Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis.

Excessive oxidative stress and NLRP3 inflammasome activation are considered the main drivers of inflammatory bowel disease (IBD), and inhibition of inflammasomes ameliorates clinical symptoms and morphological manifestations of IBD. Herein, we examined the roles of NLRP3 activation in IBD and modulation of NLRP3 by sulforaphane (SFN), a compound with multiple pharmacological activities that is extracted from cruciferous plants. To simulate human IBD, we established a mouse colitis model by administering dextran sodium sulfate in the drinking water. SFN (25, 50 mg·kg-1·d-1, ig) or the positive control sulfasalazine (500 mg/kg, ig) was administered to colitis-affected mice for 7 days. Model mice displayed pathological alterations in colon tissue as well as classic symptoms of colitis beyond substantial tissue inflammation. Expression of NLRP3, ASC, and caspase-1 was significantly elevated in the colonic epithelium. The expression of NLRP3 inflammasomes led to activation of downstream proteins and increases in the cytokines IL-18 and IL-1ß. SFN administration either fully or partially reversed these changes, thus restoring IL-18 and IL-1ß, substantially inhibiting NLRP3 activation, and decreasing inflammation. SFN alleviated the inflammation induced by LPS and NLRP3 agonists in RAW264.7 cells by decreasing the levels of reactive oxygen species. In summary, our results revealed the pathological roles of oxidative stress and NLRP3 in colitis, and indicated that SFN might serve as a natural NLRP3 inhibitor, thereby providing a new strategy for alternative colitis treatment.

Warming affects leaf light use efficiency and functional traits in alpine plants: evidence from a 4-year in-situ field experiment.

Introduction: Light use efficiency (LUE) is a crucial determinant of plant productivity, while leaf functional traits directly affect ecosystem functions. However, it remains unclear how climate warming affects LUE and leaf functional traits of dominant species in alpine meadows. Methods: We conducted a 4-year in-situ field warming experiment to investigate the eco-physiological characteristics for a dominant species (Elymus nutans) and a common species (Potentilla anserina) on the Tibetan Plateau. The leaf traits, photosynthesis and fluorescence characteristics were measured, along with the soil physical-chemical properties associated with the two species. Results and discussions: Experimental warming increased the leaf LUE, maximum photochemical efficiency, non-photochemical quenching, relative water content and specific leaf area for both species. However, there was a decrease in leaf and soil element content. Different species exhibit varying adaptability to warming. Increasing temperature significantly increased the photosynthetic rate, stomatal conductance, transpiration rate, total water content, and specific leaf volume of E. nutans; however, all these traits exhibited an opposite trend in P. anserina. Warming has a direct negative impact on leaf LUE and an indirectly enhances LUE through its effects on leaf traits. The impact of warming on plant photosynthetic capacity is primarily mediated by soil nutrients and leaf traits. These results indicate that the two different species employ distinct adaptive strategies in response to climate change, which are related to their species-specific variations. Such changes can confer an adaptive advantage for plant to cope with environmental change and potentially lead to alterations to ecosystem structure and functioning.

Corrigendum to "End Stage Renal Failure Patients With Hemophilia Treated With Peritoneal Dialysis: A Case Series" [Kidney International Reports Volume 7, Issue 12, December 2022, Pages 2639-2646].

[This corrects the article DOI: 10.1016/j.ekir.2022.09.030.].

Pure Red Cell Aplasia Secondary to Parvovirus B19 Infection as a Rare Cause of Anemia in a Dialysis Patient: A Case Report.

Parvovirus B19 infection can cause chronic pure red cell aplasia in immunosuppressed hosts or acute and transient aplastic crises in immunocompetent hosts. In dialysis patients, only transient aplastic crisis induced by parvovirus B19 infection has been reported. We herein report the first case of an adult dialysis patient who developed chronic pure red cell aplasia associated with parvovirus B19 infection. Repeated pneumonia and heart failure may contribute to an immunocompromised status, making the patient more vulnerable to parvovirus B19 infection. This case expands on the differential diagnosis of chronic anemia in patients undergoing dialysis.

Home-based exercise in dialysis patients with end-stage renal disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Lack of exercise may reduce the quality of life, physical capability, and functional capability of dialysis patients. Home-based exercise seems to be a desirable form of low-cost intervention. But the effectiveness of this intervention in the dialysis population is still unclear. The purpose of this meta-analysis is to provide effective evidence to determine the impact of home-based exercise on functional capacity, physical capacity, muscular strength, biochemical parameters, and health-related quality of life among dialysis patients with end-stage renal disease (ESRD). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to May 2023, to identify potential randomized controlled trials (RCTs) assessing the effectiveness of home-based exercise in dialysis patients with ESRD. Two independent reviewers selected studies, extracted data, and assessed the risk of bias using the Cochrane tool. Evidence summary using fixed or random effects for meta-analysis. RESULTS: Twelve RCTs including 1008 dialysis patients met the inclusion criteria. The meta-analysis showed significant effects of home-based exercise on physical capacity. Seven studies reported the results of the 6-min walking test, compared with short-term (0-3 months) home-based exercise (P = 0.76), long-term (3-6 months) interventions (P < 0.001) can significantly improve the results of the 6-min walking test. The results showed that home-based exercise did significantly improve patients' VO2 peak (P = 0.007). Compared with center-based exercise or usual care, home exercise did not significantly improve handgrip strength, quality of life or CRP and other biochemical parameters (P > 0.05). CONCLUSION: The results showed that long-term home-based exercise can improve walking ability. In addition, home-based exercise had the benefit on the VO2 peak of ESRD patients receiving dialysis patients. However, there was no statistically significant difference in handgrip strength, health-related quality of life, CRP, and other biochemical parameters.

Urgent-start peritoneal dialysis in the hemophilia a patient with chronic kidney disease: A case report.

Key Clinical Message: This case illustrates that under comprehensive management of individual and clinical needs, urgent-start peritoneal dialysis can be performed safely without bleeding complications in patients with hemophilia A who developed end-stage renal disease. Patients in these cases can benefit from synthetic strategy. Abstract: Hemophilia A is a serious inherited bleeding disorder resulting from a deficiency of coagulation factor VIII (FVIII). Chronic kidney disease (CKD) involvement in hemophilia is relatively rare, but there has been an upward trend in the survival time of patients with prolonged hemophilia. Although peritoneal dialysis (PD) is often used as the first treatment modality for renal replacement treatment, limited data are available on comprehensive management in the hemophilia A population, especially for urgent-start PD. A 56-year-old man who had hemophilia A, was diagnosed with CKD 3 years ago and developed end-stage renal disease was admitted to our hospital after contracting pneumonia and undergoing subsequent Type I respiratory failure. Urgent-start PD improved his condition and health outcomes, and protected his residual renal function. This case is the first study of a Chinese male patient with hemophilia A who developed end-stage renal disease. We summarize the clinical treatment and nursing care strategies of urgent-start PD in a hemophilia A patient with end-stage renal disease. This case illustrates that under comprehensive management of individual and clinical needs, urgent-start PD can be performed safely without bleeding complications in patients with hemophilia A.

Membrane Curvature: The Inseparable Companion of Autophagy.

Autophagy is a highly conserved recycling process of eukaryotic cells that degrades protein aggregates or damaged organelles with the participation of autophagy-related proteins. Membrane bending is a key step in autophagosome membrane formation and nucleation. A variety of autophagy-related proteins (ATGs) are needed to sense and generate membrane curvature, which then complete the membrane remodeling process. The Atg1 complex, Atg2-Atg18 complex, Vps34 complex, Atg12-Atg5 conjugation system, Atg8-phosphatidylethanolamine conjugation system, and transmembrane protein Atg9 promote the production of autophagosomal membranes directly or indirectly through their specific structures to alter membrane curvature. There are three common mechanisms to explain the change in membrane curvature. For example, the BAR domain of Bif-1 senses and tethers Atg9 vesicles to change the membrane curvature of the isolation membrane (IM), and the Atg9 vesicles are reported as a source of the IM in the autophagy process. The amphiphilic helix of Bif-1 inserts directly into the phospholipid bilayer, causing membrane asymmetry, and thus changing the membrane curvature of the IM. Atg2 forms a pathway for lipid transport from the endoplasmic reticulum to the IM, and this pathway also contributes to the formation of the IM. In this review, we introduce the phenomena and causes of membrane curvature changes in the process of macroautophagy, and the mechanisms of ATGs in membrane curvature and autophagosome membrane formation.

Association between TH/MAOB gene single nucleotide polymorphisms and excitability in Labrador Retrievers.

Excitability is a pivotal quality in guide dogs because moderately active dogs are more trainable. Excessive activity is associated with behavioral problems and pet surrender. Excitability is a highly heritable trait, yet the relevant genetic factors and markers associated with this condition are poorly characterized. In the present study, we selected six single nucleotide polymorphisms (SNPs) of two genes that are possibly related to excitability in dogs (TH c.264G > A, TH c.1208A > T, TH c.415C > G, TH c.168C > T, TH c.180C > T and MAOB c.199 T > C). We measured the excitability of dogs using seven variables from three behavioral tests: the play test (interest in play, grabbing in throw and tug-of-war), the chase test (following and forward grabbing) and the passive test (moving range and moving time). These behavioral tests are part of the Dog Mentality Assessment developed by Svartberg & Forkman. The activity scores in the guide dog group were higher than in the temperament withdrawal group, and significant differences were detected in the aggregate score (p = 0.02), passive activity score (p = 0.007) and moving range score (p = 0.04). Analysis using the Kruskal-Wallis test and non-parametric Steel-Dwass test to evaluate the relationship between these SNPs and behavioral variable scores revealed that TH c.264G > A was associated with aggregate scores of excitability-related behavioral variables (adj. p = 0.03), object-interaction activity scores (adj. p = 0.03), following scores (adj. p = 0.03) and forward grabbing scores (adj. p = 0.03) in Labrador dogs and MAOB c.199 T > C was associated with moving range scores in these dogs (adj. p = 0.004). However, these results had low power. To explain the behavioral traits, further genetic studies more reliable than candidate gene studies are needed.

End Stage Renal Failure Patients With Hemophilia Treated With Peritoneal Dialysis: A Case Series.

Introduction: Currently, no consensus on optimal renal replacement modality has been reached for end-stage renal disease (ESRD) patients complicated with hemophilia. They may require infusion of coagulation factors during each hemodialysis session. In comparison, peritoneal dialysis (PD) might be preferred considering that coagulation replacement is only required for catheter placement. However, limited data on the safety and efficacy of PD for treating ESRD patients with hemophilia were reported. Methods: This is a single-center retrospective cohort study. ESRD patients diagnosed with hemophilia under PD in Peking Union Medical College Hospital from January 1, 1996 to December 31, 2021 were included and followed-up with every month. Their baseline clinical data, catheter insertion procedure, coagulation factor replacement, complications, and outcome were analyzed and compared with general PD patients. Results: In total, 8 patients diagnosed with hemophilia were included, all-male, with a mean age of 50.3±13.3 years old. Two were acquired hemophilia A, whereas the rest were hereditary hemophilia A (HHA). Seven patients experienced significant hemoglobin (Hgb) increment after PD. Peritoneal hemorrhage only consisted of a small portion of all hemorrhage. Patients with hemophilia seemed to have lower small solute clearance despite higher baseline peritoneal permeability, and appeared to have increased peritonitis rate than other male PD patients, yet this study is not powered to prove this. Conclusion: PD is a safe and effective choice for patients with hemophilia and ESRD requiring dialysis. More studies are required to evaluate this certain rare group of patients.

Environmental filtering rather than dispersal limitation dominated plant community assembly in the Zoige Plateau.

Identifying the mechanisms that underlie the assembly of plant communities is critical to the conservation of terrestrial biodiversity. However, it is seldom measured or quantified how much deterministic versus stochastic processes contribute to community assembly in alpine meadows. Here, we measured the decay in community similarity with spatial and environmental distance in the Zoige Plateau. Furthermore, we used redundancy analysis (RDA) to divide the variations in the relative abundance of plant families into four components to assess the effects of environmental and spatial. Species assemblage similarity liner declined with geographical distance (p < .001, R 2 = .6388), and it decreased significantly with increasing distance of total phosphorus (TP), alkali-hydrolyzable nitrogen (AN), available potassium (AK), nitrate nitrogen (NO3 +-N), and ammonia nitrogen (NH4 +-N). Environmental and spatial variables jointly explained a large proportion (55.2%) of the variation in the relative abundance of plant families. Environmental variables accounted for 13.1% of the total variation, whereas spatial variables accounted for 11.4%, perhaps due to the pronounced abiotic gradients in the alpine areas. Our study highlights the mechanism of plant community assembly in the alpine ecosystem, where environmental filtering plays a more important role than dispersal limitation. In addition, a reasonably controlled abundance of Compositae (the family with the highest niche breadth and large niche overlap value with Gramineae and Cyperaceae) was expected to maintain sustainable development in pastoral production. These results suggest that management measures should be developed with the goal of improving or maintaining suitable local environmental conditions.

Optimal targets of chronic kidney disease-mineral and bone disorder markers for Chinese patients with maintenance peritoneal dialysis: a single-center retrospective cohort study.

BACKGROUND: The chronic kidney disease-mineral and bone disorder（CKD-MBD) is known to be associated with increased mortality in dialysis patients, but whether current global guidelines for CKD-MBD, which were primarily developed from hemodialysis, are suitable for peritoneal dialysis (PD) patients practice require further investigation. METHODS: This is a single-center retrospective cohort study. In total 491 prevalent PD patients (median follow-ups: 34 months) from Peking Union Medical College Hospital (PUMCH) from January 2004 to December 2017 were included and followed until 30 June 2018. In the first dialysis year, the average levels of serum calcium, albumin-corrected calcium (CorCa), phosphorus, and parathyroid hormone (PTH) levels were the interested predictors in Cox proportional regression model. RESULTS: Of these PD patients (age 58 ± 17 years), 52% were male and 36% had diabetic nephropathy. In Cox regression over first-year mean parameters, PTH <100 pg/mL (HR = 1.97, 95% CI 1.32 to 2.94, p < 0.001) and ≥300 pg/mL (HR = 2.24, 95% CI 1.32 to 3.81, p = 0.003) were associated with increased all-cause mortality than that of PTH 100-200 pg/mL. Patients with albumin-corrected serum calcium level < 2.13 mmol/L also had higher risk of death than patients with level of 2.13 to 2.38 mmol/L (HR = 2.06, 95% CI 1.06 to 4.01, p = 0.02). Serum phosphorus ≥1.45 mmol/L were associated with increased all-cause mortality. However, lacking of data on 25-hydroxy vitamin D, alkaline phosphatase, and activated vitamin-D are limitations of our analysis. CONCLUSIONS: As one of the largest PD cohort study focusing on CKD-MBD, we demonstrated that the level of CKD-MBD markers in the first PD year are independent predictors of all-cause mortality. PTH 100-300 pg/mL might be the best target for Chinese PD patients.

Leaf and canopy photosynthesis of four desert plants: considering different photosynthetic organs.

Desert plants evolve different photosynthetic organs to adapt to the extreme environment. We studied the leaf and canopy gas exchange, chlorophyll content, fluorescence parameters, and anatomical structure of different photosynthetic organs (leaf and assimilating stem) on four desert plants (Nitraria sphaerocarpa, Caragana korshinskii, Haloxylon ammodendron, and Calligonum mongolicum). The results showed a higher net photosynthetic rate (PN) in the assimilating stems of H. ammodendron and C. mongolicum, which also had a higher light saturation point and a lower light compensation point than leaves (N. sphaerocarpa and C. korshinskii), suggesting more efficient solar energy utilization in the former. Within each species, canopy apparent photosynthetic rate (CAP) was significantly lower than PN, and the daily average CAP of the assimilating stems was significantly higher than leaves. These findings indicated that the photosynthetic response of desert plants was specific to photosynthetic organs. We concluded that the assimilating stem was a superior adaption for desert plants to survive the arid environments.

Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments.

Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mimic human Inflammatory bowel disease (IBD) by treating drinking water with dextran sodium sulphate or intra-colonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Transcriptomics combined with functional experiments were used to investigate underlying mechanisms. Colitis symptoms, including weight loss and high disease activity index were significantly reversed by naringin. The inflammatory response, oxidative reactions, and epithelial cell apoptosis that occur with colitis were also alleviated by naringin. After naringin treatment, transcriptomics results identified 753 differentially expressed mRNAs that were enriched in signaling pathways, including the neuroactive ligand-receptor interaction, calcium signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. The naringin-induced alleviation of colitis was significantly inhibited by the PPAR-γ inhibitor BADGE. In IEC-6 and RAW264.7 cells incubated with lipopolysaccharide (LPS), NF-κB-p65, a downstream protein of PPAR-γ, was significantly increased. Naringin suppressed LPS-induced high expression of NF-κB-p65, which was inhibited by small interfering RNA targeting PPAR-γ. Our study clarifies detailed mechanisms underlying naringin-induced therapeutic effects on mice colitis, and PPAR-γ was found to be the main target of naringin by functional experiments both in vivo and in vitro. Our study supplies new scientific information for the use of naringin in colitis treatment.

Leaf and Community Photosynthetic Carbon Assimilation of Alpine Plants Under in-situ Warming.

The Tibetan Plateau is highly sensitive to elevated temperatures and has experienced significant climate warming in the last decades. While climate warming is known to greatly impact alpine ecosystems, the gas exchange responses at the leaf and community levels to climate warming in alpine meadow ecosystems remain unclear. In this study, the alpine grass, Elymus nutans, and forb, Potentilla anserina, were grown in open-top chambers (OTCs) for 3 consecutive years to evaluate their response to warming. Gas exchange measurements were used to assess the effects of in-situ warming on leaf- and community-level photosynthetic carbon assimilation based on leaf photosynthetic physiological parameters. We introduced a means of up-scaling photosynthetic measurements from the leaf level to the community level based on six easily measurable parameters, including leaf net photosynthetic rate, fresh leaf mass per unit leaf area, fresh weight of all plant leaves in the community, the percentage of healthy leaves, the percentage of received effective light by leaves in the community, and community coverage. The community-level photosynthetic carbon assimilation and productivity all increased with warming, and the net photosynthetic rate at the leaf level was significantly higher than at the community level. Under elevated temperature, the net photosynthetic rate of E. nutans decreased, while that of P. anserina increased. These results indicated that climate warming may significantly influence plant carbon assimilation, which could alter alpine meadow community composition in the future.

Responses of Plant Bud Bank Characteristics to the Enclosure in Different Desertified Grasslands on the Tibetan Plateau.

Asexual reproduction is the main mode of alpine plant reproduction, and buds play an important role in plant community succession. The purpose of this study is to explore whether the desertified grassland can recover itself through the existing bud bank. The bud bank composition, distribution and size of different desertified grasslands were studied using unit volume excavation on the Tibetan Plateau. The bud bank consisted of tiller, long and short rhizome buds, and more than 40% of buds were distributed in the 0-10 cm soil layer. Enclosure changed the bud density, distribution and composition. The bud densities were 4327 and 2681 No./m2 in light and middle desertified grasslands before enclosure, while that decreased to 3833 and 2567 No./m2 after enclosure. Tiller bud density and proportion of middle desertified grassland were the highest, increased from 2765 (31.26%, before enclosure) to 5556 No./m3 (62.67%, after enclosure). There were new grasses growing out in the extreme desertified grassland after enclosure. The meristem limitation index of moderate desertified grassland was the lowest (0.37), indicating that plant renewal was limited by bud bank. Plants constantly adjust the bud bank composition, distribution, and asexual reproduction strategy, and desertified grasslands can recover naturally, relying on their bud banks through an enclosure.

Ginsenoside Rb1 alleviates colitis in mice via activation of endoplasmic reticulum-resident E3 ubiquitin ligase Hrd1 signaling pathway.

Endoplasmic reticulum (ER) homeostasis is regulated by ER-resident E3 ubiquitin ligase Hrd1, which has been implicated in inflammatory bowel disease (IBD). Ginsenoside Rb1 (GRb1) is the major ginsenoside in ginseng with multiple pharmacological activities. In this study we investigated the role of Hrd1 in IBD and its regulation by GRb1. Two mouse colitis models were established to mimic human IBD: drinking water containing dextran sodium sulfate (DSS) as well as intra-colonic infusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Colitis mice were treated with GRb1 (20, 40 mg·kg-1·d-1, ig) or a positive control drug sulfasalazine (500 mg·kg-1·d-1, ig) for 7 days. The model mice showed typical colitis symptoms and pathological changes in colon tissue. In addition to significant inflammatory responses and cell apoptosis in colon tissue, colon epithelial expression of Hrd1 was significantly decreased, the expression of ER stress markers GRP78, PERK, CHOP, and caspase 12 was increased, and the expression of Fas was increased (Fas was removed by Hrd1-induced ubiquitination). These changes were partially, or completely, reversed by GRb1 administration, whereas injection of Hrd1 inhibitor LS102 (50 mg·kg-1· d-1, ip, for 6 days) exacerbated colitis symptoms in colitis mice. GRb1 administration not only normalized Hrd1 expression at both the mRNA and protein levels, but also alleviated the ER stress response, Fas-related apoptosis, and other colitis symptoms. In intestinal cell line IEC-6, the expression of Hrd1 was significantly decreased by LPS treatment, but was normalized by GRb1 (200 µM). GRb1 alleviated LPS-induced ER stress and cell apoptosis in IEC-6 cells, and GRb1 action was inhibited by knockdown of Hrd1 using small interfering RNA. In summary, these results reveal a pathological role of Hrd1 in colitis, and provide a novel insight into alternative treatment of colitis using GRb1 activating Hrd1 signaling pathway.

Bridging "Office-Based Care" With the "Virtual Practice Care Model": Evolving Care for Chronic Kidney Disease Patients in the COVID-19 Pandemic-And Beyond.

Since the outbreak of the coronavirus epidemic, the "virtual" telemedicine has become a critical substitute for patient-provider interactions. However, virtual encounters often face challenges in the care of patients in high-risk categories such as chronic kidney disease (CKD) patients. In this study, we explore the patient's satisfaction and the practical effects of a newly established telemedicine program on CKD patients' care during the COVID-19 pandemic. Based on a prior version of an online patient care platform established in 2017, we developed a customized and improved online telemedicine program designed to specifically address the challenges emerging from the pandemic. This included an online, smart phone-based strategy for triage and medical care delivery and psychological support. We invited a total of 278 CKD patients to join the new platform during the pandemic. The subjects in group A were patients utilizing our old online CKD system and were historical users registered at least 3 months before the pandemic. A pilot survey interrogating medical and psychological conditions was conducted. Feedback on the program as well as a psychological assessment were collected after 1 month. In total, 181 patients showed active responses to the program, with 289 person-time medical consultations occurring during the study. The virtual care program provided a rapid triage for 17% (30 out of 181) patients, with timely referral to in-patient medical encounters for their worsening medical conditions or severe psychological problems. Nearly all patients (97.4%) believed the program was helpful. The number of symptoms (OR 1.309, 95%CI 1.113-1.541; P = 0.001) and being enrolled during the pandemic (OR 3.939, 95% CI 1.174-13.221; P = 0.026) were associated with high stress. During the follow-up, the high-stress CKD group at baseline showed a significant decrease in avoidance score (6.9 ± 4.7 vs. 9.8 ± 1.9, P = 0.015). In conclusion, during the pandemic, we established an online telemedicine care program for CKD patients that provides a rapid triage function, effective CKD disease management, and potentially essential psychological support.

Dual role of Ca2+-activated Cl- channel transmembrane member 16A in lipopolysaccharide-induced intestinal epithelial barrier dysfunction in vitro.

Dysfunction of intestinal epithelial Cl- currents and channels have previously been reported in inflammatory intestinal diseases. However, the expression and function of the newly identified Ca2+-activated Cl- channel transmembrane member 16A (TMEM16A) in the intestinal epithelium is unclear. In this study, we investigated the effects of TMEM16A on intestinal epithelial barrier function in vitro. Intestinal epithelial barrier dysfunction was modeled by lipopolysaccharide (LPS)-induced cell damage in intestinal epithelial IEC-6 cells and the effects of TMEM16A knockdown and overexpression on cell apoptosis and tight junctions were studied. Corresponding mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence analysis, respectively. TMEM16A expression was significantly increased by LPS, possibly via a process involving the transcription factor nuclear factor-κB and both Th1 and Th2 cytokines. Low- and high-dose LPS dysregulated tight junctions (high-myosin light-chain kinase expression) and cell apoptosis-dependent cell barrier dysfunction, respectively. TMEM16A aggravated cell barrier dysfunction in IEC-6 cells pretreated with low-dose LPS by activating ERK1/MLCK signaling pathways, but protected against cell barrier dysfunction by activating ERK/Bcl-2/Bax signaling pathways in IEC-6 cells pretreated with high-dose LPS. We concluded that TMEM16A played a dual role in LPS-induced epithelial dysfunction in vitro. The present results indicated the complex regulatory mechanisms and targeting of TMEM16A may provide potential treatment strategies for intestinal epithelial barrier damage, as well as forming the basis for future studies of the expression and function of TMEM16A in normal and inflammatory intestinal diseases in vivo.

Early-start and conventional-start peritoneal dialysis: a Chinese cohort study on outcome.

Background: Early-start peritoneal dialysis (PD) is an effective option for patients need unplanned dialysis. However, there are few studies on the long-term prognosis of early-start PD patients.Methods: In this retrospective study, 635 eligible patients from 1 March 1996 to 30 September 2016 were included, and divided into three groups according to the duration of break-in period: 3 days or less, 4-13 days and more than 14 days. Patients started PD within 2 weeks and after 2 weeks were defined as early-start and conventional-start, respectively. The primary outcome was all-cause mortality, and the secondary outcome measures were peritonitis free survival and technical survival. Mechanical and infectious complications in the first 180 days were also analyzed.Results: Early-start PD patients were more likely to have higher serum total carbon dioxide and creatinine levels and lower serum albumin, Kt/v, creatinine clearance (Ccr) and residual glomerular filtration rate (rGFR) levels at the start of PD. The median follow-up period was 30 months (interquartile range, 13-53 months). A worse survival was observed in the early-start group than that in the conventional-start group (p < 0.001), even adjustment for the covariates (HR 1.549, 95%CI 1.104-2.173, p = 0.011). In the subgroup analysis, in patients commencing PD after 2006 early-start and conventional-start PD patients had comparable survival. No differences were observed in the rate of infectious and mechanical complications, peritonitis-free survival and technique survival between early-start and conventional-start PD patients.Conclusions: Early-start PD could be a safe and effective strategy for patients needing unplanned dialysis initiation with the progress of technology on PD.

Immobilization of Horseradish Peroxidase on Multi-Armed Magnetic Graphene Oxide Composite: Improvement of Loading Amount and Catalytic Activity.

In this study, a novel type of multi-armed polymer (poyltehylene glycol, PEG) magnetic graphene oxide (GO) composite (GO@Fe3O4@6arm-PEG-NH2) has been synthesized as a support for immobilization of horseradish peroxidase (HRP) for the first time. The loading amount of HRP was relatively high (186.34 mg/g) due to the surface of carrier material containing a large amount of amino groups from 6arm-PEG-NH2, but degradation rate of phenols was also much higher (95.4%), which is attributed to the synergistic effect between the free HRP (45.4%) and the support material of GO@Fe3O4@6arm-PEG-NH2 (13.6%). Compared with the free enzyme, thermal, storage and operational stability of the immobilized HRP improved. The immobilized HRP still retained over 68.1% activity after being reused 8 times. These results suggest that the multi-armed magnetic composite has good application prospect for enzyme immobilization.