In diabetes mellitus, the polyol pathway is highly active and consumes approximately 30% glucose in the body. This pathway contains 2 reactions catalyzed by aldose reductase (AR) and sorbitol ...dehydrogenase, respectively. AR reduces glucose to sorbitol at the expense of NADPH, while sorbitol dehydrogenase converts sorbitol to fructose at the expense of NAD+, leading to NADH production. Consumption of NADPH, accumulation of sorbitol, and generation of fructose and NADH have all been implicated in the pathogenesis of diabetes and its complications. In this review, the roles of this pathway in NADH/NAD+ redox imbalance stress and oxidative stress in diabetes are highlighted. A potential intervention using nicotinamide riboside to restore redox balance as an approach to fighting diabetes is also discussed.
Reactive species produced in the cell during normal cellular metabolism can chemically react with cellular biomolecules such as nucleic acids, proteins, and lipids, thereby causing their oxidative ...modifications leading to alterations in their compositions and potential damage to their cellular activities. Fortunately, cells have evolved several antioxidant defense mechanisms (as metabolites, vitamins, and enzymes) to neutralize or mitigate the harmful effect of reactive species and/or their byproducts. Any perturbation in the balance in the level of antioxidants and the reactive species results in a physiological condition called “oxidative stress.” A catalase is one of the crucial antioxidant enzymes that mitigates oxidative stress to a considerable extent by destroying cellular hydrogen peroxide to produce water and oxygen. Deficiency or malfunction of catalase is postulated to be related to the pathogenesis of many age-associated degenerative diseases like diabetes mellitus, hypertension, anemia, vitiligo, Alzheimer’s disease, Parkinson’s disease, bipolar disorder, cancer, and schizophrenia. Therefore, efforts are being undertaken in many laboratories to explore its use as a potential drug for the treatment of such diseases. This paper describes the direct and indirect involvement of deficiency and/or modification of catalase in the pathogenesis of some important diseases such as diabetes mellitus, Alzheimer’s disease, Parkinson’s disease, vitiligo, and acatalasemia. Details on the efforts exploring the potential treatment of these diseases using a catalase as a protein therapeutic agent have also been described.
The discovery of two‐dimensional (2D) materials with unique electronic, superior optoelectronic, or intrinsic magnetic order has triggered worldwide interest in the fields of material science, ...condensed matter physics, and device physics. Vertically stacking 2D materials with distinct electronic and optical as well as magnetic properties enables the creation of a large variety of van der Waals heterostructures. The diverse properties of the vertical heterostructures open unprecedented opportunities for various kinds of device applications, e.g., vertical field‐effect transistors, ultrasensitive infrared photodetectors, spin‐filtering devices, and so on, which are inaccessible in conventional material heterostructures. Here, the current status of vertical heterostructure device applications in vertical transistors, infrared photodetectors, and spintronic memory/transistors is reviewed. The relevant challenges for achieving high‐performance devices are presented. An outlook into the future development of vertical heterostructure devices with integrated electronic and optoelectronic as well as spintronic functionalities is also provided.
The diverse properties of van der Waals heterostructures open unprecedented opportunities for various types of device applications inaccessible in conventional heterostructure materials. Research progress of vertical heterostructure device applications in vertical transistors, infrared photodetectors, and spintronic devices is reviewed, together with a discussion on the challenges and opportunities in the future development of multifunctional devices.
An extremely rare non‐Kramers holmium(III) single‐ion magnet (SIM) is reported to be stabilized in the pentagonal‐bipyramidal geometry by a phosphine oxide with a high energy barrier of 237(4) cm−1. ...The suppression of the quantum tunneling of magnetization (QTM) at zero field and the hyperfine structures originating from field‐induced QTMs can be observed even from the field‐dependent alternating‐current magnetic susceptibility in addition to single‐crystal hysteresis loops. These dramatic dynamics were attributed to the combination of the favorable crystal‐field environment and the hyperfine interactions arising from 165Ho (I=7/2) with a natural abundance of 100 %.
An extremely rare non‐Kramers holmium(III) single‐ion magnet is reported. The suppression of the quantum tunneling of magnetization at zero field and the hyperfine structures were observed in AC magnetic susceptibility measurements, and were attributed to the combination of a favorable crystal‐field environment and the hyperfine interactions arising from 165Ho (I=7/2) with a natural abundance of 100 %.
The kidneys are a vital organ that is vulnerable to both acute kidney injury (AKI) and chronic kidney disease (CKD) which can be caused by numerous risk factors such as ischemia, sepsis, drug ...toxicity and drug overdose, exposure to heavy metals, and diabetes. In spite of the advances in our understanding of the pathogenesis of AKI and CKD as well AKI transition to CKD, there is still no available therapeutics that can be used to combat kidney disease effectively, highlighting an urgent need to further study the pathological mechanisms underlying AKI, CKD, and AKI progression to CKD. In this regard, animal models of kidney disease are indispensable. This article reviews a widely used animal model of kidney disease, which is induced by folic acid (FA). While a low dose of FA is nutritionally beneficial, a high dose of FA is very toxic to the kidneys. Following a brief description of the procedure for disease induction by FA, major mechanisms of FA‐induced kidney injury are then reviewed, including oxidative stress, mitochondrial abnormalities such as impaired bioenergetics and mitophagy, ferroptosis, pyroptosis, and increased expression of fibroblast growth factor 23 (FGF23). Finally, application of this FA‐induced kidney disease model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given that this animal model is simple to create and is reproducible, it should remain useful for both studying the pathological mechanisms of kidney disease and identifying therapeutic targets to fight kidney disease.
Folic acid induced animal model of kidney disease was reviewed along with the mechanisms of the pathogenesis involved. This model can provide an important platform for the testing of a variety of therapeutic approaches that are designed to fight kidney disease including both acute kidney injury and chronic kidney disease.
Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by ...appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.
Polyporaceae is one of the most important families of Basidiomycota. Investigations on the species diversity, taxonomy and phylogeny of Polyporaceae in China are carried out. So far 217 species ...belonging to 42 genera are reported from China. Two new genera:
Amylosporia
gen. nov. and
Murinicarpus
gen. nov., twelve new species:
Coriolopsis dendriformis
sp. nov.,
C. hainanensis
sp. nov.,
Funalia cystidiata
sp. nov.,
Haploporus microsporus
sp. nov.,
Perenniporia citrinoalba
sp. nov.,
P. yinggelingensis
sp. nov.,
Picipes hainanensis
sp. nov.,
P. jiajinensis
sp. nov.,
P. pseudovarius
sp. nov.,
Trametes duplexa
sp. nov.,
T. ellipsoidea
sp. nov. and
T. stiptica
sp. nov., and six new combinations,
Amylosporia hattorii
comb. nov.,
Hornodermoporus latissimus
comb. nov.,
Murinicarpus subadustus
comb. nov.,
Picipes pumilus
comb. nov.,
Vanderbylia delavayi
comb. nov. and
Vanderbylia robiniophila
comb. nov., are proposed. All the species are described based on the Chinese collections. Keys to genera of Polyporaceae occurring in China and keys to species of each genus are provided. This monograph provides a revised classification of Polyporaceae in China according to the modern taxonomy. The phylogeny of Polyporaceae from China are reconstructed based on DNA sequences of multiple loci including the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), the small subunit nuclear ribosomal RNA gene (nSSU), the small subunit mitochondrial rRNA gene sequences (mtSSU), the translation elongation factor 1-α gene (TEF1), the β-tubulin gene (TBB1), the RNA polymerase II largest subunit (RPB1) and second largest subunit (RPB2) genes. In addition, full morphological descriptions, illustrations, color photographs, taxonomic notes, ecology and all the available sequences of Polyporaceae species found from China are provided.
Non-steroidal anti-inflammatory drugs (NSAIDs) which are widely used as pain relief medicines are causing increasing environmental concern due to their incomplete removal in wastewater treatment ...plant and potential toxicity on endocrine, kidney and reproduction in teleost fish. This study focused on the effects of widely used ibuprofen, diclofenac and paracetamol on the hatch and motor ability of early-stage zebrafish, by exposing embryos to the target chemicals at 5, 50 and 500 μg/L starting from 6 h postfertilization (hpf). A significant reduction in hatch rate at 55 hpf was caused by both ibuprofen (−63%) and diclofenac (−58%) at 500 μg/L. Exposure to high concentration of ibuprofen significantly decreased the spontaneous movement by 25%, and reduced the free swimming distance, duration and speed under dark condition by 41%, 29% and 30%, respectively. High concentration of diclofenac also caused 23% decrease in spontaneous movement, and reduced the swimming distance as well as active duration by 17% and 13% under light stimulation. In comparison, the exposure to paracetamol did not cause any notable effect. Among neuron related genes tested, the expression of neurog1 was down-regulated from ibuprofen and diclofenac exposure by 19% and 26%, while the expression of neurod1 was up-regulated only by ibuprofen (31%). These findings indicated that ibuprofen and diclofenac significantly affected embryo locomotivity and were potentially neurotoxic, thus posing threats to zebrafish development.
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•Behavior effects of 3 NSAIDs were assessed using zebrafish embryos.•Ibuprofen and diclofenac significantly suppressed embryo motion and hatching.•Both ibuprofen and diclofenac caused down-regulation of neurog1.•No significant effect from paracetamol exposure was observed.
Chemical ubiquitination is an effective approach for accessing structurally defined, atypical ubiquitin (Ub) chains that are difficult to prepare by other techniques. Herein, we describe a strategy ...that uses a readily accessible premade isopeptide‐linked 76‐mer (isoUb), which has an N‐terminal Cys and a C‐terminal hydrazide, as the key building block to assemble atypical Ub chains in a modular fashion. This method avoids the use of auxiliary‐modified Lys and instead employs the canonical and therefore more robust Cys‐based native chemical ligation technique. The efficiency and capacity of this isoUb‐based strategy is exemplified by the cost‐effective synthesis of several linkage‐ and length‐defined atypical Ub chains, including K27‐linked tetra‐Ub and K11/K48‐branched tri‐, tetra‐, penta‐, and hexa‐Ubs.
All together now: Chemical protein synthesis enabled the generation of homogeneous atypical ubiquitin (Ub) chains that are difficult to prepare by other approaches. A ligation method mediated by an isopeptide‐linked Ub isomer was developed to assemble the Ub chains. In this approach, a premade isopeptide‐linked 76‐mer (isoUb) bearing an N‐terminal Cys and a C‐terminal hydrazide is the key building block.
In this article, in order to optimize the dynamic performance of the permanent magnet synchronous motor (PMSM) speed regulation system, a nonlinear speed-control algorithm for the PMSM control ...systems using sliding-mode control is developed. First, a sliding-mode control method based on a new sliding-mode reaching law (NSMRL) is proposed. This NSMRL includes the system state variable and the power term of sliding surface function. In particular, the power term is bounded by the absolute value of the switching function, so that the reaching law can be expressed in two different forms during the reaching process. This method can not only effectively suppress the inherent chattering, but also increases the velocity of the system state reaching to the sliding-mode surface. Based on this new reaching law, a sliding-mode speed controller (SMSC) of PMSM is designed. Then, considering the large chattering phenomenon caused by high switching gain, an improved antidisturbance sliding-mode speed controller method, called SMSC + ESO method, is developed. This method introduces an extended state observer to observe the lumped disturbance and adds a feedforward compensation item based on the observed disturbances to the SMSC. Finally, simulation and experimental results both show the validity of the proposed control method.
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