Cases of membranous nephropathy (MN) with crescent formation, in the absence of lupus, hepatitis B virus infection, anti-glomerular basement membrane (GBM) nephritis, or antineutrophil cytoplasmic antibody (ANCA), are on record. Clinical presentation and treatment outcomes in these patients are unclear. All patients with biopsy-proven MN diagnosed between years 2008 and 2014 and followed up were enrolled retrospectively. Patients with ANCA, anti-GBM antibodies, lupus, hepatitis B virus infection, or malignance were excluded. Clinical features and outcomes were compared between MN patients with and without crescent. Out of 401 consecutive patients with idiopathic MN, 28 (6.9%) showed crescent formation in 4.9% (2.2%-16.7%) of glomeruli. Mean age of these patients was 50.1 ± 11.1 years, and they presented with heavy proteinuria (6.5 ± 4.8  g/24  h) and hematuria; 21.4% of these patients had declined estimated glomerular filtration rate (<60  mL/min/1.73  m2) on biopsy. Anti-phospholipase A2 receptor antibody was detectable in 79.7% of these patients. These clinical features were comparable to the MN patients without crescent (P > 0.05). Twelve (42.9%) patients received steroids plus immunosuppressive therapy similar to that in patients without crescent (41.3%). Fewer patients with crescents achieved remission (67.9% vs 86.7%, P = 0.029). Crescent formation was a risk factor for no response to the treatments (odds ratio [OR] = 3.1, P = 0.033). Higher percentage of crescents predicted more risk for no remission (OR = 1.2, P = 0.038). Patients with crescents presented more frequencies of abnormal serum creatinine during follow-up (10.7% vs 1.3%, P = 0.031). Crescent formation was also a risk factor for worse renal outcome (relative risk = 10.2, P = 0.046). MN patients with crescents showed unfavorable therapeutic response and tended to have worse renal outcomes. More aggressive treatments and renal protection might be considered to improve the outcomes.

The development of precision nanomedicines to direct nanostructure-based reagents into tumour-targeted areas remains a critical challenge in clinics. Chemical reaction-mediated localization in response to tumour environmental perturbations offers promising opportunities for rational design of effective nano-theranostics. Here, we present a unique microenvironment-sensitive strategy for localization of peptide-premodified upconversion nanocrystals (UCNs) within tumour areas. Upon tumour-specific cathepsin protease reactions, the cleavage of peptides induces covalent cross-linking between the exposed cysteine and 2-cyanobenzothiazole on neighbouring particles, thus triggering the accumulation of UCNs into tumour site. Such enzyme-triggered cross-linking of UCNs leads to enhanced upconversion emission upon 808 nm laser irradiation, and in turn amplifies the singlet oxygen generation from the photosensitizers attached on UCNs. Importantly, this design enables remarkable tumour inhibition through either intratumoral UCNs injection or intravenous injection of nanoparticles modified with the targeting ligand. Our strategy may provide a multimodality solution for effective molecular sensing and site-specific tumour treatment.

Numerous studies have evaluated the association between the angiotensinogen (AGT) T174M polymorphism and ischemic stroke(IS) risk. However, the specific association is still controversial.

Key metabolic enzymes regulatethe fluxes of small compounds to provide the basal substrates for cellular architecture and energy. Some of them are reported to be important carcinogenesis- and metastasis-related genes. In our work, we performed RNA-seq for50 pairs of normal-tumor of hepatocellular carcinoma (HCC) samples and found that the expression of dimethylglycine dehydrogenase (DMGDH) is decreased in HCC. The analysis of protein levels with Western blotting and immunohistochemistry also conformed our findings. It is proven to be a valuable biomarker for both diagnosis and prognosis in three independent datasets. Furthermore, we revealed that DMGDH suppresses migration, invasion and metastasis both in vitro and in vivo. By utilizing gene expression microarray for DMGDH, we identified several possible pathways altered in a DMGDH over-expressing cell line. Among these pathways, we noted that the phosphorylation of Akt-308/473 was significantly suppressed when DMGDH was over-expressed. In summary, our work reveals that DMGDH is a potential valuable biomarker for both diagnosis and prognosisfor HCC, and DMGDH gene expression suppresses metastasis through the Akt signaling pathway.

Electroencephalogram reactivity (EEG-R) is a positive predictive factor for assessing outcomes in comatose patients. Most studies assess the prognostic value of EEG-R utilizing visual analysis; however, this method is prone to subjectivity. We sought to categorize EEG-R with a quantitative approach. We retrospectively studied consecutive comatose patients who had an EEG-R recording performed 1-3 days after cardiopulmonary resuscitation (CPR) or during normothermia after therapeutic hypothermia. EEG-R was assessed via visual analysis and quantitative analysis separately. Clinical outcomes were followed-up at 3-month and dichotomized as recovery of awareness or no recovery of awareness. A total of 96 patients met the inclusion criteria, and 38 (40%) patients recovered awareness at 3-month followed-up. Of 27 patients with EEG-R measured with visual analysis, 22 patients recovered awareness; and of the 69 patients who did not demonstrated EEG-R, 16 patients recovered awareness. The sensitivity and specificity of visually measured EEG-R were 58% and 91%, respectively. The area under the receiver operating characteristic curve for the quantitative analysis was 0.92 (95% confidence interval, 0.87-0.97), with the best cut-off value of 0.10. EEG-R through quantitative analysis might be a good method in predicting the recovery of awareness in patients with post-anoxic coma after CPR.

Mounting studies have illustrated an important role of HOTAIR in cancer progress, but few studies have reported its function in cardiac disease, including cardiac-associated sepsis. This study aimed to investigate the function of HOTAIR in sepsis, involving its association with the level of tumor necrosis factor-alpha (TNF-α), an important inducer of myocardial dysfunction during LPS-induced sepsis.

Primary duck hepatocytes (PDH) displays differential susceptibility to duck hepatitis B virus when maintained in the media supplemented with fetal bovine serum or dimethyl sulfoxide (DMSO) which has been widely used for the maintenance of hepatocytes, and prolonging susceptibility to hepadnavirus. However the mechanism underlying maintenance of susceptibility to hepadnavirus by DMSO treatment remains unclear. In this study, a global transcriptome analysis of PDHs under different culture conditions was conducted for investigating the effects of DMSO on maintenance of susceptibility of PDH to DHBV in vitro. The 384 differential expressed genes (DEGs) were identified by comparisons between each library pair (PDHs cultured with or without DMSO or fresh isolated PDH). We analyzed canonical pathways in which the DEGs were enriched in Hepatic Fibrosis / Hepatic Stellate Cell Activation, Bile Acid Biosynthesis and Tight Junction signaling. After re-annotation against human genome data, the 384 DEGs were pooled together with proteins belonging to hepatitis B pathway to construct a protein-protein interaction network. The combination of decreased expression of liver-specific genes (CYP3A4, CYP1E1, CFI, RELN and GSTA1 et al) with increased expression of hepatocyte-dedifferentiation-associated genes (PLA2G4A and PLCG1) suggested that in vitro culture conditions results in the fading of hepatocyte phenotype in PDHs. The expression of seven DEGs associated with tight junction formation (JAM3, PPP2R2B, PRKAR1B, PPP2R2C, MAGI2, ACTA2 and ACTG2) was up-regulated after short-term culture in vitro, which was attenuated in the presence of DMSO. Those results could shed light on DHBV infection associated molecular events affected by DMSO.

The intestinal epithelium is an important barrier that depends on a complex mixture of proteins and these proteins comprise different intercellular junctions. The purpose of this study was to investigate the postnatal and developmental changes in morphology, intercellular junctions and voltage-gated potassium (Kv) channels in the intestine of piglets during the suckling and post-weaning periods.

The coordinating atoms in polydentate chelates are primarily heteroatoms. We present the first examples of pentadentate chelates with all binding atoms of the chelating agent being carbon atoms, denoted as CCCCC chelates. Having up to five metal-carbon bonds in the equatorial plane has not been previously observed in transition metal chemistry. Density functional theory calculations showed that the planar metallacycle has extended Craig-Möbius aromaticity arising from 12-center-12-electron dπ-pπ π-conjugation. These planar chelates have broad absorption in the ultraviolet-visible-near-infrared region and, thus, notable photothermal performance upon irradiation by an 808-nm laser, indicating that these chelates have potential applications in photothermal therapy. The combination of facile synthesis, high stability, and broad absorption of these complexes could make the polydentate carbon chain a novel building block in coordination chemistry.

Gene co-expression network analysis (GCNA) is widely adopted in bioinformatics and biomedical research with applications such as gene function prediction, protein-protein interaction inference, disease markers identification, and copy number variance discovery. Currently there is a lack of rigorous analysis on the mathematical condition for which the co-expressed gene module should satisfy.

The mycotoxin deoxynivalenol (DON), one of the most common food contaminants, primarily targets the gastrointestinal tract to affect animal and human health. This study was conducted to examine the protective function of glutamic acid on intestinal injury and oxidative stress caused by DON in piglets. Twenty-eight piglets were assigned randomly into 4 dietary treatments (7 pigs/treatment): 1) uncontaminated control diet (NC), 2) NC+DON at 4 mg/kg (DON), 3) NC+2% glutamic acid (GLU), and 4) NC+2% glutamic acid + DON at 4 mg/kg (DG). At day 15, 30 and 37, blood samples were collected to determine serum concentrations of CAT (catalase), T-AOC (total antioxidant capacity), H2O2 (hydrogen peroxide), NO (nitric oxide), MDA (maleic dialdehyde), DAO (diamine oxidase) and D-lactate. Intestinal morphology, and the activation of Akt/mTOR/4EBP1 signal pathway, as well as the concentrations of H2O2, MDA, and DAO in kidney, liver and small intestine, were analyzed at day 37. Results showed that DON significantly (P<0.05) induced oxidative stress in piglets, while this stress was remarkably reduced with glutamic acid supplementation according to the change of oxidative parameters in blood and tissues. Meanwhile, DON caused obvious intestinal injury from microscopic observations and permeability indicators, which was alleviated by glutamic acid supplementation. Moreover, the inhibition of DON on Akt/mTOR/4EBP1 signal pathway was reduced by glutamic acid supplementation. Collectively, these data suggest that glutamic acid may be a useful nutritional regulator for DON-induced damage manifested as oxidative stress, intestinal injury and signaling inhibition.

Aerococcus viridans is a wide spread bacterium in the environment and clinically this organism is associated with different diseases in animals and humans. However, the geno- and phenotypic characterization of A. viridans associated with bovine mastitis has not yet been reported. The objectives of this study were to investigate the genetic and phenotypic diversity of A. viridans isolates using three different molecular methods including 16S rRNA gene sequencing, pulsed-field gel electrophoresis and random amplified polymorphic DNA (RAPD) along with biochemical tests, including antimicrobial susceptibility test. In total, 60 A. viridans strains were cultured from dairy herds presenting with subclinical mastitis. The results of biochemical tests revealed that most of the isolates (75.0%) were accurately identified by API Rapid 20 Strep system and the majority of A. viridans strains (96.7%) were found to be catalase negative, while two (3.3%) isolates were weakly positive. All isolates were resistant to trimethoprim-sulfamethoxazole, followed by streptomycin (96.7%), tetracycline (65.0%) and clindamycin (56.7%) by minimum inhibition concentration-determining broth microdilution technique. As compared to the sequence of 16S rRNA gene, both PFGE and RAPD showed their capacities to discriminate the intra-species diversity of A. viridans. Furthermore, most of the isolates obtained from the same herd or region belonged to the same major RAPD group, which indicated that RAPD is an appropriate assay for tracking the origins of isolates and epidemiological studies of A. viridans. This is a novel approach to use three molecular techniques and to compare their efficiency regarding the genetic diversity of A. viridans. The data suggest that A. viridans associated with subclinical mastitis has a considerable phenotypic and genotypic diversity.

Prompted by preliminary findings, this study was conducted to investigate the impact of zoledronic acid on the cancellous bone microstructure and its effect on the level of β-catenin in a mouse model of postmenopausal osteoporosis.

The present study aimed to examine the neurophysiological mechanisms of the 2,6-diisopropylphenol and N-methyl-D-aspartate (NMDA) receptor antagonist against learning and memory impairment, induced by electroconvulsive therapy (ECT). A total of 48 adult depressed rats without olfactory bulbs were randomly divided into six experimental groups: i) saline; ii) 10 mg/kg MK‑801; iii) 10 mg/kg MK‑801 and a course of ECT; iv) 200 mg/kg 2,6‑diisopropylphenol; v) 200 mg/kg 2,6‑diisopropylphenol and a course of ECT; and vi) saline and a course of ECT. The learning and memory abilities of the rats were assessed using a Morris water maze 1 day after a course of ECT. The hippocampus was removed 1 day after assessment using the Morris water maze assessment. The content of glutamate in the hippocampus was detected using high‑performance liquid chromatography. The expression levels of p‑AT8Ser202 and GSK‑3β1H8 in the hippocampus were determined using immunohistochemical staining and western blot analysis. The results demonstrated that the 2,6‑diisopropylphenol NMDA receptor antagonist, MK‑801 and ECT induced learning and memory impairment in the depressed rats. The glutamate content was significantly upregulated by ECT, reduced by 2,6‑diisopropylphenol, and was unaffected by the NMDA receptor antagonist in the hippocampus of the depressed rats. Tau protein hyperphosphorylation in the hippocampus was upregulated by ECT, but was reduced by 2,6‑diisopropylphenol and the MK‑801 NMDA receptor antagonist. It was also demonstrated that 2,6‑diisopropylphenol prevented learning and memory impairment and reduced the hyperphosphorylation of the Tau protein, which was induced by eECT. GSK‑3β was found to be the key protein involved in this signaling pathway. The ECT reduced the learning and memory impairment, caused by hyperphosphorylation of the Tau protein, in the depressed rats by upregulating the glutamate content.

The relationship between EEG source signals and action-related visual and auditory stimulation is still not well-understood. The objective of this study was to identify EEG source signals and their associated action-related visual and auditory responses, especially independent components of EEG.

Vasa is an essential gene for germ cell development belonging to the DEAD-box family. In this study, we comparatively analyzed the expression characteristics of vasa in diploids, triploids, and tetraploids. The sequences showed high similarity among these fish and other vertebrates, with characteristic domains. Tissue expression analysis revealed that vasa was expressed exclusively in the gonad of different ploidy fishes. During embryogenesis, vasa expression was lower in diploid than in triploid and tetraploid fish, caused by doubling of the genome of tetraploids and abnormal gonads in the triploid fish. In adults, vasa mRNA levels were significantly lower in the testes of sterile triploid fish compared with fertile diploids and tetraploids. In the ovaries, triploid fish showed consistently high expression from the non-breeding season to the breeding season. Immunohistochemistry and western blotting results also supported the abnormal expression of vasa in triploid gonads. This study demonstrates, for the first time, that fish of different ploidy exhibit different expression patterns of vasa that contribute to the differentiation of gonadal development.

The relationships between infections in early life and asthma are not completely understood. Likewise, the clinical relevance of microbial communities present in the respiratory tract is only partially known. A number of microbiome studies analyzing respiratory tract samples have found increased proportions of gamma-Proteobacteria including Haemophilus influenzae, Moraxella catarrhalis, and Firmicutes such as Streptococcus pneumoniae. The aim of this study was to present a new approach that combines RNA microbial identification with host gene expression to characterize and validate metagenomic taxonomic profiling in individuals with asthma.

Autophagy is an intracellular process of homeostatic degradation that promotes cell survival under various stressors. Deoxynivalenol (DON), a fungal toxin, often causes diarrhea and disturbs the homeostasis of the intestinal system. To investigate the function of intestinal autophagy in response to DON and associated mechanisms, we firstly knocked out ATG5 (autophagy-related gene 5) in porcine intestinal epithelial cells (IPEC-J2) using CRISPR-Cas9 technology. When treated with DON, autophagy was induced in IPEC-J2 cells but not in IPEC-J2.Atg5ko cells. The deficiency in autophagy increased DON-induced apoptosis in IPEC-J2.atg5ko cells, in part, through the generation of reactive oxygen species (ROS). The cellular stress response can be restored in IPEC-J2.atg5ko cells by overexpressing proteins involved in protein folding. Interestingly, we found that autophagy deficiency downregulated the expression of endoplasmic reticulum folding proteins BiP and PDI when IPEC-J2.atg5ko cells were treated with DON. In addition, we investigated the molecular mechanism of autophagy involved in the IKK, AMPK, and mTOR signaling pathway and found that Bay-117082 and Compound C, specific inhibitors for IKK and AMPK, respectively, inhibited the induction of autophagy. Taken together, our results suggest that autophagy is pivotal for protection against DON in pig intestinal cells.

There has been fast growing evidence showing that glycolysis plays a critical role in the activation of immune cells. Enhanced glycolysis leads to increased formation of intracellular lactate that is exported to the extracellular environment by monocarboxylate transporter 4 (MCT4). Although the biological activities of extracellular lactate have been well studied, it is less understood how the lactate export is regulated or whether lactate export affects glycolysis during inflammatory activation. In this study, we found that MCT4 is up-regulated by TLR2 and TLR4, but not TLR3 agonists in a variety of macrophages. The increased expression of MCT4 was mediated by MYD88 in a NF-κB-dependent manner. Furthermore, we found that MCT4 is required for macrophage activation upon TLR2 and TLR4 stimulations, as evidenced by attenuated expression of proinflammatory mediators in macrophages with MCT4 knockdown. Mechanistically, we found that MCT4 knockdown leads to enhanced intracellular accumulation of lactate and decreased glycolysis in LPS-treated macrophages. We found that LPS-induced expression of key glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 is diminished in macrophages with MCT4 knockdown. Our data suggest that MCT4 up-regulation represents a positive feedback mechanism in macrophages to maintain a high glycolytic rate that is essential to a fully activated inflammatory response.

Deoxynivalenol (DON) has various toxicological effects in humans and pigs that result from the ingestion of contaminated cereal products. This study was conducted to investigate the protective effects of dietary supplementation with glutamic acid on piglets challenged with DON. A total of 20 piglets weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (5 piglets/treatment): 1) basal diet, negative control (NC); 2) basal diet +4 mg/kg DON (DON); 3) basal diet +2% (g/g) glutamic acid (GLU); 4) basal diet +4 mg/kg DON +2% glutamic acid (DG). A 7-d adaptation period was followed by 30 days of treatment. A metabolite analysis using nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomic technology and the determination of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities for plasma, as well as the activity of Caspase-3 and the proliferation of epithelial cells were conducted. The results showed that contents of low-density lipoprotein, alanine, arginine, acetate, glycoprotein, trimethylamine-N-oxide (TMAO), glycine, lactate, and urea, as well as the glutamate/creatinine ratio were higher but high-density lipoprotein, proline, citrate, choline, unsaturated lipids and fumarate were lower in piglets of DON treatment than that of NC treatment (P<0.05). Compared with DON treatment, dietary supplementation with glutamic acid increased the plasma concentrations of proline, citrate, creatinine, unsaturated lipids, and fumarate, and decreased the concentrations of alanine, glycoprotein, TMAO, glycine, and lactate, as well as the glutamate/creatinine ratio (P<0.05). Addition glutamic acid to DON treatment increased the plasma activities of SOD and GSH-Px and the proliferating cell nuclear antigen (PCNA) labeling indexes for the jejunum and ileum (P<0.05). These novel findings indicate that glutamic acid has the potential to repair the injuries associated with oxidative stress as well as the disturbances of energy and amino acid metabolism induced by DON.