In situ ligand-modulated activation of inert Ce(III/IV) into ozonation catalyst for efficient water treatment.

As a classic strategy to maximize catalytic activity, modulation of the electronic structure of central metal using organic ligands encounters great challenge in radical reactions exemplified by advanced oxidation processes (AOPs) due to operando destruction of employed ligands. Herein, we provide a paradigm achieving in situ ligand-modulated activation of the originally inert Ce(III/IV) for catalytic ozonation as a representative AOP widely applied in full-scale water treatment. Among the small-molecule carboxylates typically produced from pollutant degradation during ozonation, we find oxalate (OA) is a potent ligand to activate Ce(III/IV), inducing 11.5- and 5.8-fold elevation in rate constants of O3 decomposition and atrazine degradation, respectively. The Ce(III)-OA complex is proved the catalytic active species to boost pollutant degradation, while the catalytic ozonation unusually involves both •OH-dependent and •OH-independent pathways with comparable contributions. Both experiment and density functional theory calculation results show the pronounced electron donating effect of OA as evidenced by the substantial decreases in the charge residing on Ce, the ionization potential, and the Ce(III/IV) electrode potential, affords the activation of the Ce center for efficient ozonation. A comprehensive kinetic model involving 67 reactions is established to verify and elaborate the catalytic mechanism. Moreover, with in situ OA production, trace Ce3+ enables autocatalytic mineralization and codegradation of typical contaminants, which are not observed in case of Fe2+ or Cu2+. In addition, Ce3+ outperforms numerous state-of-the-art ozonation catalysts in terms of mass activity. This study sheds light on sustainable activation of the metal center harnessing operando ligands produced from the catalyzed reaction.

Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target.

Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.

The role of extracellular vesicle immune checkpoints in cancer.

Immune checkpoints (ICPs) play a crucial role in regulating the immune response. In the tumor, malignant cells can hijack the immunosuppressive effects of inhibitory ICPs to promote tumor progression. Extracellular vesicles (EVs) are produced by a variety of cells and contain bioactive molecules on their surface or within their lumen. The expression of ICPs has also been detected in EVs. In vitro and in vivo studies have shown that extracellular vesicle immune checkpoints (EV ICPs) have immunomodulatory effects and are involved in tumor immunity. EV ICPs isolated from the peripheral blood of cancer patients are closely associated with the tumor progression and the prognosis of cancer patients. Blocking inhibitory ICPs has been recognized as an effective strategy in cancer treatment. However, the efficacy of immune checkpoint inhibitors (ICIs) in cancer treatment is hindered by the emergence of therapeutic resistance, which limits their widespread use. Researchers have demonstrated that EV ICPs are correlated with clinical response to ICIs therapy and were involved in therapeutic resistance. Therefore, it is essential to investigate the immunomodulatory effects, underlying mechanisms, and clinical significance of EV ICPs in cancer. This review aims to comprehensively explore these aspects. We have provided a comprehensive description of the cellular origins, immunomodulatory effects, and clinical significance of EV ICPs in cancer, based on relevant studies.

PAQR3 facilitates the ferroptosis of diffuse large B-cell lymphoma via the regulation of LDLR-mediated PI3K/AKT pathway.

Progesterone and adiponectin receptor 3 (PAQR3) has been found to regulate tumor progression by mediating cell ferroptosis. However, whether PAQR3 mediates ferroptosis in diffuse large B-cell lymphoma (DLBCL) needs further investigation. The mRNA and protein levels of PAQR3 and low-density lipoprotein receptor (LDLR) were assessed by qRT-PCR and WB assays. Cell proliferation was detected by MTT assay and EdU assay. Shrunken mitochondria was counted under transmission electron microscope. Cell ferroptosis was evaluated by measuring the levels of malondialdehyde, reactive oxygen species, glutathione, Fe2+ , and the protein expression of ferroptosis-related markers. PAQR3 and LDLR interaction was confirmed by RIP assay and pull-down assay. Our study showed that PAQR3 was underexpressed, while LDLR was overexpressed in DLBCL tissues and cells. Functionally, PAQR3 overexpression or LDLR knockdown restrained DLBCL cell proliferation and enhanced ferroptosis. Mechanistically, PAQR3 reduced LDLR expression by inhibiting its mRNA stability. Meanwhile, LDLR overexpression reversed PAQR3-mediated the promoting on DLBCL cell ferroptosis, and LY294002 (PI3K/AKT inhibitor) eliminated the inhibiting effects of LDLR overexpression on DLBCL cell ferroptosis. Additionally, excessive PAQR3 reduced DLBCL tumor growth by enhancing tumor cell ferroptosis through LDLR-mediated PI3K/AKT pathway. In conclusion, our data suggested that PAQR3 restrained DLBCL progression by aggravating ferroptosis, which was achieved by inhibiting LDLR expression to repress PI3K/AKT pathway.

Reversible pH-Gated MXene Membranes with Ultrahigh Mono-/Divalent-Ion Selectivity.

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Investigating causal relationships between the gut microbiota and inflammatory skin diseases: A Mendelian randomization study.

BACKGROUND: Numerous inflammatory skin diseases are associated with the gut microbiota. Studies of the association between gut microbiota and inflammatory skin diseases have yielded conflicting results owing to confounding factors, and the causal relationship between them remains undetermined. METHODS: Two-sample Mendelian randomization (MR) was used to examine the association between gut microbiota and four common inflammatory skin diseases: acne, psoriasis, urticaria and atopic dermatitis. The summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium along with the summary statistics of the four diseases were obtained from the FinnGen consortium. Causal relationships were assessed using the inverse variance weighted (IVW), weighted median, MR-Egger and maximum likelihood methods, and several sensitivity analyses were performed to ensure the accuracy of the results. Finally, reverse and multivariable MR analyses were performed to verify the robustness of the results. RESULTS: We found causal associations of Bacteroidaceae [odds ratio (OR), 2.25; 95% confidence interval (CI), 1.48-3.42; pivw = 0.0001], Allisonella (OR, 1.42; 95% CI, 1.18-1.70; pivw = 0.0002) and Bacteroides (OR, 2.25; 95% CI, 1.48-3.42; pivw = 0.0001) with acne, the Eubacterium fissicatena group with psoriasis (OR, 1.22; 95% CI, 1.10-1.35; pivw = 0.0002) and Intestinibacter with urticaria (OR, 1.28; 95% CI, 1.13-1.45; pivw = 0.0001). These results were corrected for a false discovery rate. Sensitivity analyses were performed to validate the robustness of the associations and reverse MR confirmed that the results were not influenced by the reverse effect. CONCLUSION: Our study revealed that some gut microbiota are risk factors for inflammatory skin diseases, providing new information on potential therapeutic targets. Additionally, a possible association with the gut-skin axis was confirmed. Further research is required to elucidate the mechanisms underlying these relationships.

Long term co-application of biochar and fertilizer could increase soybean yield under continuous cropping: insights from photosynthetic physiology.

BACKGROUND: Photosynthesis is the key to crop yield. The effect of biochar on photosynthetic physiology and soybean yield under continuous cropping is unclear. We conducted a long-term field experiment to investigate the effects of co-application of biochar and fertilizer (BCAF) on these parameters. Five treatments were established: F2 (fertilizer), B1F1 (3 t hm-2 biochar plus fertilizer), B1F2 (3 t hm-2 biochar plus reduced fertilizer), B2F1 (6 t hm-2 biochar plus fertilizer), and B2F2 (6 t hm-2 biochar plus reduced fertilizer). RESULTS: BCAF increased chlorophyll and leaf area, enhancing soybean photosynthesis. The net photosynthetic rate (Pn ), transpiration rate (Tr ), stomatal conductance (Gs ), water use efficiency (WUE) and intercellular carbon dioxide (CO2 ) concentration (Ci ) were enhanced by BCAF. In addition, BCAF improved soybean photosystem II (PSII) photosynthetic performance, driving force, potential photochemical efficiency (Fv /F0 ), and quantum yield of electron transfer (φE0 ). Furthermore, BCAF enhanced the accumulation of photosynthetic products, such as soluble proteins, soluble sugars and sucrose content, resulting in higher leaf dry weight. Consequently, BCAF increased the soybean yield, with the highest increase of 41.54% in B2F1. The correlation analysis revealed positive relationships between soybean yield and chlorophyll, leaf area, maximal quantum yield of PSII (Fv /Fm ), electron transport flux per cross-section at t = 0 (ET0 /CS0 ), trapped energy flux per cross-section at t = 0 (TR0 /CS0 ), composite blade driving force (DFTotal ), and leaf dry weight. CONCLUSIONS: We demonstrated that long-term BCAF enhances soybean photosynthesis under continuous planting, reduces fertilizer use and increases yield. This study reveals a novel way and theory to sustainably increase soybean productivity. © 2023 Society of Chemical Industry.

Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets.

BACKGROUND: The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. METHODS: The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium. RESULTS: JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. CONCLUSIONS: The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis.

Redox-Induced In Situ Growth of MnO2 with Rich Oxygen Vacancies over Monolithic Copper Foam for Boosting Toluene Combustion.

Catalytic combustion has been known to be an effective technique in volatile organic compound (VOC) abatement. Developing monolithic catalysts with high activity at low temperatures is vital yet challenging in industrial applications. Herein, monolithic MnO2-Ov/CF catalysts were fabricated via the in situ growth of K2CuFe(CN)6 (CuFePBA, a family of metal-organic frames) over copper foam (CF) followed by a redox-etching route. The as-synthesized monolith MnO2-Ov-0.04/CF catalyst displays a superior low-temperature activity (T90% = 215 °C) and robust durability for toluene elimination even in the presence of 5 vol % water. Experimental results reveal that the CuFePBA template not only guides the in situ growth of δ-MnO2 with high loading over CF but also acts as a source of dopant to create more oxygen vacancies and weaken the strength of the Mn-O bond, which considerably improves the oxygen activation ability of δ-MnO2 and consequently boosts the low-temperature catalytic activity of the monolith MnO2-Ov-0.04/CF toward toluene oxidation. In addition, the reaction intermediate and proposed mechanism in the MnO2-Ov-0.04/CF mediated catalytic oxidation process were investigated. This study provides new insights into the development of highly active monolithic catalysts for the low-temperature oxidation of VOCs.

Colocalization of Gene Expression and DNA Methylation with Genetic Risk Variants Supports Functional Roles of MUC5B and DSP in Idiopathic Pulmonary Fibrosis.

Rationale: Common genetic variants have been associated with idiopathic pulmonary fibrosis (IPF). Objectives: To determine functional relevance of the 10 IPF-associated common genetic variants we previously identified. Methods: We performed expression quantitative trait loci (eQTL) and methylation quantitative trait loci (mQTL) mapping, followed by co-localization of eQTL and mQTL with genetic association signals and functional validation by luciferase reporter assays. Illumina multi-ethnic genotyping arrays, mRNA sequencing, and Illumina 850k methylation arrays were performed on lung tissue of participants with IPF (234 RNA and 345 DNA samples) and non-diseased controls (188 RNA and 202 DNA samples). Measurements and Main Results: Focusing on genetic variants within 10 IPF-associated genetic loci, we identified 27 eQTLs in controls and 24 eQTLs in cases (false-discovery-rate-adjusted P < 0.05). Among these signals, we identified associations of lead variants rs35705950 with expression of MUC5B and rs2076295 with expression of DSP in both cases and controls. mQTL analysis identified CpGs in gene bodies of MUC5B (cg17589883) and DSP (cg08964675) associated with the lead variants in these two loci. We also demonstrated strong co-localization of eQTL/mQTL and genetic signal in MUC5B (rs35705950) and DSP (rs2076295). Functional validation of the mQTL in MUC5B using luciferase reporter assays demonstrates that the CpG resides within a putative internal repressor element. Conclusions: We have established a relationship of the common IPF genetic risk variants rs35705950 and rs2076295 with respective changes in MUC5B and DSP expression and methylation. These results provide additional evidence that both MUC5B and DSP are involved in the etiology of IPF.

Neuromuscular Electrical Stimulation for Post-Stroke Dysphagia Treatment: A Systemic Evaluation and Meta-Analysis of Randomized Controlled Trials.

Neuromuscular electrical stimulation (NMES) is a novel treatment method that stimulates patients' swallowing functions. This systemic review was designed to evaluate the impact of NMES on dysphagia in stroke patients. Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched from the date of establishment to January 28th, 2022. Two investigators identified all included studies and compared the swallowing function after NMES treatment with traditional therapy (TT). The Cochrane risk bias assessment tool was utilized to analyze the quality of included studies. Research outcomes included Swallowing Quality of Life (SWAL-QoL), Penetration-Aspiration Scale (PAS), Functional Oral Intake Scale (FOIS), Dysphagia Outcomes and Severity Scale (DOSS), the Repeat Salivary Swallowing Test (RSST), and Water Swallowing Test (WST). We extracted the mean and standard deviation of specific outcomes at the baseline level and after the treatment in both NMES and TT groups for subsequent meta-analysis. 9 randomized controlled trials (RCTs) and quasi-RCTs were included, and remarkable differences were found between patients treated with or without NMES in respect of FOIS scores (SMD = 0.48; 95% CI 0.26-0.70, P < 0.0001), PAS scores (SMD = - 0.56; 95% CI 1.01-0.10, P = 0.02), and SWAL-QoL scores (SMD = 0.57; 95% CI 0.00-1.14, P = 0.05). No significant difference was manifested in WST, RSST, and DOSS (SMD: - 0.02; 95% CI  0.38-0.35, P = 0.93). Evidence suggests that NMES is more effective for post-stroke dysphagia patients than treatment without NMES.

Observation of the clinical features of dupilumab-associated facial erythema.

Introduction: Dupilumab is the first biologic agent used to clinically treat moderate and severe atopic dermatitis (AD) and is currently the only biologic agent used for this condition. Many studies have reported that moderate-to-severe AD was significantly improved after dupilumab injection, although head/neck dermatitis occurred with itching, flushing, and scaling. Moreover, because all the symptoms occur after dupilumab treatment, they are called "dupilumab facial redness (DFR)". Aim: To retrospectively analyse the clinical characteristics and treatment of facial erythema in patients with atopic dermatitis treated with dupilumab. Material and methods: The clinical data of patients with moderate-to-severe atopic dermatitis treated with dupilumab (600 mg for the first time, 300 mg every 2 weeks thereafter) in the department of dermatology from July 2020 to May 2022 were obtained. We described their characteristics and analysed their symptomatic treatment measures and efficacy. Results: Twenty-one patients with DFR were included. Most clinical manifestations were erythema and pruritus, which differed from the symptoms of typical moderate-to-severe AD. After treatment, drug withdrawal, and dressing change, the symptoms of 17 patients were effectively controlled or completely improved, while these of 4 did not improve. Conclusions: Although the mechanism of DFR is still unclear, symptomatic treatment is partially effective, and medication discontinuation and switching to Janus kinase inhibitors are acceptable for some patients.

PaIRKAT: A pathway integrated regression-based kernel association test with applications to metabolomics and COPD phenotypes.

High-throughput data such as metabolomics, genomics, transcriptomics, and proteomics have become familiar data types within the "-omics" family. For this work, we focus on subsets that interact with one another and represent these "pathways" as graphs. Observed pathways often have disjoint components, i.e., nodes or sets of nodes (metabolites, etc.) not connected to any other within the pathway, which notably lessens testing power. In this paper we propose the Pathway Integrated Regression-based Kernel Association Test (PaIRKAT), a new kernel machine regression method for incorporating known pathway information into the semi-parametric kernel regression framework. This work extends previous kernel machine approaches. This paper also contributes an application of a graph kernel regularization method for overcoming disconnected pathways. By incorporating a regularized or "smoothed" graph into a score test, PaIRKAT can provide more powerful tests for associations between biological pathways and phenotypes of interest and will be helpful in identifying novel pathways for targeted clinical research. We evaluate this method through several simulation studies and an application to real metabolomics data from the COPDGene study. Our simulation studies illustrate the robustness of this method to incorrect and incomplete pathway knowledge, and the real data analysis shows meaningful improvements of testing power in pathways. PaIRKAT was developed for application to metabolomic pathway data, but the techniques are easily generalizable to other data sources with a graph-like structure.

The breakdown of protein hydrogen bonding networks facilitates biotransformation of protein wastewaters during anaerobic digestion methanogenesis: Focus on protein structure and conformation.

The low methanogenic efficiency of protein wastewater during anaerobic digestion can be attributed to the hydrolysis rate-limiting caused by the complex native structure of protein. In this study, the characterization of secondary structure alterations of protein molecules under acid-base stress was investigated and the effect of structure and conformation alterations on the methanogenic efficiency of protein wastewater biotransformation was analyzed. The optimal methane yields were obtained for protein wastewater pretreated with acid and base at pH = 3 and pH = 12, which was 29.4% and 35.7% higher than that of the control group (without pretreatment), reaching 142.6 ± 4.0 mL/g protein and 149.6 ± 16.1 mL/g protein, respectively. The time economy evaluation showed that 6 h pretreatment time was scientific and reasonable whether pH = 3 or pH = 12, since the methane gain effect reached 74.4% and 82.2% longing with the anaerobic digestion proceeded to 120 h, respectively. Endogenous fluorescence characteristics illustrated that the microenvironment of protein molecules has changed regardless of acid or alkali pretreatment. The circular dichroism (CD) analysis revealed that only the content of α-helix in the secondary structure of the protein at pH = 12 decreased by 46.3%, while the contents of ß-sheet, ß-turn and unordered structure were 29.5 ± 0.8%, 18.9 ± 0.6% and 32.2 ± 1.3%, respectively. The increase in the composition of the unordered structure demonstrated an irreversible damage to the hydrogen bonding network in the protein. FTIR spectroscopy further confirmed that the stretching vibrations of CO in amide I led to the destruction of the hydrogen bonding network and the unfolding of the protein structure. Thus, the above work provides new insights into the anaerobic digestion of protein wastewater for methanogenic processes from the perspective of protein structure and conformational changes.

The initial attempt at home hemodialysis in mainland China.

BACKGROUND: Observational studies have shown home hemodialysis (HHD) to be associated with better survival than facility hemodialysis (HD) and peritoneal dialysis (PD). Patients on HHD have reported higher quality of life and independence. HHD is considered to be an economical way to manage end-stage kidney disease (ESKD). The coronavirus disease 2019 pandemic has had a significant impact on patients with ESKD. Patients on HHD may have an advantage over in-center HD patients because of a lower risk of exposure to infection. PARTICIPANTS AND METHODS: We enrolled HD patients from our dialysis center. We first established the HHD training center. The training center was approved by the Chinese government. Doctors, nurses and engineers train and assess patients separately. There are three forms of patient monitoring: home visits, internet remote monitoring, and outpatient services. Demographic and medical data included age, sex, blood pressure, and dialysis-related data. Laboratory tests were conducted in our central testing laboratory, including hemoglobin (Hgb), serum creatinine (Cr), urea nitrogen (BUN), uric acid (UA), albumin (Alb), calcium (Ca), phosphorus (P), parathyroid hormone (PTH), and brain natriuretic peptide (BNP) levels. RESULTS: Six patients who underwent regular dialysis in the HD center of our hospital were selected for HHD training. We enrolled 6 patients, including 4 males and 2 females. The mean age of the patients was 47.5 (34.7-55.7) years, and the mean dialysis age was 33.5 (11.2-41.5) months. After an average of 16.0 (11.2-25.5) months of training, Alb, P and BNP levels were improved compared with the baseline values. After training, three patients returned home to begin independent HD. During the follow-up, there were no serious adverse events leading to hospitalization or death, but there were several adverse events. They were solved quickly by extra home visits of the technicians or online by remote monitoring. During the follow-up time, the laboratory indicators of all the patients, including Hgb, Alb, Ca, P, PTH, BNP, and ß2-MG levels, remained stable before and after HHD treatment. CONCLUSION: HHD is feasible and safe for ESKD in China, but larger-scale and longer-term studies are needed for further confirmation.

Oriented UiO-67 Metal-Organic Framework Membrane with Fast and Selective Lithium-Ion Transport.

Metal-organic frameworks (MOFs) membranes with high pore density and tunable pore size down to the subnanoscale exhibit great potential in ion separation when appropriately designed and prepared. By a washing-assisted secondary growing method, a well intergrown UiO-67 membrane with preferential growth along the [022] direction was synthesized on a polyvinylpyrrolidone (PVP)-modified AAO substrate. Because of the oriented growth of UiO-67 nanocrystals, highly interconnected ion-transporting channels are created throughout the UiO-67/AAO membrane capable of achieving an ultrahigh Li+ permeance of 27.01 mol m-2 h-1 as well as very decent Li+ /Mg2+ selectivity of up to 159.4. Molecular dynamics simulations reveal that the high selectivity is associated with the large disparity of the transport energy barrier between Li+ and Mg2+ , which is caused by different extents of ion dehydration in unique bimodal and oriented membrane channels.

Reproducibility of mass spectrometry based metabolomics data.

BACKGROUND: Assessing the reproducibility of measurements is an important first step for improving the reliability of downstream analyses of high-throughput metabolomics experiments. We define a metabolite to be reproducible when it demonstrates consistency across replicate experiments. Similarly, metabolites which are not consistent across replicates can be labeled as irreproducible. In this work, we introduce and evaluate the use (Ma)ximum (R)ank (R)eproducibility (MaRR) to examine reproducibility in mass spectrometry-based metabolomics experiments. We examine reproducibility across technical or biological samples in three different mass spectrometry metabolomics (MS-Metabolomics) data sets. RESULTS: We apply MaRR, a nonparametric approach that detects the change from reproducible to irreproducible signals using a maximal rank statistic. The advantage of using MaRR over model-based methods that it does not make parametric assumptions on the underlying distributions or dependence structures of reproducible metabolites. Using three MS Metabolomics data sets generated in the multi-center Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) study, we applied the MaRR procedure after data processing to explore reproducibility across technical or biological samples. Under realistic settings of MS-Metabolomics data, the MaRR procedure effectively controls the False Discovery Rate (FDR) when there was a gradual reduction in correlation between replicate pairs for less highly ranked signals. Simulation studies also show that the MaRR procedure tends to have high power for detecting reproducible metabolites in most situations except for smaller values of proportion of reproducible metabolites. Bias (i.e., the difference between the estimated and the true value of reproducible signal proportions) values for simulations are also close to zero. The results reported from the real data show a higher level of reproducibility for technical replicates compared to biological replicates across all the three different datasets. In summary, we demonstrate that the MaRR procedure application can be adapted to various experimental designs, and that the nonparametric approach performs consistently well. CONCLUSIONS: This research was motivated by reproducibility, which has proven to be a major obstacle in the use of genomic findings to advance clinical practice. In this paper, we developed a data-driven approach to assess the reproducibility of MS-Metabolomics data sets. The methods described in this paper are implemented in the open-source R package marr, which is freely available from Bioconductor at http://bioconductor.org/packages/marr .

αKlotho protein has therapeutic activity in contrast-induced acute kidney injury by limiting NLRP3 inflammasome-mediated pyroptosis and promoting autophagy.

Contrast-induced acute kidney injury (CI-AKI) is a main cause of hospital-acquired renal failure. Nevertheless, limited measures have been shown to be effective for the treatment of CI-AKI. Here, we demonstrated that αKlotho, which is highly expressed in kidney, has therapeutic activity in CI-AKI. Our data showed that αKlotho expression levels were decreased both in the kidney and serum of CI-AKI mice. Administration of αKlotho protein protected the kidney and HK-2 cells against contrast-induced injury. Mechanistically, αKlotho reduced contrast-induced renal tubular cells pyroptosis by limiting NLRP3 inflammasome activation. Meanwhile, αKlotho up-regulated autophagy via inhibiting the AKT/mTOR pathway and decreased mitochondrial ROS level. Inhibition of autophagy blunted the suppression effect of αKlotho on NLRP3 inflammasome activation and cell pyroptosis in contrast-treated HK-2 cells. Taken together, our data suggest that αKlotho protein protects against CI-AKI through inhibiting NLRP3 inflammasome-mediated pyroptosis, which is likely by promoting autophagy. αKlotho may be a promising therapeutic strategy for CI-AKI.

Soft Particles Enable Fast and Selective Water Transport through Graphene Oxide Membranes.

The intercalation strategy is successfully applied in tuning the interlayer distance of 2D membranes for efficient desalination and ion sieving. However, it is difficult to pursue a intercalant that is few nanometers in size and suitable for further chemical modification . Here, for the first time, we report the intercalation of soft particles-polyacrylonitrile gel particles (PAN GPs) inside the graphene oxide (GO) membranes, which allows for a tunable interlayer distance via the deformation of soft particles. Furthermore, the base-induced hydrophobic/hydrophilic structure of PAN GPs facilitates the water diffusion through the GO membrane. A fast and selective water permeation was observed through separation Cu-EDTA2-from water, with the permeance of 4-13 times higher than the reported 2D membranes. Intercalation of soft particles represents a promising strategy to fabricate high-performance 2D membranes.