Combination of Plasma Exchange and Adsorption Versus Plasma Exchange in Pediatric Acute Liver Failure: A Multicenter Cohort Study.

OBJECTIVES: This study aimed to compare the efficacy of double plasma molecular adsorption system (DPMAS) with half-dose plasma exchange (PE) to that of full-dose PE in pediatric acute liver failure (PALF). METHODS: This multicenter, retrospective cohort study was conducted in 13 pediatric intensive care units in Shandong Province, China. DPMAS+PE and single PE therapies were performed in 28 and 50 cases, respectively. The patients' clinical information and biochemical data were obtained from the patients' medical records. RESULTS: The severity of illness did not differ between the 2 groups. At 72 hours after treatment, comparing with PE group, the rates of decline of Pediatric model for End-stage Liver Disease and Pediatric Sequential Organ Failure Assessment scores as well as total bilirubin blood ammonia and interleukin-6 were significantly higher, while the short-term effective rate (75.0% vs 44.0%, P = 0.008) was significantly higher in the DPMAS+PE group. The volume of plasma consumption (26.5 vs 51.0 mL/kg, P = 0.000) and the rate of adverse events (3.6% vs 24.0%, P = 0.026) were lower in the DPMAS+PE group than in the PE group, respectively. However, there was no statistical difference in the 28-day mortality between the 2 groups (21.4% vs 40.0%, P > 0.05). CONCLUSIONS: For PALF patients, both DPMAS + half-dose PE and full-dose PE could improve the liver function, while DPMAS + half-dose PE could significantly reduce plasma consumption without obvious adverse effects in contrast with full-dose PE. Thus, DPMAS + half-dose PE may be a suitable alternative method for PALF in the context of the increasingly tight blood supply situation.

First pilot trial of colorectal ESD guided by a new magnetic anchor for ease of placement.

BACKGROUND: In recent years, studies have demonstrated that magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) is feasible and safe and may facilitate the treatment of all difficult lesions. However, the major problem with MAG-ESD is the inability to deliver the magnetic anchor to the gastrointestinal tract without withdrawal or reinsertion of the endoscope. Therefore, our team developed a magnetic anchor that could be easily inserted through the biopsy channel, facilitating ESD traction and evaluated its effectiveness and safety. METHODS: The study was conducted between October 2020 and June 2021 at The Second Affiliated Hospital of Harbin Medical University, China. One hundred and twelve patients with colorectal tumors treated with ESD were divided into two groups for historical control comparison. A channel-placed magnetic anchor (CPMAG) group and a control group consisting of patients who had conventional ESD without adjuvant traction. The rate of en bloc resection and resection with tumor-free lateral/basal margins (R0 resection), dissection speeds, procedure time, intraoperative bleeding and perforation complications, and postoperative follow-up were compared between the two groups, so as to evaluate the clinical effect and safety of the new magnetic anchor. RESULTS: The en bloc resection and R0 resection rate with CPMAG-ESD were slightly higher than with conventional ESD but this was not statistically significant. The median dissection speeds with CPMAG-ESD were higher than with conventional ESD, but the difference was not statistically significant. Intraoperative bleeding and postoperative complications with the CPMAG-ESD were less than with conventional ESD, but this was not statistically significant. The median operating time was shorter with CPMAG- ESD than with conventional ESD (24.5 min [range 15.8-66.5 min] vs 39 min [range 29-58 min], p = 0.024), and this difference was statistically significant. CONCLUSIONS: The new magnetic anchor-guided ESD technique appears to be a feasible and safe method for treating early colorectal tumors with en bloc resection, with improvement of the submucosal visual field, and less adverse events.

New Insight on K2 Zn2 V10 O28 as an Advanced Cathode for Rechargeable Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) have recently attracted people's extensive attention in their application in energy storage systems resulting from their exclusive characteristics of low cost and environmental compatibility. However, finding suitable cathode materials continues to be the major challenge. Polyoxovanadates (POVs), as an important branch of polyoxometalates (POMs), are considered as a promising electrode material for reversible aqueous ZIBs relying on the flexible valence state of V. Herein, POVs (K2 Zn2 V10 O28 : KZVO) are reported as an advanced cathode for storing Zn2+ , which delivers a high discharge capacity of 223.4 mAh g-1 at 0.1 A g-1 , considerable energy density (182.9 Wh kg-1 ) and power density (40.38 W kg-1 ), and robust cyclic performance. In addition, the dynamic properties of the KZVO/Zn battery are revealed by pseudocapacitance analysis and GITT tests. Meanwhile, the storage mechanism of Zn2+ is further analyzed by ex situ XRD, XPS, TEM, and HRTEM. Overall, this work not only draws up a cathode material for the POMs system in aqueous ZIBs, but also demonstrates that POMs are the rising star in energy storage and electric energy applications.

Recent Developments and Challenges of Vanadium Oxides (Vx Oy ) Cathodes for Aqueous Zinc-Ion Batteries.

The rapid depletion of lithium resources and the increasing demand for electrical energy storage have stimulated the pursuit of emerging electrochemical energy storage. Aqueous zinc ion batteries (ZIBs) are highly sought after for their low cost, high safety, and increased environmental compatibility. However, the search for suitable cathode materials is still tricky for a wide range of researchers. Vanadium oxides (Vx Oy ), with their abundant vanadium valence, easily deformable V-O polyhedrons, and tunable chemical compositions, are of significant advantage in developing emerging materials. This work provides a detailed review of different Vx Oy for the application in aqueous ZIBs. The current problems and optimization strategies of Vx Oy cathode materials are systematically discussed. Finally, the current challenges and possible directions for future research of Vx Oy cathode materials in aqueous ZIBs are presented.

LncRNA CDKN2B-AS1 contributes to tumorigenesis and chemoresistance in pediatric T-cell acute lymphoblastic leukemia through miR-335-3p/TRAF5 axis.

T-cell acute lymphoblastic leukemia (T-ALL) is the most prevalent malignancy in children. Long non-coding RNAs are being found to have relevance to the pathogenesis of pediatric T-ALL. However, the function of cyclin-dependent kinase inhibitor 2B anti-sense RNA 1 (CDKN2B-AS1) in pediatric T-ALL progression and chemoresistance has not been illuminated. The levels of CDKN2B-AS1, miR-335-3p and tumor necrosis factor receptor-associated factor 5 (TRAF5) were assessed by quantitative real-time PCR. Cell proliferation and the 50% inhibitory concentration (IC50) value were detected using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium assay. Cell cycle and apoptosis were evaluated by flow cytometry. Western blot analysis was performed to measure protein expression. Targeted interactions among CDKN2B-AS1, miR-335-3p and TRAF5 were determined by the dual-luciferase reporter and RNA immunoprecipitation assays. Animal studies were conducted to observe the function of CDKN2B-AS1 in vivo. Our data indicated that CDKN2B-AS1 was highly expressed in pediatric T-ALL peripheral blood mononuclear cells and cells, and high CDKN2B-AS1 level was associated with adriamycin (ADR) resistance. CDKN2B-AS1 depletion hindered T-ALL/ADR cell proliferation and cell cycle progression, and promoted cell apoptosis and ADR sensitivity in vitro. Moreover, CDKN2B-AS1 knockdown repressed tumor growth and enhanced ADR sensitivity in vivo. CDKN2B-AS1 sequestered miR-335-3p, and CDKN2B-AS1 depletion exerted regulatory effect in T-ALL/ADR cell progression by up-regulating miR-335-3p. TRAF5 was a direct target of miR-335-3p, and TRAF5 mediated the regulation of miR-335-3p in T-ALL cell behaviors. Furthermore, CDKN2B-AS1 positively modulated TRAF5 expression through sponging miR-335-3p. The current work suggested that CDKN2B-AS1 knockdown repressed the progression and enhanced ADR sensitivity of pediatric T-ALL at least partly through targeting miR-335-3p/TRAF5 axis, highlighting a promising therapeutic target for the treatment of pediatric T-ALL patients.

Age-dependent Effects of 17ß-estradiol on the dynamics of estrogen receptor ß (ERß) protein-protein interactions in the ventral hippocampus.

Recent clinical evidence suggests that the neuroprotective and beneficial effects of hormone therapy may be limited by factors related to age and reproductive status. The patient's age and length of time without circulating ovarian hormones are likely to be key factors in the specific neurological outcomes of hormone therapy. However, the mechanisms underlying age-related changes in hormone efficacy have not been determined. We hypothesized that there are intrinsic changes in estrogen receptor ß (ERß) function that determine its ability to mediate the actions of 17ß-estradiol (E2) in brain regions such as the ventral hippocampus. In this study, we identified and quantified a subset of ERß protein interactions in the ventral hippocampus that were significantly altered by E2 replacement in young and aged animals, using two-dimensional differential gel electrophoresis coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry. This study demonstrates quantitative changes in ERß protein-protein interactions with E2 replacement that are dependent upon age in the ventral hippocampus and how these changes could alter processes such as transcriptional regulation. Thus, our data provide evidence that changes in ERß protein interactions are a potential mechanism for age-related changes in E2 responsiveness in the brain after menopause.

Exosome from chaperone-rich cell lysates-loaded dendritic cells produced by CELLine 1000 culture system exhibits potent immune activity.

Dendritic cells (DCs) pulsed with exosomes can stimulate efficient cytotoxic T-lymphocyte responses and anti-tumor immunity. However, the quantity of DC-derived exosomes (DCex) obtained from various culture systems is very low, which is a significant practical issue hampering progress in this research area and needs to be addressed. Gliomas were particularly aggressive, with high morbidity and mortality, indicating that this is a form of incurable highly malignant tumor of the brain with poor prognosis. In the present study, we demonstrate that the CELLine 1000 culture system can dramatically increase the production of DCex. The morphology, phenotype and immune molecules of these DCex were found to be identical to those using traditional methods. Our researches supply a cost-effective, useful method for significantly increasing the quantity of exosomes. In addition, GL261 glioma cells were chosen to separate chaperone-rich cell lysates (CRCL). The results indicate that CRCL-GL261 cell lysates can trigger the most intense expression of immune molecules on DCex or DCs, which has important implications for the research into tumor treatment and diagnosis.

Using the Eeva Test™ adjunctively to traditional day 3 morphology is informative for consistent embryo assessment within a panel of embryologists with diverse experience.

PURPOSE: Since many transferred, good morphology embryos fail to implant, technologies to identify embryos with high developmental potential would be beneficial. The Eeva™ (Early Embryo Viability Assessment) Test, a prognostic test based on automated detection and analysis of time-lapse imaging information, has been shown to benefit embryo selection specificity for a panel of three highly experienced embryologists (Conaghan et al., 2013). Here we examined if adjunctive use of Eeva Test results following morphological assessment would allow embryologists with diverse clinical backgrounds to consistently improve the selection of embryos with high developmental potential. METHODS: Prospective, double-blinded multi-center study with 54 patients undergoing blastocyst transfer cycles consented to have embryos imaged using the Eeva System, which automatically measures key cell division timings and categorizes embryos into groups based on developmental potential. Five embryologists of diverse clinical practices, laboratory training, and geographical areas predicted blastocyst formation using day 3 morphology alone and day 3 morphology followed by Eeva Test results. Odds ratio (OR) and diagnostic performance measures were calculated by comparing prediction results to true blastocyst outcomes. RESULTS: When Eeva Test results were used adjunctively to traditional morphology to help predict blastocyst formation among embryos graded good or fair on day 3, the OR was 2.57 (95 % CI=1.88-3.51). The OR using morphology alone was 1.68 (95 % CI=1.29-2.19). Adjunct use of the Eeva Test reduced the variability in prediction performance across all five embryologists: the variability was reduced from a range of 1.06 (OR=1.14 to 2.20) to a range of 0.45 (OR=2.33 to 2.78). CONCLUSIONS: The Eeva Test, an automated, time-lapse enabled prognostic test, used adjunctively with morphology, is informative in helping embryologists with various levels of experience select embryos with high developmental potential.

Genome-Wide Analysis and Expression of Cyclic Nucleotide-Gated Ion Channel (CNGC) Family Genes under Cold Stress in Mango (Mangifera indica).

The 'king of fruits' mango (Mangifera indica) is widely cultivated in tropical areas and has been threatened by frequent extreme cold weather. Cyclic nucleotide-gated ion channel (CNGC) genes have an important function in the calcium-mediated development and cold response of plants. However, few CNGC-related studies are reported in mango, regardless of the mango cold stress response. In this study, we identified 43 CNGC genes in mango showing tissue-specific expression patterns. Five MiCNGCs display more than 3-fold gene expression induction in the fruit peel and leaf under cold stress. Among these, MiCNGC9 and MiCNGC13 are significantly upregulated below 6 °C, suggesting their candidate functions under cold stress. Furthermore, cell membrane integrity was damaged at 2 °C in the mango leaf, as shown by the content of malondialdehyde (MDA), and eight MiCNGCs are positively correlated with MDA contents. The high correlation between MiCNGCs and MDA implies MiCNGCs might regulate cell membrane integrity by regulating MDA content. Together, these findings provide a valuable guideline for the functional characterization of CNGC genes and will benefit future studies related to cold stress and calcium transport in mango.

Boron-induced activation of Ru nanoparticles anchored on carbon nanotubes for the enhanced pH-independent hydrogen evolution reaction.

As a promising dopant, electron deficient B atom not only tunes the electronic structure of electrocatalysts for improving their intrinsic catalytic activities, but also combines with hydroxy radical as strong adsorption sites for accelerating the water dissociation during the hydrogen evolution reaction (HER). In this paper, we report an electrocatalyst based on boron-modified Ru anchored on carbon nanotubes (B-Ru@CNT) that shows impressive HER activity in acidic and alkaline media. The boron-rich closo-[B12H12]2- borane was selected as a moderately strong reductant for the in situ reduction of a Ru salt, which yielded B-doped Ru nanoparticles. The experimental and theoretical results indicate that the incorporation of B not only weakens the Ru-H bond and downshifts the d-bond centre of Ru from the Fermi level by reducing the electron density at Ru but also accelerates the water dissociation reaction by providing B sites, which strongly adsorb OH* intermediates, and nearby Ru sites, which act as sites for the adsorption of the H* intermediate, thus boosting the HER performance and enhancing the HER kinetics. As a result of the tuning of the electronic structure via B doping, B-Ru@CNT showed excellent HER performance, yielding overpotentials of 17 and 62 mV at a current density of 10 mA cm-2 in alkaline and acidic solutions, respectively. These results indicate that our synthetic method is a promising route to B-doped metallic Ru with enhanced pH-independent HER performance.

Cathode materials for aqueous zinc-ion batteries: A mini review.

Although lithium-ion batteries (LIBs) have many advantages, they cannot satisfy the demands of numerous large energy storage industries owing to their high cost, low security, and low resource richness. Aqueous zinc-ion batteries (ZIBs) with low cost, high safety, and high synergistic efficiency have attracted an increasing amount of attention and are considered a promising choice to replace LIBs. However, the existing cathode materials for ZIBs have many shortcomings, such as poor electron and zinc ion conductivity and complex energy storage mechanisms. Thus, it is crucial to identify a cathode material with a stable structure, substantial limit, and suitability for ZIBs. In this review, several typical cathode materials for ZIBs employed in recent years and their detailed energy storage mechanisms are summarized, and various methods to enhance the electrochemical properties of ZIBs are briefly introduced. Finally, the existing problems and expected development directions of ZIBs are discussed.

Novel weight loss diet attenuates dietary-induced obesity in mice and might correlate with altered gut microbiota and metabolite profiles.

Although many dietary patterns have been studied for weight loss, various limitations still exist. Therefore, we designed a novel weight loss diet (NWLD) with carbohydrate, protein, and fat (energy) contents of 45%, 20%, and 35%, respectively. The saturated fatty acids: monounsaturated fatty acids:polyunsaturated fatty acids ratio was 1:2:1, and the insoluble: soluble dietary fiber ratio was 2:1. We aimed to observe the effect of NWLD on weight loss and understand the underlying metabolic mechanisms. Twenty-nine male C57BL/6J mice were selected. Nine mice were fed ordinary feed in a blank control group, and the rest were fed a high-fat diet (HFD) to establish obese mouse models. Twelve weeks later, obesity models were established, and 10 obese mice were switched to NWLD feeding. Six weeks after switching the diet, the serum, intestinal feces, and kidneys of mice were collected. Obesity-related indicators, gut microbial composition, and fecal metabolite profiles of all the mice were determined, and the correlations among these indicators were analyzed. Kidney function indicators were also assessed. The results showed that the NWLD attenuated HFD-induced weight gain, serum triglycerides (TG), and inflammatory factors, optimized the body composition without kidney function impairment. Amino acid metabolism pathways and metabolites might play key roles in this process. The findings of this research imply that NWLD could be an effective nutritional remedy for managing dietary-induced obesity.

PF-PLC micelles ameliorate cholestatic liver injury via regulating TLR4/MyD88/NF-κB and PXR/CAR/UGT1A1 signaling pathways in EE-induced rats.

Paeoniflorin (PF) has a certain therapeutic effect on cholestasis liver injury. To further improve the bioavailability of PF and play its pharmacological role in liver protection, PF-phospholipid complex micelles (PF-PLC micelles) were prepared based on our previous research on PF-PLC. The protective effects of PF and PF-PLC micelles on cholestasis liver injury induced by 17α-ethynylestradiol (EE) were compared, and the possible mechanisms were further explored. Herein, we showed that PF-PLC micelles effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. Mechanism studies indicated that PF-PLC micelles treatment could suppress the TLR4/MyD88/NF-κB pathway, and further reduce the levels of pro-inflammatory factors. Meanwhile, our experimental results demonstrated that the beneficial effect of PF-PLC micelles on EE-induced cholestasis may be achieved by the upregulation of nuclear receptors and metabolic enzymes (PXR/CAR/UGT1A1). All these results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease.

The complete chloroplast genome of Agave angustifolia.

Agave angustifolia is commonly used for the production of bacanora, a kind of fermented and distilled beverage in Mexico. In the present study, we have successfully assembled its chloroplast genome. The full length of the genome is 157,274 bp with the GC content of 37.84%. There is a large single copy region (LSC) of 85,895 bp, a pair of inverted repeat regions (IR) of 26,575 bp and a small single copy region (SSC) of 18,229 bp in the genome. A total of 132 genes are annotated in the cp genome. Among these, there are 86 protein-coding genes, 38 tRNAs and 8 rRNAs. Phylogenetic analysis reveals that A. angustifolia is closely related with A. H11648.

The complete chloroplast genome of Agave sisalana.

Agave sisalana is one of the Agave cultivars for sisal fiber production around the tropical areas of the world. In the present study, we successfully sequenced and assembled its chloroplast genome. The full size of the genome is 157,268 bp with a GC content at 37.85%. The genome is constructed with a large single copy region (LSC, 85,894 bp), a pair of inverted repeat regions (IR, 26,573 bp) and a small single copy region (SSC, 18,228 bp). Besides, 86 protein-coding genes, 38 tRNAs and 8 rRNAs are annotated on the chloroplast genome. Phylogenetic result reveals that A. sisalana is closely related with A. americana and A. H11648.

The complete chloroplast genome of Agave fourcroydes.

Agave fourcroydes (henequen) is the only cultivated Agave species in the Yucatan Peninsula, which is mainly used for fiber production. In the present study, we have successfully assembled the chloroplast (cp) genome of A. fourcroydes. The full length of the cp genome is 157,291 bp with a GC content at 37.8%. The cp genome is constructed with an inverted repeat region a (IRa) of 26,573 bp, a small single copy region (SSC) of 18,230 bp, an inverted repeat region b (IRb) of 26,573 bp and a large single copy region (LSC) of 85,915 bp. The annotation result reveals 132 genes on the cp genome, including 86 protein-coding genes, 38 tRNAs and 8 rRNAs. Phylogenetic tree reveals that A. fourcroydes is closely related with A. sisalana.

SELDI-TOF as a method for biomarker discovery in the urine of aristolochic-acid-treated mice.

Aristolochic acids (AAs) present in Aristolochia plants are substances responsible for Chinese herbs nephropathy. Recently, strong indications have also been presented, which dietary poisoning with AA is responsible for endemic (Balkan) nephropathy (EN), an enigmatic renal disease that affects rural population living in some countries in Southeastern Europe. A mouse model was applied to follow the effects of two forms of AA, AAI and AAII. SDS-PAGE and SELDI-TOF mass spectrometry with normal phase chips were used to evaluate changes in the urine of treated animals. These two methods are demonstrated to be comparable. The use of SELDI-TOF MS for rapid analysis of a large number of samples and the combination of this method with nano-LC-ESI MS/MS for protein identification were demonstrated. Biomarker discovery after analysis of large cohort of EN patients will be the final aim of these investigations.

Proteomic analysis for process development and control of therapeutic protein separation from human plasma.

The use of proteomics technology during the development of a new process for plasma protein separation was demonstrated. In a two-step process, the two most abundant proteins, HSA and IgG, were removed in a first step of anion-exchange chromatography using a gel with very high capacity. Subsequently, two fractions containing medium and low abundance proteins were re-chromatographed on a smaller column with the same type of gel. Collected fractions were separated by SDS-PAGE and 2-D electrophoresis, and excised proteins were digested with trypsin and identified by LC-ESI-MS/MS. This proteomic analysis proved to be a useful method for detection of low abundance therapeutic proteins and potential harmful contaminants during process development. Based on this method, low abundance therapeutic proteins, such as vitamin-K-dependent clotting factors and inhibitors, could be identified as present in target fractions after chromatographic separation. In addition, the tracking of potentially dangerous impurities and designing proper steps for their removal are important outcomes when developing, refining or controlling a new fractionation schema. For the purpose of in-process control, in-solution digestion of complete fractions followed by protein identification with LC-ESI-MS/MS was demonstrated as a rapid and simple alternative to the entire analysis including 1-D or 2-D electrophoretic steps.

Proteomic characterization of plasma-derived clotting factor VIII-von Willebrand factor concentrates.

Proteomic methods were used to identify the levels of impurities in three commercial plasma-derived clotting factor VIII-von Willebrand factor (FVIII/VWF) concentrates. In all three concentrates, significant amounts of other plasma proteins were found. In Octanate and Haemoctin, two concentrates developed in the 1990s, the major impurities identified were inter-alpha inhibitor proteins, fibrinogen and fibronectin. These two concentrates were also found to contain additional components such as clotting factor II (prothrombin) that are known activators of FVIII. In Wilate, a recently developed FVIII/VWF concentrate, the amount of these impurities was significantly reduced. Batch-to-batch variations and differences between three investigated products were detected using iTRAQ, an isotope labeling technique for comparative MS, demonstrating the potential value of this technique for quality control analysis. The importance of thorough proteomic investigations of therapeutic FVIII/VWF preparations from human plasma is also discussed.

Proteomics as a tool for optimization of human plasma protein separation.

The application of proteomics technology in purification of proteins from human plasma and for characterization of plasma-derived therapeutics has been recently discussed. However, until now, the impact of this technology on the plasma protein fractionation and analysis of the final product has not been realized. In the present work, we demonstrate the use of proteomic techniques the monitoring of the first step of the plasma fractionation by use of anion-exchange chromatography. This chromatographic method is frequently used in the purification scheme for isolation of vitamin K dependent clotting factors II, VII, IX and X, and clotting inhibitors protein C and protein S, as well as inter-alpha inhibitor proteins (IaIp). After the removal of immunoglobulin G and non-binding proteins in the flow-through fraction, albumin and weakly bound proteins were eluted with low concentration of sodium chloride. The proteins that strongly bind to the anion-exchange column were eluted by higher salt concentrations. The fractions of interest were analyzed, and proteins were identified by LC-ESI-MS/MS. By use of this method, not only candidates for therapeutic concentrates, but also some potentially harmful components were identified. This strategy was very helpful for further process optimization, fast identification of target proteins with relatively low abundance, and for the design of subsequent steps in their removal or purification.