DR) can be hidden, with few symptoms. Therefore, the preliminary screening of diabetic patients should identify DR as soon as possible, delay disease progression, and play a vital role in its diagnosis and treatment. AIM: To investigate the correlation between glycated hemoglobin A1c (HbA1c), urinary microalbumin (U-mALB), urinary creatinine (U-CR), mALB/U-CR ratio, ß2 microglobulin (ß2MG), retinol binding protein (RBP) and DR. METHODS: A total of 180 patients with type 2 diabetes mellitus attending the Second People's Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists. Based on whether they had combined retinopathy and its degree, 68 patients with diabetes mellitus without retinopathy (NDR) were assigned to the NDR group, 54 patients with non-proliferative DR (NPDR) to the NPDR group, and 58 patients with proliferative DR to the PDR group. General data, and HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR results were collected from the patients and compared among the groups. Pearson's correlation method was used to analyze the correlation between HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR indices, and multiple linear regression was applied to identify the risk factors for DR. Receiver operator characteristic (ROC) curves were also drawn. RESULTS: The differences in age, gender, systolic and diastolic blood pressure between the groups were not statistically significantly (P > 0.05), but the difference in disease duration was statistically significant (P < 0.05). The differences in fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglyceride between the groups were not statistically significant (P > 0.05). HbA1c in the PDR group was higher than that in the NPDR and NDR groups (P < 0.05). The levels of mALB, ß2MG, RBP, mALB/U-CR and U-CR in the PDR group were higher than those in the NPDR and NDR groups (P < 0.05). Multiple linear regression analysis showed that disease duration, HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR were risk factors for the development of DR. The ROC curve showed that the area under the curve (AUC) for the combination of indices (HbA1c + mALB + mALB/U-CR + U-CR + ß2MG + RBP) was 0.958, with a sensitivity of 94.83% and specificity of 96.72%, which was higher than the AUC for single index prediction (P < 0.05). CONCLUSION: HbA1c, mALB, mALB/U-CR, U-CR, ß2MG and RBP can reflect the development of DR and are risk factors affecting PDR, and the combination of these six indices has predictive value for PDR.

Treatment stratification and prognosis assessment using circulating tumor DNA in locally advanced rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) is an emerging biomarker for locally advanced rectal cancer (LARC), giving hope for stratified treatment. As the completed studies have small sample sizes and different experimental methods, systematic review and meta-analysis were performed to explore their role in predicting pathological complete response (pCR), tumor recurrence, and prognosis. METHODS: PubMed, Embase, and the Web of Science were searched for potentially eligible studies published up to September 6, 2022. Pooled relative risk (RR) was calculated to predict pCR and tumor recurrence, and pooled hazard ratio (HR) was calculated to evaluate the prognosis of overall survival (OS), recurrence-free survival (RFS), and metastasis-free survival (MRS). RESULTS: Twelve studies published between 2018 and 2022 included 931 patients, and 2544 serum samples were eventually included in the meta-analysis. The pooled revealed that ctDNA-negative patients were more likely to have a pCR (RR = 1.64, 95% confidence interval [CI]: 1.26-2.12). The pooled revealed that ctDNA-positive patients were at high risk of recurrence (RR = 3.37, 95% CI: 2.34-4.85) and had a poorer prognosis for OS (HR = 3.03, 95% CI: 1.86-4.95), RFS (HR = 7.08, 95% CI: 4.12-12.14), and MRS (HR = 2.77, 95% CI: 2.01-3.83). CONCLUSION: ctDNA may be useful for stratifying treatment and assessing prognosis in patients with LARC, but its clinical application still needs to be confirmed in a prospective multicenter study with large samples.

Rhein Inhibited Ferroptosis and EMT to Attenuate Diabetic Nephropathy by Regulating the Rac1/NOX1/ß-Catenin Axis.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious complications of diabetes. Rhein has been reported to be effective in treating DN. This study aimed to investigate the role and mechanism of rhein in the treatment of DN. METHODS: High glucose-induced (HG) podocyte injury model and streptozocin-induced (STZ) DN mouse model were constructed and intervened with rhein. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) level was measured by flow cytometry. The expression of Ras-related C3 botulinum toxin substrate 1 (Rac1), NADPH Oxidase 1 (NOX1), and ß-catenin were measured by quantitative real-time PCR (RT-qPCR). The contents of glutathione peroxidase 4 (GPX4), α-smooth muscle actin (α-SMA), Nephrin, and Podocin were characterized by immunofluorescence (IF) staining. Hematoxylin-eosin (HE) staining and Masson staining were employed to observe the renal morphological changes and tubulointerstitial fibrosis. The contents of α-SMA and Nephrin were detected by immunohistochemistry (IHC) staining. The kits were utilized to analyze various biochemical indicators. RESULTS: Rhein inhibited the HG-induced accumulation of ROS, malondialdehyde (MDA), and Fe2+, and the expression of α-SMA, Transferrin Receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), Vimentin, Snail, and Desmin. Rhein inhibited the expression of Rac1 and its downstream targets NOX1 and ß-catenin. Rac1 silencing (si-Rac1) inhibited the accumulation of MDA and Fe2+ and the expression of Rac1, NOX1, ß-catenin, α-SMA, TFR1, and ACSL4. Rac1 overexpression (oe-Rac1) resulted in the inhibition of superoxide dismutase (SOD), glutathione (GSH), GPX4 synthesis, and down-regulation of Recombinant Solute Carrier Family 7, Member 11 (SLC7A11) and Nephrin expression in HG-treated podocytes. Rac1 Lentivirus (LV-Rac1) injection significantly promoted the accumulation of MDA and Fe2+ and increased the expression of RAC1, NOX1, ß-catenin, TFR1, ACSL4, and α-SMA in DN mice. CONCLUSIONS: Rhein inhibited ferroptosis and epithelial-mesenchymal transition (EMT) to attenuate DN by regulating the Rac1/NOX1/ß-catenin axis.

Circulation tumour DNA in predicting recurrence and prognosis in operable colorectal cancer patients: A meta-analysis.

BACKGROUND: Selecting the appropriate patient for further treatment after surgery and adjuvant chemotherapy (ACT) for colorectal cancer (CRC) can improve the patient's prognosis. Circulating tumour DNA (ctDNA) has the potential to predict recurrence and prognosis after CRC surgery and ACT, but the results are still inconclusive. OBJECTIVES: As the completed studies have small sample sizes and different experimental methods, a meta-analysis was conducted to assess the ctDNA on recurrence and prognosis after CRC surgery and ACT. METHODS: PubMed, Embase, the Web of Science and the Cochrane Library were searched for potentially eligible studies published up to 6 March 2022. Pooled relative risk (RR) and pooled hazard ratio (HR) were calculated to evaluate recurrence and the prognosis of recurrence-free survival (RFS) following CRC surgery and ACT. RESULTS: Fourteen studies published between 2014 and 2022 included 2393 patients, and 7189 serum samples were eventually included in the meta-analysis. The pooled revealed that ctDNA-positive patients were at high risk of recurrence after CRC surgery (RR = 4.43, 95% CI: 3.58-5.48, p < .05) and had a poorer prognosis for RFS (HR = 7.26, 95% CI: 5.48-9.62, p < .05). The pooled revealed that ctDNA-positive patients were at high risk of recurrence after ACT (RR = 5.77 95% CI: 4.33-7.69, p < .05) and had a poorer prognosis for RFS (HR = 13.96, 95% CI: 8.71-22.4, p < .05). CONCLUSION: ctDNA-positive patients were at a high risk of recurrence after CRC surgery and ACT and had a poorer prognosis. Hence, ctDNA-positive patients required close follow-up and further treatments.

Diagnostic Accuracy of Wireless Capsule Endoscopy in Polyp Recognition Using Deep Learning: A Meta-Analysis.

Aim: As the completed studies have small sample sizes and different algorithms, a meta-analysis was conducted to assess the accuracy of WCE in identifying polyps using deep learning. Method: Two independent reviewers searched PubMed, Embase, the Web of Science, and the Cochrane Library for potentially eligible studies published up to December 8, 2021, which were analysed on a per-image basis. STATA RevMan and Meta-DiSc were used to conduct this meta-analysis. A random effects model was used, and a subgroup and regression analysis was performed to explore sources of heterogeneity. Results: Eight studies published between 2017 and 2021 included 819 patients, and 18,414 frames were eventually included in the meta-analysis. The summary estimates for the WCE in identifying polyps by deep learning were sensitivity 0.97 (95% confidence interval (CI), 0.95-0.98); specificity 0.97 (95% CI, 0.94-0.98); positive likelihood ratio 27.19 (95% CI, 15.32-50.42); negative likelihood ratio 0.03 (95% CI 0.02-0.05); diagnostic odds ratio 873.69 (95% CI, 387.34-1970.74); and the area under the sROC curve 0.99. Conclusion: WCE uses deep learning to identify polyps with high accuracy, but multicentre prospective randomized controlled studies are needed in the future.

Diagnostic accuracy of probe-based confocal laser endomicroscopy and tissue sampling by endoscopic retrograde cholangiopancreatography in indeterminate biliary strictures: a meta­analysis.

Probe-based confocal laser endomicroscopy (pCLE), also known as optical biopsy, is a new endoscopic technique that provides real-time magnification of 1000 × microscopic tissue information to diagnose indeterminate biliary strictures. Tissue sampling by endoscopic retrograde cholangiopancreatography (ERCP) is routinely performed to evaluate indeterminate biliary strictures. To evaluate the accuracy of pCLE and tissue sampling by ERCP in the diagnosis of indeterminate biliary strictures, 18 articles were included from 2008 to 2021 through Embase, PubMed, Web of Science, and Cochrane library databases. The summary estimates for the pCLE diagnosis of indeterminate biliary strictures were: sensitivity 0.88 (95% confidence interval (CI), 0.84-0.91); specificity 0.79 (95% CI 0.74-0.83); and Diagnostic Odds Ratio (DOR) 24.63 (95% CI 15.76-38.48). The summary estimates for tissue sampling by ERCP diagnosis for indeterminate biliary strictures were: sensitivity 0.54 (95% CI 0.49-0.59); specificity 0.96 (95% CI 0.94-0.98); and DOR 11.31 (95% CI 3.90-32.82). The area under the sROC curve of pCLE diagnosis of indeterminate biliary strictures is 0.90 higher than 0.65 of tissue sampling by ERCP. The pCLE is a better approach than tissue sampling by ERCP for the diagnosis of indeterminate biliary strictures by providing real-time microscopic images of the bile ducts.

Robust and low cost in-fiber acousto-optic Mach-Zehnder interferometer and its application in a dual-wavelength laser.

A robust in-fiber tunable acousto-optic Mach-Zehnder interferometer with a taper-shaped sandwich-like fiber structure is proposed and characterized experimentally, based on which tunable dual-wavelength lasers are demonstrated. The fiber structure was prepared by two-step etching methods, which could be used to fabricate either a symmetric structure for a continuous tuning dual-wavelength laser or an asymmetric structure for a switchable one. The proposed structure has advantages of low cost, low driving power, and robustness. The method for preparing the fiber structure is agile, which paves the way for its applications.

TLR4 knockout ameliorates streptozotocin-induced osteoporosis in a mouse model of diabetes.

Type 1 diabetes mellitus (T1DM) is characterized by hyperglycemia manifesting as insufficient insulin. Toll-like receptor-4 (TLR4) has been implicated in diabetic osteoporosis. We established streptozotocin (STZ)-induced diabetic mouse model and examined the relevant osteoporosis factors in different experimental groups, the WT-CON group, WT-STZ group, KO-CON group and KO-STZ group, respectively. No obvious protection of TLR4 deletion was shown in mice with diabetes. There was no obvious difference in the body weight or blood glucose concentration between WT-STZ group and KO-STZ group. However, TLR4 deletion reduced the receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. Furthermore, TLR4 knockout attenuated STZ-induced diabetic osteoporosis via inhibiting osteoblasts and pre-inflammation factors mediated by the NF-κB pathway. TLR4 deletion ameliorated STZ-induced diabetic osteoporosis in mice, and TLR4 may be used as a potential therapeutic target for the treatment of diabetic osteoporosis.

Association of [1H]-MRS quantified liver fat content with glucose metabolism status.

BACKGROUND: Previous literatures have implied that the liver fat deposition plays a crucial role in the development and progression of insulin resistance. In the present study, we aimed to investigate the association of liver fat content (LFC) with glucose metabolism status in the population of newly diagnosed type 2 diabetes mellitus (nT2DM), prediabetes mellitus (PDM) and normal controls (NC), and assessing if the LFC could as an indicator for the prediction of T2DM. METHODS: A total of 242 subjects (including 141 nT2DM patients, 48 PDM subjects and 53 NC) were enrolled. The levels of LFC were quantified by using the proton magnetic resonance spectroscopy ([1H]-MRS) technique. Clinical and laboratory parameters of study subjects were collected by medical records and biochemical detection. One-way ANOVA or nonparametric test (Kruskal-Wallis) was applied for intergroup comparisons; intergroup comparison was performed in using of Bonferroni multiple-significance-test correction. RESULTS: There were significantly increased LFC levels in nT2DM (14.72% ± 6.37%) than in PDM (9.62% ± 4.41%) and that of NC groups (5.11% ± 3.66%) (all p < 0.001). The prevalence of nonalcoholic fatty liver disease (NAFLD) was also found to be increased in nT2DM (91.48%) than in PDM (85.41%) and that of NC (32.07%) groups. Correlation analysis revealed that the increase of LFC positively associated with fast plasma glucose (FPG), 2 h plasma glucose (PG), Delta G30 and homeostatic model assessment of insulin resistance (HOMA-IR), negatively associated with Delta Ins30, Delta C30, Ins30/G30 AUC, CP30/G30 AUC, Ins AUC/G AUC, CP AUC/G AUC, homeostatic model assessment for ß-cell function index (HOMA-ß) and matsuda insulin sensitivity index (Matsuda ISI). Multilinear regression analysis showed that LFC, body mass index (BMI) and diastolic blood pressure (DBP) contributed for the prediction of HOMA-IR, and total cholesterol (TC), age, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) were the significant contributors for HOMA-ß. CONCLUSIONS: Our study revealed an increased LFC level and prevalence of NAFLD in nT2DM than in PDM and that of NC groups, the increase of LFC was closely associated with insulin resistance and impaired glucose metabolism status, may be regarded as potential indicator contributing to the development and progression of T2DM.

Morula transfer achieves better clinical outcomes than post-thawed cleavage embryos after overnight culture in frozen embryo transfer (FET) cycles.

PURPOSE: This study aimed to investigate the clinical outcomes of morula stage transfer derived from post-thawed cleavage embryos undergoing overnight culture in frozen embryo transfer (FET) cycles. METHODS: We performed a retrospective study that included 392 FET cycles with 784 thawed embryos undergoing overnight culture between January 2014 and December 2018. Embryos were divided into three groups in terms of their status: 8-16 cells without morula (group I), one morula (group II), and two morulae (group III). The clinical outcomes of these cycles were then compared between the three groups. Logistic regression analysis was performed to control for confounders. RESULTS: Group III was associated with a significantly higher clinical pregnancy rate (odds ratio [OR] 2.35; 95% confidence interval [CI] 1.29-4.27; P = 0.005), implantation rate (OR 3.00; CI 1.75-5.16; P < 0.001), multiple pregnancy rate (OR 4.91; CI 2.11-11.40; P < 0.001), and live birth rate (OR 1.96; CI 1.10-3.49; P = 0.022) than group I. Group II had a higher live birth rate than group I after adjustment (OR 1.70; CI 1.04-2.79; P = 0.035). There was no difference in the rate of premature delivery when compared across the three groups after adjustment. CONCLUSION: The transfer of morula stage embryos following the overnight culture of post-thawed cleavage embryos led to an improvement in the clinical outcomes of FET cycles. It is important to reduce the number of morula embryos transferred in order to achieve a singleton pregnancy.

Overexpression of AtAGT1 promoted root growth and development during seedling establishment.

KEY MESSAGE: Arabidopsis photorespiratory gene AtAGT1 is important for the growth and development of root, the non-photosynthetic organ, and it is involved in a complex metabolic network and salt resistance. AtAGT1 in Arabidopsis encodes an aminotransferase that has a wide range of donor:acceptor combinations, including Asn:glyoxylate. Although it is one of the photorespiratory genes, its encoding protein has been suggested to function also in roots to metabolize Asn. However, experimental data are still lacking. In this study, we investigated experimentally the function of AtAGT1 in roots and our results uncovered its importance in root development during seedling establishment after seed germination. Overexpression of AtAGT1 in roots promoted both the growth of primary root and outgrowth of lateral roots. To further elucidate the molecular mechanisms underlying, amino acid content and gene expression in roots were analyzed, and results revealed that AtAGT1 is involved in a complex metabolic network and salt resistance of roots.

The neurovascular protective effect of alogliptin in murine MCAO model and brain endothelial cells.

Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.

Apelin-13 deficiency alters cortical bone geometry, organic bone matrix, and inhibits Wnt/ß-catenin signaling.

Adipokines play key roles in the regulation of obesity, type 2 diabetes mellitus, and bone growth. As a newly discovered hormone in the adipokines family, the precise role of Apelin-13 on bone metabolism is not yet clear. Apelin-13 and 25(OH)D3 expression were detected in freshly isolated serum of healthy individuals and osteoporosis patients with ELISA method. Apelin-13 deficient mice were set up and cortical bone geometry was measured with micro-computed tomography (Micro-CT) at 5 months old, then profile of organic bone matrix genes was detected with quantitative Real-Time PCR (qRT-PCR). Wnt/ß-catenin signaling molecules were assayed in primary osteocytes isolated from neonatal calvarias. Apelin-13 and 25(OH)D3 showed decreased expression in osteoporosis patients. Five-month-old Apelin deficient mice exhibited decreased total and bone marrow cavity area and periosteal and endocortical bone surface. Deficiency of Apelin-13 downregulated collagen maturation associated genes (loxl3 and loxl4) and Wnt/ß-catenin signaling, while loxl2 was upregulated, all of which indicated that Apelin-13 could play a role in regulating skeletal homeostasis. The decrease in bone formation in Apelin-13 deficient mice is associated with downregulation of organic bone matrix genes and Wnt/ß-catenin signaling molecules, all of these indicate that association of Apelin-13 with bone mineral density (BMD) could be mediated by Wnt/ß-catenin pathway.

Contrast-induced nephropathy in patients with diabetes mellitus between iso- and low-osmolar contrast media: A meta-analysis of full-text prospective, randomized controlled trials.

PURPOSE: This study was conducted to compare iso-osmolar contrast medium, iodixanol, with low-osmolar contrast media (LOCM) for assessing contrast-induced nephropathy (CIN) incidence, exclusively in the diabetic population. METHOD: A systematic search was conducted for full-text, prospective, randomized controlled trials (RCTs). The primary outcome was incidence of CIN. Medline, Cochrane Central Register of Controlled Trials, and other sources were searched until May 31, 2017. RESULTS: Twelve RCTs finally met the search criteria. Iodixanol did not significantly reduce the risk of CIN (risk ratio [RR]: 0.72, 95% confidence interval (CI): [0.49, 1.04], p = 0.08). However, there was significantly reduced risk of CIN when iodixanol was compared to a LOCM agent iohexol (RR: 0.32, 95% CI [0.12, 0.89]). There were no differences between iodixanol and the other non-iohexol LOCM (RR: 0.92, 95% CI [0.68, 1.25]). CONCLUSION: In diabetic populations, iodixanol is not associated with a significant reduction of CIN risk. Iodixanol is associated with a reduced risk of CIN compared with iohexol, whereas no significant difference between iodixanol and other LOCM could be found.

Upregulation of microRNA-18b induces phosphatase and tensin homolog to accelerate the migration and invasion abilities of ovarian cancer.

Ovarian cancer (OC) is the most common cause of mortality from malignant gynecological cancers. Its lethality is mainly a result of tumors that are difficult to detect at the early stage and a lack of effective systemic therapy for advanced status cancer. MicroRNAs (miRNAs/miRs) are a category of single-stranded non-coding small RNAs that bind to their target mRNAs, and aberrant expression levels of miRNAs may serve key roles in regulating cell migration and invasion of various types of human cancer. Previous studies have demonstrated that miR-18b may function as an oncogene in numerous types of tumors, but its role and molecular mechanism in OC remained unclear. The present study demonstrated for the first time that miR-18b expression was significantly upregulated in OC tissues and cells. An increased miR-18b expression level was positively associated with tumor grade and lymph node metastasis. An in vitro assay revealed that exogenous inhibition of miR-18b expression may markedly inhibit OC cell migratory and invasive activities, whereas overexpression of miR-18b enhanced cell migratory and invasive abilities. Of note, using in silico methodologies and luciferase reporter assays, it was demonstrated that phosphatase and tensin homolog (PTEN) was a direct target of miR-18b in OC cells. Furthermore, knockdown of miR-18b expression may significantly decrease mRNA and protein expression levels of endogenous PTEN. The results of the present study highlighted that upregulation of miR-18b was involved in OC cell metastasis by directly targeting PTEN. Inhibition of miR-18b may be a novel effective diagnostic and therapeutic measure for OC.

Tunable dual-wavelength fiber laser with unique gain system based on in-fiber acousto-optic Mach-Zehnder interferometer.

A fast tunable dual-wavelength laser based on in-fiber acousto-optic Mach-Zehnder interferometer (AO-MZI) with new fabrication process is proposed. Not only could the center wavelength of the output laser be optimized with enhanced tuning range about 30 nm by tuning the polarization and the driving frequency of the radio frequency (RF) signal accordingly, but also the spectral spacing between the two output wavelengths could be tuned from ~0 nm to 2.65 nm by controlling the power of the RF signal. The tuning mechanism was also discussed.