C-C Motif Chemokine Ligand 5 (CCL5) as a Predictive Marker for Non-sentinel Lymph Node Presence in Initial-Stage Breast Cancer with 1-2 Affected Sentinel Lymph Nodes.

The objective of our study was to use quantum dots for the purpose of seeing and detecting C-C motif chemokine ligand 5 (CCL5) inside the tissue of sentinel lymph nodes (SLN) and primary tumors. This endeavor aimed to enhance the accuracy of predicting the condition of non-sentinel lymph nodes and provide valuable insights for making informed treatment choices. We analyzed breast cancer patients who underwent sentinel lymph node biopsy followed by axillary lymph node removal due to one or two positive sentinel lymph nodes at the Second People's Hospital of Wuhu, China, between August 2018 and July 2022. Quantum dot technology was employed to visualize and determine CCL5 in the tissue samples from 84 patients. Out of a group diagnosed with breast cancer, 208 underwent sentinel lymph node biopsy. From this pool, 84 tested positive and subsequently underwent axillary lymph node removal. The presence of distinct orange-red fluorescence, linked to quantum dots, was evident in the cellular components of both primary tumors and positive sentinel lymph node tissues. We found a significant relationship between higher levels of SLNCCL5 and advanced tumor growth (P < 0.05). To understand the predictive value of SLN CCL5 related to non-sentinel lymph node status, we utilized the receiver operating characteristic (ROC) method. The area under the curve (AUC) calculated was 0.745 with a cutoff point of 23.285. Multivariate logistic regression was used to understand the effect of tumor dimensions and SLNCCL5 levels on non-sentinel lymph node status in specific patients. Both the size of the tumor and SLNCCL5 levels were found to have a significant impact (P < 0.05). Data suggested that the presence of positive SLNCCL5 might serve as an assessment parameter for anticipating the condition of non-SLN in cases of breast cancer involving T1 or T2 tumors with one or two positive sentinel lymph nodes.

Protective effect of alizarin on vascular endothelial dysfunction via inhibiting the type 2 diabetes-induced synthesis of THBS1 and activating the AMPK signaling pathway.

BACKGROUND: In this study, we investigated the protective effects of alizarin (AZ) on endothelial dysfunction (ED). AZ has inhibition of the type 2 diabetes mellitus (T2DM)-induced synthesis of thrombospondin 1 (THBS1). Adenosine 5'-monophosphate- activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. PURPOSE: The aim of this study was to investigate the ameliorative effect of AZ on vascular injury caused by T2DM and to reveal the potential mechanism of AZ in high glucose (HG)-stimulated human umbilical vein endothelial cells (HUVECs) and diabetic model rats. STUDY DESIGN: HUVECs, rats and AMPK-/- transgenic mice were used to investigate the mitigating effects of AZ on vascular endothelial dysfunction caused by T2DM and its in vitro and in vivo molecular mechanisms. METHODS: In type 2 diabetes mellitus rats and HUVECs, the inhibitory effect of alizarin on THBS1 synthesis was verified by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB) so that increase endothelial nitric oxide synthase (eNOS) content in vitro and in vivo. In addition, we verified protein interactions with immunoprecipitation (IP). To probe the mechanism, we also performed AMPKα2 transfection. AMPK's pivotal role in AZ-mediated prevention against T2DM-induced vascular endothelial dysfunction was tested using AMPKα2-/- mice. RESULTS: We first demonstrated that THBS1 and AMPK are targets of AZ. In T2DM, THBS1 was robustly induced by high glucose and inhibited by AZ. Furthermore, AZ activates the AMPK signaling pathway, and recoupled eNOS in stressed endothelial cells which plays a protective role in vascular endothelial dysfunction. CONCLUSIONS: The main finding of this study is that AZ can play a role in different pathways of vascular injury due to T2DM. Mechanistically, alizarin inhibits the increase in THBS1 protein synthesis after high glucose induction and activates AMPKα2, which increases NO release from eNOS, which is essential in the prevention of vascular endothelial dysfunction caused by T2DM.

FGF2, LIF, and IGF-1 supplementation improves mouse oocyte in vitro maturation via increased glucose metabolism†.

Chemically defined oocyte maturation media supplemented with FGF2, LIF, and IGF-1 (FLI medium) enabled significantly improved oocyte quality in multiple farm animals, yet the molecular mechanisms behind such benefits were poorly defined. Here, we first demonstrated that FLI medium enhanced mouse oocyte quality assessed by blastocyst formation after in vitro fertilization and implantation and fetal development after embryo transfer. We then analyzed the glucose concentrations in the spent media; reactive oxygen species concentrations; mitochondrial membrane potential; spindle morphology in oocytes; and the abundance of transcripts of endothelial growth factor-like factors, cumulus expansion factors, and glucose metabolism-related genes in cumulus cells. We found that FLI medium enabled increased glucose metabolism through glycolysis, pentose phosphate pathway, and hexosamine biosynthetic pathway, as well as more active endothelial growth factor-like factor expressions in cumulus cells, resulting in improved cumulus cell expansion, decreased spindle abnormality, and overall improvement in oocyte quality. In addition, the activities of MAPK1/3, PI3K/AKT, JAK/STAT3, and mTOR signaling pathways in cumulus cells were assessed by the phosphorylation of MAPK1/3, AKT, STAT3, and mTOR downstream target RPS6KB1. We demonstrated that FLI medium promoted activations of all these signaling pathways at multiple different time points during in vitro maturation.

Panax notoginseng saponin R1 improves glucocorticoid-inhibited airway epithelium repair via glucocorticoid receptor ß.

BACKGROUND: Panax notoginseng saponin R1(PNS-R1), derived from Panax notoginseng roots, promotes wound repair, whereas glucocorticoids can inhibit the repair of airway epithelial damage in asthma. OBJECTIVE: This study investigated whether PNS-R1 counteracts the inhibitory effects of glucocorticoids on the repair of airway epithelial damage in asthma. METHODS: In vivo, female C57BL/6 mice were sensitized, challenged with house dust mites (HDM), and treated with dexamethasone, PNS-R1, and/or adenovirus GRß-shRNA. Airway epithelium damage was examined using pathological sections of the trachea and bronchi, markers of airway inflammation, epithelial cells in bronchoalveolar lavage fluid, and expression of the E-cadherin protein. In vitro, we treated 16HBE cells with dexamethasone, PNS-R1, and/or GRß-siRNA and detected cell proliferation and migration. The expression of GRß and key components of MKP-1 and Erk1/2 were detected by western blotting. RESULTS: In vivo, PNS-R1 reduced airway inflammation, hyperresponsiveness, and mucus hypersecretion; the combination of PNS-R1 and dexamethasone promoted airway epithelial integrity and reduced cell detachment. In vitro, PNS-R1 alleviated the inhibition of bronchial epithelial cell growth, migration, and proliferation by dexamethasone; PNS-R1 promoted GRß expression, inhibited MKP-1 protein expression, and activated MAPK signaling, thereby promoting airway epithelial cell proliferation and repair. CONCLUSIONS: Panax notoginseng saponin R1 alleviated the inhibitory effect of dexamethasone on the repair of airway epithelial damage in asthmatic mice, likely by promoting the proliferation of airway epithelial cells by stimulating GRß expression and activating the MAPK pathway.

Lower incidence of diabetes mellitus in patients with aneurysmal subarachnoid hemorrhage: a large case-control study with propensity score matching.

Background and purpose: Diabetes mellitus (DM) is a well-established cardiovascular risk factor for atherosclerotic disease; however, its effect on the risk of rupture of intracranial aneurysms remains controversial. Herein, we aimed to perform a case-control study to investigate the relationship between DM and aneurysmal subarachnoid hemorrhage (aSAH). Methods: We retrospectively reviewed the data of patients with ruptured or unruptured aneurysms who were treated between 2013 and 2023. Univariate and multivariate analyses were performed. Propensity score matching (PSM) analysis was conducted to evaluate the relationship between DM and risk of aSAH. Results: A total of 4,787 patients with 5,768 intracranial aneurysms were included. Among them, 2,957 (61.8%) were females, 1765 (36.9%) had ruptured aneurysms, and 531 (11.1%) presented with DM. Female sex, current drinking, and hypercholesterolemia were associated with a higher risk of aSAH, whereas old age, former smoking, and DM were associated with a lower risk of aSAH in multivariate analysis (p < 0.05). The incidence of DM (13.4%, 406/3022) in the unruptured group was higher than that in the ruptured group (7.1%, 125/1765) (odds ratio, 0.55; 95% confidence interval, 0.444-0.680) (p < 0.001). After propensity score matching, 530 patients with DM were successfully matched, and DM was still associated with a lower risk of aSAH (odds ratio, 0.24; 95% confidence interval, 0.185-0.313) (p < 0.001). Conclusion: Patients with aSAH have a lower incidence of DM, however, this case-cohort study could not establish a causal relationship. A prospective and large study with long-term follow-up is warranted to establish a causal relationship.

Triggering endogenous Z-RNA sensing for anti-tumor therapy through ZBP1-dependent necroptosis.

ZBP1 senses viral Z-RNAs to induce necroptotic cell death to restrain viral infection. ZBP1 is also thought to recognize host cell-derived Z-RNAs to regulate organ development and tissue inflammation in mice. However, it remains unknown how the host-derived Z-RNAs are formed and how these endogenous Z-RNAs are sensed by ZBP1. Here, we report that oxidative stress strongly induces host cell endogenous Z-RNAs, and the Z-RNAs then localize to stress granules for direct sensing by ZBP1 to trigger necroptosis. Oxidative stress triggers dramatically increase Z-RNA levels in tumor cells, and the Z-RNAs then directly trigger tumor cell necroptosis through ZBP1. Localization of the induced Z-RNAs to stress granules is essential for ZBP1 sensing. Oxidative stress-induced Z-RNAs significantly promote tumor chemotherapy via ZBP1-driven necroptosis. Thus, our study identifies oxidative stress as a critical trigger for Z-RNA formation and demonstrates how Z-RNAs are directly sensed by ZBP1 to trigger anti-tumor necroptotic cell death.

Asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis: A preliminary study.

Background: Anastomotic leakage is a life-threatening complication. Improvement of the anastomosis technique is needed, especially in patients with an inflamed edematous intestine. The aim of our study was to evaluate the safety and efficacy of an asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis in pediatric patients. Methods: A total of 23 patients underwent intestinal anastomosis at the Department of Pediatric Surgery of Binzhou Medical University Hospital. Demographic characteristics, laboratory parameters, anastomosis time, duration of nasogastric tube placement, day of first postoperative bowel movement, complications, and length of hospital stay were statistically analyzed. The follow-up was conducted for 3-6 months after discharge. Results: Patients were divided into two groups: the single-layer asymmetric figure-of-eight suture technique (group 1) and the traditional suture technique (group 2). Body mass index in group 1 was lower than in group 2 (14.43 ± 3.23 vs. 19.38 ± 6.74; P = 0.036). The mean intestine anastomosis time in group 1 (18.83 ± 0.83 min) was less than that in group 2 (22.70 ± 4.11 min; P = 0.005). Patients in group 1 had an earlier first postoperative bowel movement (2.17 ± 0.72 vs. 2.80 ± 0.42; P = 0.023). The duration of nasogastric tube placement in group 1 was shorter than that in group 2 (4.12 ± 1.42 vs. 5.60 ± 1.57; P = 0.043). There was no significant difference in laboratory variables, complication occurrence, and length of hospital stay between the two groups. Conclusion: The asymmetric figure-of-eight single-layer suture technique for intestinal anastomosis was feasible and effective. More studies are needed to compare the novel technique with the traditional single-layer suture.

ANFIS-based forming limit prediction of stainless steel 316 sheet metals.

Effect of microstructure on the formability of the stainless sheet metals is a major concern for engineers in sheet industries. In the case of austenitic steels, existence of strain-induced martensite ([Formula: see text]-martensite) in their micro structure causes considerable hardening and formability reduction. In the present study, we aim to evaluate the formability of AISI 316 steels with different intensities of martensite via experimental and artificial intelligence methods. In the first step, AISI 316 grade steels with 2 mm initial thicknesses are annealed and cold rolled to various thicknesses. Subsequently, the relative area of strain-induced martensite are measured using metallography tests. Formability of the rolled sheets are determined using hemisphere punch test to obtain forming limit diagrams (FLDs). The data obtained from experiments were further utilized to train and validate an artificial neural fuzzy interfere system (ANFIS). After training the ANFIS, predicted major strains by the neural network are compared to a new set experimental results. The results indicate that cold rolling has unfavorable effects on the formability of this type of stainless steels while significantly strengthens the sheets. Moreover, the ANFIS exhibits satisfactory results in comparison to the experimental measurements.

An-Luo-Hua-Xian Pill Improves the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated with Entecavir.

Background and Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis and cancer. As the effectiveness of antiviral therapy to reverse liver fibrosis is limited, We aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with entecavir (ETV). Methods: Treatment-naïve patients with CHB were randomly treated with ETV alone or combined with ALHX (ETV+ALHX) between October 1, 2013 and December 31, 2020. Demographic, laboratory, and liver histology data before and after 78 weeks of treatment were collected. The Ishak fibrosis score (F) was used and fibrosis regression required a decrease in F of ≥1 after treatment. Results: A total of 780 patients were enrolled, and 394 with a second liver biopsy after treatment were included in the per-protocol population, 132 in ETV group and 262 in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group was significantly higher than that of the ETV group at baseline F≥3 patients: 124/211 (58.8%) vs. 45/98 (45.9%), p=0.035. The percentage of patients with a decreased liver stiffness measurement (LSM) was higher in the ETV+ALHX group: 156/211 (73.9%) vs. 62/98 (63.%), p=0.056. Logistic regression analysis showed that ETV combined with ALHX was associated with fibrosis regression [odds ratio (OR)=1.94, p=0.018], and a family history of hepatocellular carcinoma was on the contrary. (OR=0.41, p=0.031). Conclusions: ETV combined with ALHX increased liver fibrosis regression in CHB patients.

Reconstructive endovascular treatment for basilar artery trunk aneurysms: complications and clinical and angiography outcomes.

BACKGROUND: Basilar artery trunk aneurysms (BTAs) are rare intracranial aneurysms. We aim to investigate the procedural complications and clinical and angiographic outcomes of BTAs treated with reconstructive endovascular treatment (EVT). METHODS: We retrospectively reviewed the data of 111 patients with BTAs who underwent reconstructive EVT during 2013-2022. The factors associated with procedural complications and clinical and angiographic outcomes were analyzed. RESULTS: The study included 81 men and 30 women (median age 60 years). Overall, 26 (23.4%) cases presented with subarachnoid hemorrhage and 85 (76.6%) presented with unruptured aneurysms. Periprocedural ischemic and hemorrhagic complications occurred in 29 (26.1%) and 4 (3.6%) cases, respectively. The rate of favorable clinical outcomes was 83.8% (92/111) and the mortality rate was 14.4% (16/111). Angiographic follow-up data were available for 77/95 (81.1%) survivors; 57 (74.0%) and 20 (26%) aneurysms exhibited complete and incomplete obliteration, respectively. Old age, high Hunt and Hess grades (IV-V), hemorrhagic complications, and increased aneurysm size were independent risk factors for unfavorable clinical outcomes (p<0.05). Increased aneurysm size and incomplete aneurysm occlusion on immediate angiography were independent risk factors for incomplete occlusion during follow-up (p<0.05). CONCLUSION: Reconstructive EVTs are a feasible and effective treatment for BTAs but are associated with a high risk of ischemic and hemorrhagic complications and a high mortality rate. Larger aneurysms may predict unfavorable clinical outcomes and aneurysm recurrence during follow-up. Hemorrhagic complications may predict unfavorable clinical outcomes, whereas immediate complete aneurysm occlusion may predict total occlusion during follow-up.

MiR-142-3p as an Indicator of OSA Severity Predicts Prognosis in Lung Adenocarcinoma with OSA.

Purpose: The aim was to explore the correlation between Obstructive sleep apnea (OSA) and Lung adenocarcinoma malignant prognosis and evaluate the miR-142-3p was used as an OSA severity indicator to predict the prognosis of Lung adenocarcinoma patients. Methods: This study comprised of 21 diagnosed lung adenocarcinoma patients with or without OSA. The sleep-related variables and tumor pathology were recorded. Hypoxia-inducible factor-1α (HIF1α) and ki67 expression were analyzed by immunohistochemistry in tumor samples. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess the level of miR-142-3p. Results: Lung adenocarcinoma with OSA showed higher apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and the lower lowest pulse oxygen saturation (LSPO2) compared to Lung adenocarcinoma without OSA (P<0.05), and patients with severer OSA have an advanced TNM stage (P=0.004) and metastasis rate (p=0.032). In addition, OSA may down-regulate the miR-142-3p expression in patients with Lung adenocarcinoma, and the patients with low miR-142-3p expression exhibited severe OSA. MiR-142-3p levels significantly decreased in the advanced TNM stage (p=0.015), and the expression of miR-142-3p was negatively associated with AHI (r= -0.505, p=0.020), ODI (r= -0.513, p=0.017). Conclusion: OSA severity may increase Lung adenocarcinoma malignant prognosis. OSA may down-regulate the expression of miR-42-3p. The expression of miR-142-3p was inversely correlated with AHI and ODI as a surrogate of OSA severity. Additionally, the low miR-142-3p expression level was significantly associated with advanced TNM stage in Lung adenocarcinoma patients.

Ox-LDL-mediated ILF3 overexpression in gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: This study aimed to investigate the relationship of dyslipidemia and interleukin-enhancer binding factor 3 (ILF3) in gastric cancer, and provide insights into the potential application of statins as an agent to prevent and treat gastric cancer. METHODS: The expression levels of ILF3 in gastric cancer were examined with publicly available datasets such as TCGA, and western blotting and immunohistochemistry were performed to determine the expression of ILF3 in clinical specimens. The effects of ox-LDL on expression of ILF3 were further verified with western blot analyses. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) pathway analyses were performed to reveal the potential downstream signaling pathway targets of ILF3. The effects of statins and ILF3 on PI3K/AKT/mTOR signaling pathway, cell proliferation, cell cycle, migration and invasion of gastric cancer cells were investigated with Edu assay, flow cytometry and transwell assay. RESULTS: Immunohistochemistry and western blot demonstrated that the positive expression rates of ILF3 in gastric cancer tissues were higher than adjacent mucosa tissues. The ox-LDL promoted the expression of ILF3 in a time-concentration-dependent manner. ILF3 promoted the proliferation, cell cycle, migration and invasion by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibited the proliferation, cell cycle, migration and invasion of gastric cancer by inhibiting the expression of ILF3. CONCLUSIONS: These findings demonstrate that ox-LDL promotes ILF3 overexpression to regulate gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibits the expression of ILF3, which might be a new targeted therapy for gastric cancer.

Continuous Infusion of Angiotensin IV Protects against Acute Myocardial Infarction via the Inhibition of Inflammation and Autophagy.

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Angiotensin (Ang) IV possesses many biological properties that are not yet completely understood. Therefore, we investigated the function and mechanism of Ang IV in AMI in in vivo and in vitro conditions. AMI was performed by ligation of the left anterior descending coronary artery (LAD) in male C57 mice. Ang IV was continuously infused by a minipump 3 d before AMI for 33 d. The neonatal rat ventricular myocytes (NRVCs) were stimulated with Ang IV and cultured under hypoxic conditions. In vivo, Ang IV infusion significantly reduced the mortality after AMI. By the 7th day after AMI, compared with the AMI group, Ang IV reduced the inflammatory cytokine expression. Moreover, terminal deoxyribonucleotidyl transferase- (TDT-) mediated dUTP nick-end labeling (TUNEL) assay showed that Ang IV infusion reduced AMI-induced cardiomyocyte apoptosis. Compared with AMI, Ang IV reduced autophagosomes in cardiomyocytes and improved mitochondrial swelling and disarrangement, as assessed by transmission electron microscopy. By 30th day after AMI, Ang IV significantly reduced the ratio of heart weight to body weight. Echocardiography showed that Ang IV improved impaired cardiac function. Hematoxylin and eosin (H&E) and Masson staining showed that Ang IV infusion reduced the infarction size and myocardial fibrosis. In vitro, dihydroethidium (DHE) staining and comet assay showed that, compared with the hypoxia group, Ang IV reduced oxidative stress and DNA damage. Enzyme-linked immunosorbent assay (ELISA) showed that Ang IV reduced hypoxia-induced secretion of the tumor necrosis factor- (TNF-) ɑ and interleukin- (IL-) 1ß. In addition, compared with the hypoxia group, Ang IV reduced the transformation of light chain 3- (LC3-) I to LC3-II but increased p62 expression and decreased cardiomyocyte apoptosis. Overall, the present study showed that Ang IV reduced the inflammatory response, autophagy, and fibrosis after AMI, leading to reduced infarction size and improved cardiac function. Therefore, administration of Ang IV may be a feasible strategy for the treatment of AMI.

PARP1 deficiency protects against hyperglycemia-induced neointimal hyperplasia by upregulating TFPI2 activity in diabetic mice.

Diabetes mellitus (DM) promotes neointimal hyperplasia, characterized by dysregulated proliferation and accumulation of vascular smooth muscle cells (VSMCs), leading to occlusive disorders, such as atherosclerosis and stenosis. Poly (ADP-ribose) polymerase 1 (PARP1), reported as a crucial mediator in tumor proliferation and transformation, has a pivotal role in DM. Nonetheless, the function and potential mechanism of PARP1 in diabetic neointimal hyperplasia remain unclear. In this study, we constructed PARP1 conventional knockout (PARP1-/-) mice, and ligation of the left common carotid artery was performed to induce neointimal hyperplasia in Type I diabetes mellitus (T1DM) mouse models. PARP1 expression in the aorta arteries of T1DM mice increased significantly and genetic deletion of PARP1 showed an inhibitory effect on the neointimal hyperplasia. Furthermore, our results revealed that PARP1 enhanced diabetic neointimal hyperplasia via downregulating tissue factor pathway inhibitor (TFPI2), a suppressor of vascular smooth muscle cell proliferation and migration, in which PARP1 acts as a negative transcription factor augmenting TFPI2 promoter DNA methylation. In conclusion, these results suggested that PARP1 accelerates the process of hyperglycemia-induced neointimal hyperplasia via promoting VSMCs proliferation and migration in a TFPI2 dependent manner.

Protein deglycase DJ-1 deficiency induces phenotypic switching in vascular smooth muscle cells and exacerbates atherosclerotic plaque instability.

Protein deglycase DJ-1 (DJ-1) is a multifunctional protein involved in various biological processes. However, it is unclear whether DJ-1 influences atherosclerosis development and plaque stability. Accordingly, we evaluated the influence of DJ-1 deletion on the progression of atherosclerosis and elucidate the underlying mechanisms. We examine the expression of DJ-1 in atherosclerotic plaques of human and mouse models which showed that DJ-1 expression was significantly decreased in human plaques compared with that in healthy vessels. Consistent with this, the DJ-1 levels were persistently reduced in atherosclerotic lesions of ApoE-/- mice with the increasing time fed by western diet. Furthermore, exposure of vascular smooth muscle cells (VSMCs) to oxidized low-density lipoprotein down-regulated DJ-1 in vitro. The canonical markers of plaque stability and VSMC phenotypes were evaluated in vivo and in vitro. DJ-1 deficiency in Apoe-/- mice promoted the progression of atherosclerosis and exaggerated plaque instability. Moreover, isolated VSMCs from Apoe-/- DJ-1-/- mice showed lower expression of contractile markers (α-smooth muscle actin and calponin) and higher expression of synthetic indicators (osteopontin, vimentin and tropoelastin) and Kruppel-like factor 4 (KLF4) by comparison with Apoe-/- DJ-1+/+ mice. Furthermore, genetic inhibition of KLF4 counteracted the adverse effects of DJ-1 deletion. Therefore, our results showed that DJ-1 deletion caused phenotype switching of VSMCs and exacerbated atherosclerotic plaque instability in a KLF4-dependent manner.

Long-term outcomes in Chinese patients with chronic hepatitis B receiving nucleoside/nucleotide analogue therapy in real-world clinical practice: 5-year results from the EVOLVE study.

BACKGROUND: In China, the optimal management of individuals living with chronic HBV infection (CHB) remains an unmet need. The EVOLVE Study was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naive CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies. METHODS: Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or hepatitis B e antigen (HBeAg) status were enrolled from tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virological response (HBV DNA <300 copies/ml) and HBV disease progression. RESULTS: Of the 3,408 patients enrolled, 1,807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based versus ETV group (25.9% versus 13.7%); viral breakthrough was the most common reason in the LAM-based group versus financial reasons in the ETV group. At week 240, the virological response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% versus 2.1%) and genotypic resistance (10.1% versus 1.2%; P<0.0001 for both); significantly lower risk of HBV disease progression (14.0% versus 10.7%; P=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% versus 6.4%) and hepatocellular carcinoma (1.9% versus 0.8%). CONCLUSIONS: This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough and resistance with ETV versus LAM-based therapy. ClinicalTrials.gov NCT01726439.

Remediation of cadmium-contaminated coastal saline-alkaline soil by Spartina alterniflora derived biochar.

Following oil extraction in the wetland of the Yellow River Delta, heavy metal contamination of coastal saline-alkaline soil, especially with cadmium (Cd), has become a serious environmental problem in some regions. Biochar application has been proposed to remedy Cd-contaminated soil, but the remediation effect is related to preparation conditions of biochar (e.g., pyrolysis temperature and raw material) and soil properties. The invasive plant, Spartina alterniflora, produces a high amount of biomass, making it suitable for biochar production in coastal China. We investigated the effect of S. alterniflora-derived biochar (SDB) pyrolyzed at four temperatures (350, 450, 550, and 650 °C) crossed with three addition ratios (1, 5, and 10%) and control on Cd contamination of coastal saline-alkaline soil. Pyrolysis temperature affected pH, surface area, and functional groups of SDB. SDB markedly improved soil pH and soil organic matter, but the degree of improvement was affected by pyrolysis temperature and addition ratio. SDB significantly altered available Cd content in soil, but reduced it only at low pyrolysis temperatures (350 and 450 °C). Available Cd content had a positive correlation with soil pH (R2 = 0.298, P < 0.01), but was not related to salinity and soil organic matter content. Thus, SDB pyrolyzed at 350 °C with 5% addition was optimal for passivating Cd in coastal saline-alkaline soil, since available Cd content in soil decreased mostly (by 26.9%). These findings act as a reference for the development of an application strategy for SDB to ameliorate Cd-contaminated coastal saline-alkaline soil.

Loss of PARP-1 attenuates diabetic arteriosclerotic calcification via Stat1/Runx2 axis.

Accelerated atherosclerotic calcification is responsible for plaque burden, especially in diabetes. The regulatory mechanism for atherosclerotic calcification in diabetes is poorly characterized. Here we show that deletion of PARP-1, a main enzyme in diverse metabolic complications, attenuates diabetic atherosclerotic calcification and decreases vessel stiffening in mice through Runx2 suppression. Specifically, PARP-1 deficiency reduces diabetic arteriosclerotic calcification by regulating Stat1-mediated synthetic phenotype switching of vascular smooth muscle cells and macrophage polarization. Meanwhile, both vascular smooth muscle cells and macrophages manifested osteogenic differentiation in osteogenic media, which was attenuated by PARP-1/Stat1 inhibition. Notably, Stat1 acts as a positive transcription factor by directly binding to the promoter of Runx2 and promoting atherosclerotic calcification in diabetes. Our results identify a new function of PARP-1, in which metabolism disturbance-related stimuli activate the Runx2 expression mediated by Stat1 transcription to facilitate diabetic arteriosclerotic calcification. PARP-1 inhibition may therefore represent a useful therapy for this challenging complication.

Salvianolic acid B improves myocardial function in diabetic cardiomyopathy by suppressing IGFBP3.

BACKGROUND: Salvianolic acid B (Sal B) is the representative component of phenolic acids derived from the dried root and rhizome of Salvia miltiorrhiza Bge. (Labiatae), which has been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, the effect of Sal B on diabetic cardiomyopathy (DCM) is still unclear. METHODS: Type 1 diabetes mellitus was induced in C57BL/6 J mice by streptozotocin (STZ) treatment, whereas meanwhile Salvianolic Acid B (Sal B (15 or 30 mg/kg/d) was intraperitoneally injected for 16 weeks. At the end of this period, cardiac function was assessed by echocardiography, and total collagen deposition was evaluated by Masson's trichrome and Picrosirius Red staining. Human umbilical vein endothelial cells exposed to hypoxia were used to investigate the effect of different doses of Sal B on angiogenesis and tube formation in vitro. Transcriptome sequencing was performed to identify potential targets of Sal B. RESULTS: Sal B ameliorated left ventricular dysfunction and remodeling, and decreased collagen deposition in the heart of diabetic mice. Administration of Sal B increased the expression of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and VEGFA in a dose-dependent manner and promoted angiogenesis both in vivo and in vitro. Furthermore, Sal B reduced HG-induced insulin-like growth factor-binding protein 3 (IGFBP3) expression, induced the phosphorylation of extracellular signal-regulated protein kinase and protein kinase B (AKT) activities, enhanced cell proliferation, and activated VEGFR2/VEGFA signaling in endothelial cells. The underlying mechanisms involve SalB that enhances IGFBP3 promoter DNA methylation and induce nuclear translocation of IGFBP3 in HUVECs under hypoxia. CONCLUSIONS: Sal B promoted angiogenesis and alleviated cardiac fibrosis and cardiac remodeling in DCM by suppressing IGFBP3.

Porous GaN Submicron Rods for Gas Sensor with High Sensitivity and Excellent Stability at High Temperature.

Highly porous GaN submicron rods have been synthesized successfully by a facile hydrothermal method and heat treatment under controlled atmosphere. The morphology and size of the hydrothermal products are tailorable by adjusting the concentration of precursor solutions. Upon calcination in air, the nanorod-assembled GaOOH submicron rods are converted into bundlelike Ga2O3 and into porous GaN submicron rods under an ammonia flow. Gas-sensing characterization demonstrates that the sensors based on porous GaN exhibit high sensitivity and fast response to ethanol vapor, as well as excellent stability and reliability at high temperature. The highly porous GaN submicron rods with a large specific surface area, small grain size, and high length-to-diameter ratio show better response to ethanol. A possible sensing enhancement mechanism is also proposed. This study provides a promising route for the novel synthesis of GaN submicron rods for high-performance gas sensors.