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Increased oxidative stress levels play a key role in idiosyncratic drug-induced liver injury (DILI) pathogenesis. To investigated whether advanced oxidation protein products (AOPPs) and ischaemia-modified albumin (IMA) can be used to monitor oxidative stress in DILI patients and to assess disease severity. We performed spectrophotometric assays to assess AOPPs and IMA in 68 DILI patients with severity grade 0–2 (non-severe group), 60 with severity grade 3–5 (severe group), and 38 healthy controls. The results showed that baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios were significantly higher in DILI patients than in healthy controls. Besides, in comparison to the non-severe group, the severe group showed higher baseline AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios. AOPPs and IMA serum levels and AOPPs/albumin and IMA/albumin ratios decreased after treatment in both patient groups. Combining the correlation analysis and areas under the receiver operating curve (AUROCs) analysis results, that IMA outperformed to be one is the most reliable marker to assess disease severity of DILI. Our findings indicated that AOPPs and IMA can serve as key biomarkers for monitoring oxidative stress levels in DILI patients and can indicate disease severity. The IMA outperformed to be one of the most reliable oxidative stress biomarkers to assess disease severity of DILI.

The safe treatment of heavy metals in wastewater is directly related to human health and social development. In this paper, a new type of recyclable adsorbent is synthesized through the oxidation of enhancer and modification with magnetic nanoparticles. The new adsorbent not only inherits the advantages of multiwall carbon nanotubes (6O-MWCNTs), but also exhibits a new magnetic property and further improved adsorption capacity, which is conducive to the magnetic separation and recovery of heavy metals. The adsorption results indicate that multiwall magnetic carbon nanotubes (6O-MWCNTs@Fe3O4) have a good performance for Pb(II) selective adsorption, with a maximum adsorption capacity of 215.05 mg/g, much higher than the existing adsorption capacity of the same type of adsorbents. Under the action of an external magnetic field, 6O-MWCNTs@Fe3O4 that adsorbed metal ions can quickly achieve good separation from the solution. The joint characterization results of FTIR and XPS show that under the action of both coordination and electrostatic attraction, the C=O bond in the –COOH group is induced to open by the metal ions and transforms into an ionic bond, and the metal ions are stably adsorbed on the surface of 6O-MWCNTs@Fe3O4. Pb(II) has a stronger attraction than Cu(II) and Cd(II) to the lone pair of electrons in oxygen atoms to form complexes, due to the covalent index of Pb (6.41) is more larger than that of Cu (2.98) and Cd (2.71).These data provide a new type of recyclable adsorbent for the efficient treatment of heavy metal ions in wastewater and enrich relevant theoretical knowledge.

Naked carp (Gymnocypris przewalskii), endemic to the saline-alkaline Lake Qinghai, have the capacity to tolerate combinations of high salinity and alkalinity, but migrate to spawn in freshwater rivers each year. In this study, we measured the drinking rate over a 24 h period for naked carp exposed to saline-alkaline lake waters with salinities of 15 (L15) and 17 (L17). We also assessed the daily feed intakes of naked carp exposed to L15 and fresh water (FW). Additionally, we studied the daily expression of acid–base regulation and osmoregulation related genes and proteins in the intestine of naked carp exposed to saline-alkaline lake waters. Our results revealed that the drinking rate at night was significantly higher than in daytime when exposed to either L15 or L17, while feed intakes in daytime were significantly higher than at night. The relative expression of Na+/K+-ATPase α (NKA-α), solute carrier family members 26A6 (SLC26A6) and 4A4 (SLC4A4) in the intestine of naked carp exposed to L17 at night was higher than in daytime. Specifically, NKA-α mRNA expression at 4:00 was 7.22-fold and 5.63-fold higher than that at 10:00 and 16:00, respectively, and the expression at 22:00 was 11.29-fold and 8.80-fold higher than that at 10:00 and 16:00, respectively. Similarly, SLC26A6 mRNA expression was greatest at 22:00, exceeding that observed at 4:00, 10:00 and 16:00 by 3.59, 4.44 and 11.14-fold, respectively. Finally, the expression of NKA-α and SLC26A6 protein at the single cell level was also higher at night than during the day, which was 1.65-fold and 1.37-fold higher at 22:00 respectively compared to 16:00. Overall, the present findings revealed that naked carp drinks at night and feeds during the day, demonstrating that intestinal ion regulation exhibits a daily rhythm when exposed to high saline and alkaline lake water.

Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in acute-on-chronic liver failure (ACLF) is still unknown. We aimed to determine the association between serum ammonia level and short-term prognosis in ACLF. Furthermore, we performed an in-depth evaluation of the independent effect of serum ammonia level on the short-term prognosis of hepatitis B virus (HBV) reactivation-induced ACLF patients. We identified 174 patients as part of prospective observational studies in patients with ACLF. Plasma ammonia levels were measured on admission, and several prognostic scores were used to determine the prognostic effect of ammonia. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cut-off points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. Plasma ammonia was significantly higher in nonsurvivors (83.53 ± 43.78 versus 67.13 ± 41.77 µmol/L, P = 0.013), and ACLF patients with hyperammonemia had significantly higher 28-day mortality than those without hyperammonemia. Ammonia was also closely related to ACLF grade (P

Aberrant alternative splicing (AS) has been highly involved in the tumorigenesis and progression of most cancers. The potential role of AS in invasive breast cancer (IBC) remains largely unknown. In this study, RNA sequencing of IBC samples from The Cancer Genome Atlas was acquired. AS events were screened by conducting univariate and multivariate Cox analysis and least absolute shrinkage and selection operator regression. In total, 2146 survival-related AS events were identified from 1551 parental genes, of which 93 were related to prognosis, and a prognostic marker model containing 14 AS events was constructed. We also constructed the regulatory network of splicing factors (SFs) and AS events, and identified DDX39B as the node SF gene, and verified the accuracy of the network through experiments. Next, we performed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in triple negative breast cancer patients with different responses to neoadjuvant chemotherapy, and found that the exon-specific expression of EPHX2, C6orf141, and HERC4 was associated with the different status of patients that received neoadjuvant chemotherapy. In conclusion, this study found that DDX39B, EPHX2 (exo7), and HERC4 (exo23) can be used as potential targets for the treatment of breast cancer, which provides a new idea for the treatment of breast cancer.

The effects of five different microalgae-fungi on nutrient removal and CO2 removal were investigated under three different CO2 contents (35%, 45% and 55%). The results showed that the highest nutrient and CO2 removal efficiency were found at 55% CO2 by cocultivation of different microalgae and fungi. The effect of different initial CO2 concentration on the removal of CO2 from microalgae was significant, and the order of CO2 removal efficiency was 55% (v/v) >45% (v/v) >35% (v/v). The best nutrient removal and biogas purification could be achieved by co-cultivation of C. vulgaris and G. lucidum with 55% initial CO2 content. The maximum mean COD, TN, TP and CO2 removal efficiency can reach 68.29%, 61.75%, 64.21% and 64.68%, respectively under this condition. All highest COD, TN, TP and CO2 removal efficiency were more than 85%. The analysis of energy consumption economic efficiency revealed that this strategy resulted in the highest economic efficiency. The results of this work can promote simultaneously biological purification of wastewater and biogas using microalgal-fungal symbiosis.

Colchicine was commonly used to artificially double chromosomes while the transcriptome changes in colchicine treated plants has rarely been characterized. To understand the molecular mechanism of colchicine on chromosome doubling, we characterized transcriptome data of diploid orchardgrass root after colchicine treatment. Our results showed that 3381 of differentially expressed genes (DEGs) were mainly affected by water stress, 1258 DEGs that were expressed significantly in sample DacR5tr but not in DacR5ck were considered to be mainly affected by colchicine and combination of water and colchicine. These DEGs mainly regulated by colchicine were enriched to gene ontology (GO) accessions of cation binding, catalytic activity, membrane and transporter activity, and enriched to Kyoto Encyclopedia of Genes and Genome (KEGG) pathways of phenylpropanoid biosynthesis, phenylalanine metabolism, plant hormone signal transduction and starch and sucrose metabolism. Genes related to microtubule, spindle, chromosomal kinetochore, vesicle, cellulose and processes of cytoplasm movement, chromatid segregation, membrane and cell wall development were inhibited by colchicine. Our results revealed that colchicine restrained the microtubules and inhibited gene expression of cytokinesis, which might slow down the cell activity, delay the cell into anaerobic respiration, resulting in apoptosis at late stage, and relieving of waterlogging.

In this paper, we investigate second harmonic generation in a single hexagonal GaAs nanowire. An excellent frequency converter based on this nanowire excited using a femtosecond laser is demonstrated to operate over a range from 730 nm to 1960 nm, which is wider than previously reported ranges for nanowires in the literature. The converter always operates with a high conversion efficiency of ~10−5 W−1 which is ~103 times higher than that obtained from the surface of bulk GaAs. This nanoscale nolinear optical converter that simultaneously owns high efficiency and broad bandwidth may open a new way for application in imaging, bio-sensing and on-chip all-optical signal processing operations.

Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient’s quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82.9% of them died within 24 h after irradiation. Furthermore, irradiation induced oxidative stress, microglia accumulation, and inflammation in the cerebellum. Interestingly, blood-brain barrier damage and blood flow reduction was considerably more pronounced in the cerebellum compared to other brain regions. The cerebellar volume decreased by 39% and the migration of proliferating cells to the internal granule layer decreased by 87.5% at 16 weeks after irradiation. In the light of recent studies demonstrating that the cerebellum is important not only for motor functions, but also for cognition, and since treatment of posterior fossa tumors in children typically results in debilitating cognitive deficits, this differential susceptibility of the cerebellum to irradiation should be taken into consideration for future protective strategies.

LIM and SH3 domain protein (LASP-1) is responsible for the development of several types of human cancers via the interaction with other proteins; however, the precise biological functions of proteins interacting with LASP-1 are not fully clarified. Although the role of LASP-1 in hepatocarcinogenesis has been reported, the implication of LASP-1 interactors in HBV-related hepatocellular carcinoma (HCC) is not clearly evaluated. We obtained information regarding LASP-1 interactors from public databases and published studies. Via bioinformatics analysis, we found that LASP-1 interactors were related to distinct molecular functions and associated with various biological processes. Through an integrated network analysis of the interaction and pathways of LASP-1 interactors, cross-talk between different proteins and associated pathways was found. In addition, LASP-1 and several its interactors are significantly altered in HBV-related HCC through microarray analysis and could form a complex co-expression network. In the disease, LASP-1 and its interactors were further predicted to be regulated by a complex interaction network composed of different transcription factors. Besides, numerous LASP-1 interactors were associated with various clinical factors and related to the survival and recurrence of HBV-related HCC. Taken together, these results could help enrich our understanding of LASP-1 interactors and their relationships with HBV-related HCC.

Acquisition of a vancomycin-resistance-determinant may trigger deletion of the mecA gene. However, the molecular mechanisms involved remain largely unknown. In this study, we successfully produced vancomycin-intermediate-resistant Staphylococcus aureus (VISA) from Methicillin-resistant-S. aureus (MRSA) through serial passages with vancomycin. Five MRSA isolates achieved a vancomycin MIC of >8 mg/ml after 45-day serial exposure to vancomycin. After 20-day passages in media without antibiotics, three of the isolates were restored to pre-induction levels, whilst the remaining 2 (3503-1 and 4126-1) retained a vancomycin MIC >6 mg/ml. The oxacillin MICs for strain 3503-1 and its induced equivalents 3503VR6 and 3503VR10, were 512 μg/ml, 431. The deletion region of 3503VR10 was further investigated by whole-genome sequencing. We conclude that transition from MRSA to VISA may cause deletion of the mobile genetic element staphylococcal cassette chromosome mec (SCCmec), and possibly be mediated by IS431, resulting in increased susceptibility to oxacillin.

Liver carcinoma (LC) is a common malignancy worldwide, associated with high morbidity and mortality. Characterizing microbiome profiles of tongue coat may provide useful insights and potential diagnostic marker for LC patients. Herein, we are the first time to investigate tongue coat microbiome of LC patients with cirrhosis based on 16S ribosomal RNA (rRNA) gene sequencing. After strict inclusion and exclusion criteria, 35 early LC patients with cirrhosis and 25 matched healthy subjects were enrolled. Microbiome diversity of tongue coat in LC patients was significantly increased shown by Shannon, Simpson and Chao 1 indexes. Microbiome on tongue coat was significantly distinguished LC patients from healthy subjects by principal component analysis. Tongue coat microbial profiles represented 38 operational taxonomic units assigned to 23 different genera, distinguishing LC patients. Linear discriminant analysis (LDA) effect size (LEfSe) reveals significant microbial dysbiosis of tongue coats in LC patients. Strikingly, Oribacterium and Fusobacterium could distinguish LC patients from healthy subjects. LEfSe outputs show microbial gene functions related to categories of nickel/iron_transport, amino_acid_transport, energy produced system and metabolism between LC patients and healthy subjects. These findings firstly identify microbiota dysbiosis of tongue coat in LC patients, may providing novel and non-invasive potential diagnostic biomarker of LC.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system. However, the mechanisms underlying its tumor initiation, progression and metastasis are not yet fully understood. The annexin A4 (ANXA4) gene is highly expressed in GBC tissues and may play an important role in the initiation and progression of this disease. In this study, we examined the up-regulation of ANXA4 in human GBC tissues and cell lines. Elevated ANXA4 correlated well with invasion depth in GBC patients and predicted a poor prognosis. In vitro, GBC-SD and NOZ cells with ANXA4 knockdown demonstrated increased apoptosis and inhibited cell growth, migration and invasion. Interactions between ANXA4 and nuclear factor-κB (NF-κB) p65 proteins were detected. In vivo, ANXA4 knockdown inhibited tumor growth of GBC cells in nude mice and down-regulated the expression of downstream factors in the NF-κB signaling pathway. Taken together, these data indicate that up-regulation of ANXA4 leads to activation of the NF-κB pathway and its target genes in a feedback regulatory mechanism via the p65 subunit, resulting in tumor growth in GBC.

Accumulating evidences have indicated that the functional -94 ins/del ATTG polymorphism in the promoter region of human nuclear factor-kappa B1 (NFKB1) gene may be associated with cancer risk. However, some studies yielded conflicting results. To clarify precise association, we performed a comprehensive meta-analysis of 42 case-control studies involving 43,000 subjects (18,222 cases and 24,778 controls). The overall results suggested that the -94 ins/del ATTG polymorphism had a decreased risk for cancer, reaching significant levels in five genetic models (dominant model: OR = 0.86, 95% CI = 0.79–0.95, P = 0.002; recessive model: OR = 0.84, 95% CI = 0.74–0.94, P = 0.003; homozygous model: OR = 0.77, 95% CI = 0.66–0.90, P = 0.001; heterozygous model: OR = 0.90, 95% CI = 0.83–0.98, P = 0.011; allelic model: OR = 0.89, 95% CI = 0.83–0.96, P = 0.002). Furthermore, the -94 ins/del ATTG polymorphism could confer a decreased or increased risk for cancer development among Asians and Caucasians, respectively. Additionally, the stratification analysis revealed a significant association between the variant and decreased risk of oral, ovarian and nasopharyngeal cancer in Asians. After we adjusted p values using the Benjamini-Hochberg false discovery rate method to account for multiple comparisons, these associations remained.

The cause of hip osteoarthritis (OA) remains unclear, morphologic abnormality of hip was thought to be a contributing factor to hip OA. The hypothesis was that there were subtle anatomical morphology differences of the hip between normal and OA subjects; the objective of this study was to explore these anatomical differences which are predisposing to hip OA based on CT 3D reconstruction. Ninety-three normal subjects (186 hips) and 66 mild-to-moderate hip OA subjects (132 hips) were recruited in this study. Three parameters of the head-neck relationship were assessed: translation, rotation and concavity. Translation was the potential translational movements of femoral head related to the neck’s axis. Rotation was described by the physeal scar to evaluate the rotation tendency of femoral head related to the neck at the head-neck junction. Concavity was used to assess the sphericity of the head as it joins the neck. The femoral neck anteversion angle and some parameters of the acetabulum: anteversion, inclination and CE angle were measured too. By comparison, it was found that OA subjects had less femoral head sphericity, head-neck junction concavity, acetabular and femoral neck anteversion angle; but greater acetabular coverage. These characteristics increased the risk of hip OA in OA subjects.

Periodontitis is an infective process that ultimately leads to destruction of the soft and hard tissues that support the teeth (the periodontium). Periodontitis has been proposed as a candidate risk factor for development of the autoimmune disease rheumatoid arthritis (RA). Porphyromonas gingivalis, a major periodontal pathogen, is the only known prokaryote expressing a peptidyl arginine deiminase (PAD) enzyme necessary for protein citrullination. Antibodies to citrullinated proteins (anti-citrullinated protein antibodies, ACPA) are highly specific for RA and precede disease onset. Objective of this study was to assess P. gingivalis PAD (PPAD) gene expression and citrullination patterns in representative samples of P. gingivalis clinical isolates derived from periodontitis patients with and without RA and in related microbes of the Porphyromonas genus. Our findings indicate that PPAD is omnipresent in P. gingivalis, but absent in related species. No significant differences were found in the composition and expression of the PPAD gene of P. gingivalis regardless of the presence of RA or periodontal disease phenotypes. From this study it can be concluded that if P. gingivalis plays a role in RA, it is unlikely to originate from a variation in PPAD gene expression.

There exists a wealth of means of efficient utilization of solar energy in nature, with photosynthesis of chlorophylls as a prime example. Separately, artificially structured plasmonic materials are versatile in light harvesting and energy conversion. Using a simple and scalable design of near-percolating silver nanostructures, we demonstrate that the light-harvesting efficiency of chlorophylls can be drastically enhanced by tuning the plasmon frequency of the constituent silver nanoparticles to coincide with the maximal photon flux of sunlight. In particular, we show that the photon upconversion efficiency can be readily enhanced by over 20 folds, with the room-temperature fluorescence quantum yield increased by a factor of 2.63. The underlying mechanism for the upconversion enhancement is attributed to a one-electron-per-photon anti-Stokes process, involving absorption of a characteristic phonon mode of the chlorophylls. These findings suggest that chlorophylls can serve as molecular building blocks for high-efficiency light harvesting and solar energy conversion.