Aims
Angioimmunoblastic T‐cell lymphoma (AITL) is genetically characterized by TET2 and DNMT3A mutations occurring in haematopoietic progenitor cells, and late events (e.g. the RHOA‐G17V mutation) ...associated with malignant transformation. As TET2/DNMT3A‐mutated progenitor cells can differentiate into multilineage progenies and give rise to both AITL and myeloid neoplasms, they may also have the potential to lead to other metachronous/synchronous neoplasms. We report two cases showing parallel evolution of two distinct potentially neoplastic lymphoid proliferations from a common mutated haematopoietic progenitor cell population.
Methods and results
Both cases presented with generalized lymphadenopathy. In case 1 (a 67‐year‐old female), an initial lymph node (LN) biopsy was dismissed as reactive, but a repeat biopsy showed a nodal marginal zone lymphoma (NMZL)‐like proliferation with an increase in the number of T‐follicular helper (TFH) cells. Immunohistochemistry, and clonality and mutational analyses by targeted sequencing of both whole tissue sections and microdissected NMZL‐like lesions, demonstrated a clonal B‐cell proliferation that harboured the BRAF‐G469R mutation and shared TET2 and DNMT3A mutations with an underlying RHOA‐G17V‐mutant TFH proliferation. Review of the original LN biopsy showed histological and immunophenotypic features of AITL. In case 2 (a 66‐year‐old male), cytotoxic T‐cell lymphoma with an increase in the number of Epstein–Barr virus‐positive large B cells was diagnosed on initial biopsy. On review together with the relapsed biopsy, we identified an additional occult neoplastic TFH proliferation/smouldering AITL. Both T‐cell proliferations shared TET2 and DNMT3A mutations while RHOA‐G17V was confined to the smouldering AITL.
Conclusions
In addition to demonstrating diagnostic challenges, these cases expand the potential of clonal haematopoiesis in the development of different lineage neoplastic proliferations.
Two unique cases show parallel evolution of distinct lymphoid neoplasms from a common TET2/DNMT3A mutated haematopoietic progenitor. In case 1, an EBV‐negative clonal B‐cell proliferation mimicking nodal marginal zone B‐cell lymphoma (NMZL) obscured an underlying angioimmunoblastic T cell lymphoma (AITL). In case 2, a predominant CD8+ cytotoxic T‐cell proliferation/lymphoma concealed an occult neoplastic T‐helper cell proliferation/smouldering AITL.
A novel hybrid nanomaterial was fabricated by encapsulating ZrO2 nanoparticles into spherical polystyrene beads (MPS) covalently bound with charged sulfonate groups (−SO3 –). The resultant adsorbent, ...Zr–MPS, exhibited more preferential sorption toward Pb(II) than the simple equivalent mixture of MPS and ZrO2. Such observation might be ascribed to the presence of sulfonate groups of the polymeric host, which could enhance nano-ZrO2 dispersion and Pb(II) diffusion kinetics. To further elucidate the role of surface functional groups, we encapsulated nano-ZrO2 onto another two macroporous polystyrene with different surface groups (i.e., −N(CH3)3 +/–CH2Cl, respectively) and a conventional activated carbon. The three obtained nanocomposites were denoted as Zr–MPN, Zr–MPC, and Zr–GAC. The presence of −SO3 – and −N(CH3)3 + was more favorable for nano-ZrO2 dispersion than the neutral −CH2Cl, resulting in the sequence of sorption capacities as Zr–MPS > Zr–MPN > Zr–GAC > Zr–MPC. Column Pb(II) sorption by the four nanocomposites further demonstrated the excellent Pb(II) retention by Zr–MPS. Comparatively, Zr–MPN of well-dispersed nano-ZrO2 and high sorption capacities showed much faster breakthrough for Pb(II) sequestration than Zr–MPS, because the electrostatic repulsion of surface quaternary ammonium group of MPN and Pb(II) ion would result in a poor sorption kinetics. This study suggests that charged groups in the host resins improve the dispersion of embedded nanoparticles and enhance the reactivity and capacity for sorption of metal ions. Suitably charged functional groups in the hosts are crucial in the fabrication of efficient nanocomposites for the decontamination of water from toxic metals and other charged pollutants.
To select the optimum fertilizer application under specific irrigation levels and to provide a reliable fertigation system for tomato plants, an experiment was conducted by using a microporous ...membrane for water-fertilizer integration under non-pressure gravity. A compound fertilizer (N:P2O5:K2O, 18:7:20) was adopted for topdressing at four levels, 1290 kg/ha, 1140 kg/ha, 990 kg/ha, and 840 kg/ha, and the locally recommended level of 1875 kg/ha was used as the control to explore the effects of different fertilizer application rates on growth, nutrient distribution, quality, yield, and partial factor of productivity (PFP) in tomato. The new regime of microporous membrane water-fertilizer integration under non-pressure gravity irrigation reduced the fertilizer application rate while promoting plant growth in the early and intermediate stages. Except for the 990 kg/ha fertilizer treatment, yields per plant and per plot for each fertilizer application rate were higher than or equal to those of the control. The new regime could effectively improve PFP and reduce soil nutrient enrichment. Fertilizer at 840 kg/ha showed the optimum results by increasing PFP by 75.72% as compared to control. In conclusion, the fertilizer rate at 840 kg/ha has not only maintained the productivity of soil but also tomato growth and quality of fruit which makes the non-pressure gravity irrigation a potential and cost-effective way for fertilizer application.
•High fluorescence intensity, uniform particle size of CdS QDs were obtained by this green biosynthetic techenique.•2. E. coli is nontoxic, easy to culture and widely present in nature.•Antibiotic ...drug sensitivity test showed it is a new idea on green intracellular synthesis of QDs without risky impact of bacterial resistance on environment.
In the paper, a green and efficient biosynthetical technique was reported for preparing cadmium sulfide (CdS) quantum dots, in which Escherichia coli (E. coli) was chosen as a biomatrix. Fluorescence emission spectra and fluorescent microscopic photographs revealed that as-produced CdS quantum dots had an optimum fluorescence emission peak located at 470nm and emitted a blue-green fluorescence under ultraviolet excitation. After extracted from bacterial cells and located the nanocrystals’ foci in vivo, the CdS quantum dots showed a uniform size distribution by transmission electron microscope. Through the systematical investigation of the biosynthetic conditions, including culture medium replacement, input time point of cadmium source, working concentrations of raw inorganic ions, and co-cultured time spans of bacteria and metal ions in the bio-manufacture, the results revealed that CdS quantum dots with the strongest fluorescence emission were successfully prepared when E. coli cells were in stationary phase, with the replacement of culture medium and following the incubation with 1.0×10−3mol/L cadmium source for 2 days. Results of antimicrobial susceptibility testing indicated that the sensitivities to eight types of antibiotics of E. coli were barely changed before and after CdS quantum dots were prepared in the mild temperature environment, though a slight fall of antibiotic resistance could be observed, suggesting hinted the proposed technique of producing quantum dots is a promising environmentally low-risk protocol.
The blind pursuit of high yields via increased fertilizer inputs increases the environmental costs. Relay intercropping has advantages for yield, but a strategy for N management is urgently required ...to decrease N inputs without yield loss in maize-soybean relay intercropping systems (IMS). Experiments were conducted with three levels of N and three planting patterns, and dry matter accumulation, nitrogen uptake, nitrogen use efficiency (NUE), competition ratio (CR), system productivity index (SPI), land equivalent ratio (LER), and crop root distribution were investigated. Our results showed that the CR of soybean was greater than 1, and that the change in root distribution in space and time resulted in an interspecific facilitation in IMS. The maximum yield of maize under monoculture maize (MM) occurred with conventional nitrogen (CN), whereas under IMS, the maximum yield occurred with reduced nitrogen (RN). The yield of monoculture soybean (MS) and of soybean in IMS both reached a maximum under RN. The LER of IMS varied from 1.85 to 2.36, and the SPI peaked under RN. Additionally, the NUE of IMS increased by 103.7% under RN compared with that under CN. In conclusion, the separation of the root ecological niche contributed to a positive interspecific facilitation, which increased the land productivity. Thus, maize-soybean relay intercropping with reduced N input provides a very useful approach to increase land productivity and avert environmental pollution.
Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including ...Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins—occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression of inflammation-related blood–brain barrier disruption and endoplasmic reticulum stress-based apoptosis.
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•SAH could result in mitochondrial morphological changes, Drp1 translocation onto mitochondria and ROS increase.•Mdivi-1 may induce the expression of mitochondrial complex I to reduce SAH-induced oxidative stress.•Mdivi-1 may inhibit oxidative stress-induced NF-κB-dependent BBB disruption to attenuate brain edema in SAH.•Mdivi-1 protects neuron against apoptosis probably through the inhibition of the PERK/ eIF2α/ CHOP pathway.
Prevention of infarct scar thinning and dilatation and stimulation of scar contracture can prevent progressive heart failure. Since microRNA 145 (miR‐145) plays an important role in cardiac ...fibroblast response to wound healing and cardiac repair after an myocardial infarction (MI), using a miR‐145 knock‐out (KO) mouse model, we evaluated contribution of down‐regulation of miR‐145 to cardiac fibroblast and myofibroblast function during adverse cardiac remodelling. Cardiac function decreased more and the infarct size was larger in miR‐145 KO than that in WT mice after MI and this phenomenon was accompanied by a decrease in cardiac fibroblast‐to‐myofibroblast differentiation. Quantification of collagen I and α‐SMA protein levels as well as wound contraction revealed that transdifferentiation of cardiac fibroblasts into myofibroblasts was lower in KO than WT mice. In vitro restoration of miR‐145 induced more differentiation of fibroblasts to myofibroblasts and this effect involved the target genes Klf4 and myocardin. MiR‐145 contributes to infarct scar contraction in the heart and the absence of miR‐145 contributes to dysfunction of cardiac fibroblast, resulting in greater infarct thinning and dilatation. Augmentation of miR‐145 could be an attractive target to prevent adverse cardiac remodelling after MI by enhancing the phenotypic switch of cardiac fibroblasts to myofibroblasts.
The effect of micro-porous layer (MPL) on proton exchange membrane (PEM) fuel cell cold start is investigated experimentally with theoretical analysis. Under normal condition, the anode and cathode ...MPLs can improve the independency on inlet gas humidification on the corresponding side. For potentiostatic startup, the humidity independence enhanced by anode MPL improves the cell performance at around −7 °C. Cathode MPL can promote the water back diffusion and hinder the ice formation on the catalyst layer (CL) surface at low temperature (e.g. −10 °C). Besides, anode MPL also contributes to reducing the blockage tendency at very low temperature (e.g. −15 °C or lower). For galvanostatic startup, water electrolysis and carbon corrosion may occur which leads to the voltage reversal when the cell cannot achieve the desired current density, which may produce more waste heat. Low water content will aggravate the voltage reversal and carbon corrosion.
•MPL reduces humidification requirement on each side for normal operation.•Anode MPL improves cold start from −7 °C by improving membrane hydration.•Cathode MPL hinders the ice formation on CL surface at −10 °C.•Anode MPL reduces possibility of random ice blockage at very low temperature.•Water shortage aggravates carbon corrosion and voltage reversal by fuel starvation.
Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody‐positive neuromyelitis optica ...spectrum disorder (AQP4‐NMOSD), and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4‐NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune‐associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4‐NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)‐like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM‐like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4‐NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most‐updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4‐NMOSD/MOGAD. Treatment cautions including drug‐drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.
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