In autoimmune diseases, a highly complex network comprising diverse cytokines and their receptors on immune cells drives the inflammatory response. A number of therapeutic antibodies targeting these ...disease-related molecules have been approved for the treatment of autoimmune diseases. Bispecific antibodies (bsAbs), with binding specificity for two different target molecules, have recently been developed for a range of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis, and tested in clinical trials. This review briefly describes the three main categories of bsAb structures developed for autoimmune diseases, including immunoglobulin G (IgG)-like, natural IgG, and tandem antibody fragment formats. The bsAbs developed and evaluated to date mainly target the depletion of T or B cells, the inhibition of T cell differentiation or activation, or the neutralization of proinflammatory cytokines. The clinical evaluation of bsAbs in autoimmune diseases is ongoing, with both successes (phase II trials of obexelimab in systemic lupus erythematosus) and failures (phase II trials of lutikizumab in osteoarthritis and romilkimab in idiopathic pulmonary fibrosis), and this review aims to provide a comprehensive, up-to-date summary of the clinical progress of bsAbs in this therapeutic area. Although many challenges remain, bsAbs offer new therapeutic options in the future direction of autoimmune disease treatments.
Aristotle’s visual theory plays a pivotal role in
De Anima
, he specifically analyzes three fundamental elements required for visual activities, namely, color, transparent substance, and light. Color ...moves and limits transparent substance, thereby transforming transparent substance from potentiality to actuality through light. However, there is a debate between Physicalism and Spiritualism as to the specific implementation of the visual activity. Through the intertwined mechanism, Aristotle’s theory of vision can be clarified. The visual activity is neither purely psychological nor purely physical, it is the “psycho-physical” intertwined mechanism. This is why Aristotle’s visual theory is closely related to contemporary visual psychology.
Recent surge of Convolutional Neural Networks (CNNs) has brought successes among various applications. However, these successes are accompanied by a significant increase in computational cost and the ...demand for computational resources, which critically hampers the utilization of complex CNNs on devices with limited computational power. In this work, we propose a feature representation based layer-wise pruning method that aims at reducing complex CNNs to more compact ones with equivalent performance. Different from previous parameter pruning methods that conduct connection-wise or filter-wise pruning based on weight information, our method determines redundant parameters by investigating the features learned in the convolutional layers and the pruning process is operated at a layer level. Experiments demonstrate that the proposed method is able to significantly reduce computational cost and the pruned models achieve equivalent or even better performance compared to the original models on various datasets.
The central nervous system is particularly susceptible to DNA repair deficiency, which renders a variety of neurodevelopmental and neurodegenerative disorders in humans. It is generally believed that ...DNA damage occurs upon repetitive replication and oxidative stress in highly proliferating neuroprogenitor cells (NPs), or due to high rates of metabolism and active neuronal activity in terminally differentiated neurons. DNA double‐stranded breaks (DSBs) and single‐stranded breaks (SSBs) constitute the most prevalent forms of DNA damage, which can result in neuronal apoptosis if unrepaired. Despite these notions, there are still gaps in our knowledge regarding the mechanism and specificity of DNA damage and repair in the neural development and the homeostasis of neural tissues. Recent studies have identified recurrent DSBs within neuronal long genes in NPs and ‘programmed’ SSBs in neuronal activity genes. However, the physiological function of these DNA breakages in the nervous system has not been so far explored. In this review, we summarise the recent advances in the field of DNA damage and DNA repair in neural development and neuropathies.
Programmed DNA breaks occur in neural progenitors during gene rearrangement. In neuronal cells, intrinsic and extrinsic signals can induce DNA breaks in promoters of response genes. Under DNA repair deficient conditions, these DNA damages accumulate and represent an etiological factor for human neurodevelopmental and neurodegenerative pathologies. Here, we summarise recent research on ‘programmed’ DNA breaks and their repair in these neural cells and imply their physiological functions in the nervous system.
In Xingxue cushu, Aleni devotes himself to elucidating Aristotle’s theory of perception as presented in De Anima and Parva Naturalia. The challenge in this endeavor lies in understanding the essence ...of Aristotle’s perception, with physicalism and spiritualism holding opposite positions. To reconcile this contradiction, some scholars approach it from the perspective of dualism and the impurity principle. Nevertheless, these interpretations fail to resolve the inherent dilemma of perception. This article employs the pattern of combination and separation to propose that Aleni’s interpretation of this dilemma is effective and clarifies the controversy. Perception encompasses both psychological and physical dimensions, and the two are based on each other in the process of actualization. Nonetheless, psychological and physical activities are separated in the definition. Influenced by Confucianism, Aleni associates human perception with morality, further emphasizing the necessity of definitional separation.
Unlike the positive philosophical thinking of friendship, the Homeric epics reveal the impact of friendly union namely community from disorder and conflicts. As the bond of communities, Homeric ...philotes is the reflection on the unions between family members, different kinds of companions, host and foreign guests. It covers almost all private and public friendly activity in those days. Although by reading Homer from the angle of social costume, the mainstream interpretation takes philotes as utilitarian relationship, in reality Homer epics defend friendly relationship and community mainly from morality and affections. The disinterestedness of morality and affections make pure friendly relation and union possible. By dealing with the friendly activity beyond secular communities with the same goal, the Homeric epics reveal the noblest and eternal altruistic inclination of humankind.
We present here the syntheses, crystal structures, and spin crossover (SCO) properties of a series of halogen‐functionalized cobalt(II) complexes, Co(Brphtpy)2(OTf)2 ⋅ DMF ⋅ 2H2O (1), ...Co(Brphtpy)2(HBS)2 ⋅ H2O (2), Co(Brphtpy)2(MQ)2 ⋅ 2MeCN ⋅ 3H2O (3) (Brphtpy=4′–(4‐Bromophenyl)–2,2′:6′,2′′‐terpyridine; OTf−=trifluoromethanesulfonate; HBS−=hydroxybenzenesulfonate dihydrate; MQ−=methyl orange). Variable‐temperature single‐crystal X‐ray analyses revealed mononuclear compounds of 1–3 consisted of Co(Brphtpy)22+ SCO active units and organosulfonate anions and no structural phase transformation happened in measured high‐low temperature. The packing structures of these complexes were tuned by varying organosulfonates. However, no notable supramolecular interactions can be found, in turn leading to gradual, incomplete, and non‐hysteretic SCO behaviors. Interestingly, the SCO behaviors of these three complexes were significantly modified after the removal of lattice solvents. Combined structural and magnetic investigations revealed the non‐cooperative supramolecular packing structures, guest internal pressure, and the small structural distortions of the SCO units should be responsible for the worse SCO properties of 1–3. The foregoing results show that to achieve high‐performance Co2+ SCO, both the weak interactions, internal pressure, and structural distortion should be considered during the design and construction of SCO complexes.
We reported the tunable spin‐crossover (SCO) behavior in a series of halogen‐functionalized cobalt(II) complexes constructed by the Co(Brphtpy)22+ SCO active units and various organosulfonates.
In recent years, research in the field of carbon nanomaterials (CNMs), such as fullerenes, expanded graphite (EG), carbon nanotubes (CNTs), graphene, and graphene oxide (GO), has been widely used in ...energy storage, electronics, catalysts, and biomaterials, as well as medical applications. Regarding energy storage, one of the most important research directions is the development of CNMs as carriers of energetic components by coating or encapsulation, thus forming safer advanced nanostructures with better performances. Moreover, some CNMs can also be functionalized to become energetic additives. This review article covers updated preparation methods for the aforementioned CNMs, with a more specific orientation towards the use of these nanomaterials in energetic compositions. The effects of these functionalized CNMs on thermal decomposition, ignition, combustion and the reactivity properties of energetic compositions are significant and are discussed in detail. It has been shown that the use of functionalized CNMs in energetic compositions greatly improves their combustion performances, thermal stability and sensitivity. In particular, functionalized fullerenes, CNTs and GO are the most appropriate candidate components in nanothermites, solid propellants and gas generators, due to their superior catalytic properties as well as facile preparation methods.
This review paper covers functionalized fullerene, CNTs and GO as components of nanothermites, high explosives, solid propellants and gas generators.
Glucose is the major precursor of lactose, which is synthesized in Golgi vesicles of mammary secretory alveolar epithelial cells during lactation. Glucose is taken up by mammary epithelial cells ...through a passive, facilitative process, which is driven by the downward glucose concentration gradient across the plasma membrane. This process is mediated by facilitative glucose transporters (GLUTs), of which there are 14 known isoforms. Mammary glands mainly express GLUT1 and GLUT8, and GLUT1 is the predominant isoform with a
K
m
of ~10 mM and transport activity for mannose and galactose in addition to glucose. Mammary glucose transport activity increases dramatically from the virgin state to the lactation state, with a concomitant increase in GLUT expression. The increased GLUT expression during lactogenesis is not stimulated by the accepted lactogenic hormones. New evidence indicates that a possible low oxygen tension resulting from increased metabolic rate and oxygen consumption may play a major role in stimulating glucose uptake and GLUT1 expression in mammary epithelial cells during lactogenesis. In addition to its primary presence on the plasma membrane, GLUT1 is also expressed on the Golgi membrane of mammary epithelial cells and is likely involved in facilitating the uptake of glucose and galactose to the site of lactose synthesis. Because lactose synthesis dictates milk volume, regulation of GLUT expression and trafficking represents potentially fruitful areas for further research in dairy production. In addition, this research will have pathological implications for the treatment of breast cancer because glucose uptake and GLUT expression are up-regulated in breast cancer cells to accommodate the increased glucose need.
Poly(ADP-ribosyl)ation (PARylation) is catalysed by poly(ADP-ribose) polymerases (PARPs, also known as ARTDs) and then rapidly removed by degrading enzymes. Poly(ADP-ribose) (PAR) is produced from ...PARylation and provides a delicate and spatiotemporal interaction scaffold for numerous target proteins. The PARylation system, consisting of PAR synthesizers and erasers and PAR itself and readers, plays diverse roles in the DNA damage response (DDR), DNA repair, transcription, replication, chromatin remodeling, metabolism, and cell death. Despite great efforts by scientists in biochemistry, cell and molecular biology, genetics, and pharmacology over the last five decades, the biology of PARPs and PARylation remains enigmatic. In this review, we summarize the current understanding of the biological function of PARP1 (ARTD1), the founding member of the PARP family, focusing on the inter-dependent or -independent nature of different functional domains of the PARP1 protein. We also discuss the readers of PAR, whose function may transduce signals and coordinate the cellular processes, which has recently emerged as a new research avenue for PARP biology. We aim to provide some perspective on how future research might disentangle the biology of PARylation by dissecting the structural and functional relationship of PARP1, a major effector of the PARPs family.
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