Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Current treatment paradigm and survival outcomes among patients with newly diagnosed multiple myeloma in China:a retrospective multicenter study

Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).

A new autophagy-related nomogram and mechanism in multiple myeloma

Multiple myeloma(MM)is the second most common hematological tumor.It is characterized by high drug resistance,easy recurrence,and poor prognosis,and remains incurable.Various models or scoring modalities can be used to predict the survival prognosis of MM patients;however,these predictions are still not accurate enough.We have previously found that scorings related to bone marrow microenvironment metabolism can improve predictive efficacy.

ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells

Glioblastoma(GBM)is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment(TME).In this environment,myeloid cells,such as myeloid-derived suppressor cells(MDSCs),play a pivotal role in suppressing antitumor immunity.Lipometabolism is closely related to the function of myeloid cells.Here,our study reports that acetyl-CoA acetyltransferase 1(ACAT1),the key enzyme of fatty acid oxidation(FAO)and ketogenesis,is significantly downregulated in the MDSCs infiltrated in GBM patients.To investigate the effects of ACAT1 on myeloid cells,we generated mice with myeloid-specific(LyzM-cre)depletion of ACAT1.The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically.The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1(CXCLI)of macrophages(Mo).Overall,our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.

Energy management of hybrid electric propulsion system: Recent progress and a flying car perspective under three-dimensional transportation networks

The hybrid electric propulsion system(HEPS)holds clear potential to support the goal of sustainability in the automobile and aviation industry.As an important part of the three-dimensional transportation network,vehicles and aircraft using HEPSs have the advantages of high fuel economy,low emission,and low noise.To fulfill these advantages,the design of their energy management strategies(EMSs)is essential.This paper presents an in-depth review of EMSs for hybrid electric vehicles(HEVs)and hybrid electric aircraft.First,in view of the main challenges of current EMSs of HEVs,the referenced research is reviewed according to the solutions facing real-time implementation problems,variable driving conditions adaptability problems,and multi-objective optimization problems,respectively.Second,the existing research on the EMSs for hybrid electric aircraft is summarized according to the hybrid electric propulsion architectures.In addition,with the advance in propulsion technology and mechanical manufacturing in recent years,flying cars have gradually become a reality,further enriching the composition of the three-dimensional transportation network.And EMSs also play an essential role in the efficient operation of flying cars driven by HEPSs.Therefore,in the last part of this paper,the development status of flying cars and their future prospects are elaborated.By comprehensively summarizing the EMSs of HEPS for vehicles and aircraft,this review aims to provide guidance for the research on the EMSs for flying cars driven by HEPS and serve as the basis for knowledge transfer of relevant researchers.

Preparation of Ti-based Yb-doped SnO_(2)-RuO_(2) electrode and electrochemical oxidation treatment of coking wastewater

In this study,the Ti/SnO_(2)-RuO_(2) electrodes with different Yb contents were prepared by sol-gel method and thermal decomposition method,and the surface morphology and crystal structure of the electrodes were characterized by scanning electron microscopy(SEM),atomic force microscopy(AFM) and X-ray diffraction(XRD),the electrochemical properties of the electrodes were tested by linear sweep voltammetry(LSV) and cyclic voltammetry(CV).The electrochemical oxidation device was constructed with Yb-doped Ti/SnO_(2)-RuO_(2) electrode as the anode and titanium plate as the cathode,and the electrochemical oxidation effect and product changes of the anode on co king wastewater were investigated.The results show that the surface of the electrode is flat with high crystallinity of SnO_(2) and RuO_(2) crystals at1.5% Yb doping,and the LSV and CV curves indicate that the Yb doping of 1.5% increases the oxygen precipitation potential and electrocatalytic oxidation activity of the electrode.When the electrode with Yb doping of 1.5% is the anode with current density of 10 mA/cm^(2) electrochemical oxidation time of 30 min,the electrode can remove chemical oxygen demand(COD) up to 85.06%,total organic carbon(TOC) up to 60.59% and UV_(254) from 1.594 to 0.507 for coking wastewater.Gas chromatography(GC-MS),UV-vis and three-dimensional fluorescence results of coking wastewater before and after treatment show that large toxic substances in coking wastewater are degraded to low toxic organic substances,and most soluble organic substances are degraded and transformed.This study provides the possibility of basic research for the engineering practice of electrochemical oxidation for the treatment of coking wastewater.

Enhanced U(Ⅵ) bioreduction by alginate-immobilized uranium-reducing bacteria in the presence of carbon nanotubes and anthraquinone-2,6-disulfonate

Uranium-reducing bacteria were immobilized with sodium alginate, anthraquinone-2,6-disulfonate（AQDS）, and carbon nanotubes（CNTs）. The effects of different AQDS-CNTs contents, U（Ⅳ） concentrations, and metal ions on U（Ⅳ） reduction by immobilized beads were examined. Over 97.5% U（Ⅵ）（20 mg/L） was removed in 8 hr when the beads were added to 0.7% AQDS-CNTs, which was higher than that without AQDS-CNTs. This result may be attributed to the enhanced electron transfer by AQDS and CNTs. The reduction of U（Ⅵ） occurred at initial U（Ⅵ） concentrations of 10 to 100 mg/L and increased with increasing AQDS-CNT content from 0.1% to 1%. The presence of Fe（Ⅲ）, Cu（Ⅱ） and Mn（Ⅱ）slightly increased U（Ⅵ） reduction, whereas Cr（Ⅵ）, Ni（Ⅱ）, Pb（Ⅱ）, and Zn（Ⅱ） significantly inhibited U（Ⅵ） reduction. After eight successive incubation-washing cycles or 8 hr of retention time（HRT） for 48 hr of continuous operation, the removal efficiency of uranium was above 90% and 92%, respectively. The results indicate that the AQDS-CNT/AL/cell beads are suitable for the treatment of uranium-containing wastewaters.

Model-Based Double Closed-Loop Coordinated Control Strategy for the Electro-Mechanical Transmission System of Heavy Power-Split HEVs

The dual-mode electro-mechanical transmission(EMT)system is a crucial part of power-split hybrid electric vehicles(HEVs),especially for the heavy HEVs.To improve the precision of the system power distribution and the response speed of the electric power supply,a model-based double closed-loop coordinated control strategy is proposed.As the basis of the proposed control strategy,an EMT system model,particularly of an electrical system,is established first.The proposed control strategy includes the power distribution strategy,battery power closed-loop feedback control strategy,and motor coordinated control strategy.To verify the feasibility of the proposed control strategy,simulation and experiment are performed.The results indicate that the proposed control strategy can realize the expected power distribution by coordinating generators and motors and achieve rapid and stable electric power supply.

A path planning algorithm for autonomous flying vehicles in cross-countryenvironments with a novel TF-RRT^(*) method

Autonomous flying vehicles(AFVs)are promising future vehicles,which have high obstacle avoidance ability.To plan a feasible path in a wide range of cross-country environments for the AFV,a triggered forward optimal rapidly-exploring random tree(TF-RRT^(*))method is proposed.Firstly,an improved sampling and tree growth mechanism is built.Sampling and tree growth are allowed only in the forward region close to the target point,which significantly improves the planning speed;Secondly,the driving modes(ground-driving mode or air-driving mode)of the AFV are added to the sampling process as a planned state for uniform planning the driving path and driving mode;Thirdly,according to the dynamics and energy consumption models of the AFV,comprehensive indicators with energy consumption and efficiency are established for path optimal procedures,so as to select driving mode and plan driving path reasonably according to the demand.The proposed method is verified by simulations with an actual cross-country environment.Results show that the computation time is decreased by 71.08%compared with Informed-RRT^(*)algorithm,and the path length of the proposed method decreased by 13.01%compared with RRT^(*)-Connect algorithm.