Primary microcephaly is caused by mutations in genes encoding centrosomal proteins including WDR62 and KIF2A. However, mechanisms underlying human microcephaly remain elusive. By creating mutant mice ...and human cerebral organoids, here we found that WDR62 deletion resulted in a reduction in the size of mouse brains and organoids due to the disruption of neural progenitor cells (NPCs), including outer radial glia (oRG). WDR62 ablation led to retarded cilium disassembly, long cilium, and delayed cell cycle progression leading to decreased proliferation and premature differentiation of NPCs. Mechanistically, WDR62 interacts with and promotes CEP170's localization to the basal body of primary cilium, where CEP170 recruits microtubule-depolymerizing factor KIF2A to disassemble cilium. WDR62 depletion reduced KIF2A's basal body localization, and enhanced KIF2A expression partially rescued deficits in cilium length and NPC proliferation. Thus, modeling microcephaly with cerebral organoids and mice reveals a WDR62-CEP170-KIF2A pathway promoting cilium disassembly, disruption of which contributes to microcephaly.
Effective hemostasis is vital to reduce the pain and mortality of patients, and the research and development of hemostatic materials are prerequisite for effective hemostasis. Chitosan (CS), with ...good biodegradability, biocompatibility and non-toxicity, has been widely applied in bio-medicine, the chemical industry, the food industry and cosmetics. The excellent hemostatic properties of CS have been extensively studied. As a result, chitosan-based composite hemostatic materials have been emerging. In this review, the hemostatic mechanism of chitosan is briefly discussed, and then the progress of research on chitosan-based composite hemostatic materials with multiple forms such as films, sponges, hydrogels, particles and fibers are introduced. Finally, future perspectives of chitosan-based composite hemostatic materials are given. The objective of this review is to provide a reference for further research and development of effective hemostatic materials.
Switchable materials play an invaluable role in signal processing and encryption of smart devices. The development of multifunctional materials that exhibit switching characteristics in multiple ...physical channels has attracted widespread attention. Now, two chiral thermochromic ferroelastic crystals (S‐CTA)2CuCl4 and (R‐CTA)2CuCl4 (CTA=3‐chloro‐2‐hydroxypropyltrimethylammonium) have been prepared with switchable properties in dielectricity, conductivity, second harmonic generation (SHG), piezoelectricity, ferroelasticity, chiral, and thermochromic properties. Compared with traditional phase‐transition materials with switching features, thermochromism brings additional spectral encryption possibilities for future information processing. To the best of our knowledge, this is the first chiral thermochromic ferroelastic that exhibits switching properties in seven physical channels. This work is expected to promote further exploration of multifunctional molecular switchable materials.
Seven switches: A pair of chiral thermochromic ferroelastics (R‐CTA)2CuCl4 and (S‐CTA)2CuCl4 (CTA=3‐chloro‐2‐hydroxypropyltrimethylammonium) exhibit switching properties in seven physical channels of dielectricity, conductivity, SHG, piezoelectric, ferroelastic, chiral, and thermochromic properties.
The recent introduction of thermally activated delayed fluorescence (TADF) emitters is regarded as an important breakthrough for the development of high efficiency organic light‐emitting devices ...(OLEDs). The planar D and A groups are generally used to construct TADF emitters for their rigid structure and large steric hindrance. In this work, it is shown that many frequently used nonaromatic (noncontinuous conjugation or without satisfying Hückel's rule) planar segments, such as 9,9‐dimethyl‐9,10‐dihydroacridine, are actually pseudoplanar segments and have two possible conformations–a planar form and a crooked form. Molecules constructed from pseudoplanar segments can thus have two corresponding conformations. Their existence can have significant impact on the performance of many TADF emitters. Two design strategies are presented for addressing the problem by either (1) increasing the rigidity of these groups to suppress its crooked form or (2) increasing the steric hindrance of the linked group to minimize energy of the emitters with the highly twisted form. Following these strategies, two new emitters are synthesized accordingly and successfully applied in OLEDs demonstrating high external quantum efficiencies (20.2% and 18.3%).
A schematic energy level diagram of (2‐(9,9‐dimethylacridin‐10(9H)‐yl) thianthrene‐5,5,10,10‐tetraoxide) shows that molecules constructed from pseudoplanar segments can have two corresponding conformations, which have significant impact on the performance of many thermally activated delayed fluorescence emitters. By either increasing the rigidity of these groups, or by increasing the steric hindrance of the linked group, the problem can be addressed.
Performance of traditional model-based control relies upon accurate modeling. In motion control of flexible systems, it is desirable to use the reduced-order model for ease of trajectory planning and ...pole placement, but its performance is constrained by modeling inaccuracies due to the existence of friction and multiple flexible modes. To improve the tracking performance, we have developed a data-based method for iterative tuning of the parameters in the reduced-order inverse model within a three-degree-of-freedom composite control structure. The proposed method solely makes use of the input-output data obtained during closed-loop experiments to fine-tune the inverse system model, and accurate system modeling is not required. Unbiasedness of the cost function gradient estimation is proven under reasonable assumptions of stochastic properties of the perturbations. Simulation and experiments are conducted to further illustrate the proposed method and show its practical appeals in industrial applications.
A novel molecular model of connecting electron‐donating (D) and electron‐withdrawing (A) moieties via a space‐enough and conjugation‐forbidden linkage (D‐Spacer‐A) is proposed to develop efficient ...non‐doped thermally activated delayed fluorescence (TADF) emitters. 10‐(4‐(4‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl) phenoxy) phenyl)‐9,9‐dimethyl‐9,10‐dihydroacridine (DMAC‐o‐TRZ) was designed and synthesized accordingly. As expected, it exhibits local excited properties in single‐molecule state as D‐Spacer‐A molecular backbone strongly suppress the intramolecular charge‐transfer (CT) transition. And intermolecular CT transition acted as the vital radiation channel for neat DMAC‐o‐TRZ film. As in return, the non‐doped device exhibits a remarkable maximum external quantum efficiency (EQE) of 14.7 %. These results prove the feasibility of D‐Spacer‐A molecules to develop intermolecular CT transition TADF emitters for efficient non‐doped OLEDs.
Non‐doped OLEDs: A novel molecular model of connecting electron‐donating (D) and electron‐withdrawing (A) moieties through a conjugation‐forbidden spacer is proposed to develop efficient thermally activated delayed fluorescence emitters for non‐doped organic light‐emitting diodes. The structure shows intermolecular charge‐transfer (CT) transitions as the major radiative channel and a suppressed effect of photoluminescence concentration quenching.
Brain aging is the most important risk factor for neurodegenerative disorders, and abnormal apoptosis is linked to neuronal dysfunction. Specifically, studies have found that exercise effectively ...inhibits hippocampal neuronal apoptosis, while the molecular mechanism remains unclear. In the present study, we investigated the impact of aerobic exercise on hippocampal neuronal apoptosis in aging mice and the potential involvement of DAPK1 and its downstream pathways based on recent data that DAPK1 may be associated with neuronal death in neurodegenerative diseases. Senescent mice were subjected to 8 weeks of Aerobic training. Following behavioral testing, hippocampal samples were examined histologically and biochemically to detect pathological changes, neuronal apoptosis, and mRNA and protein levels. We found that the exercise intervention improved spatial memory and alleviated neuronal apoptosis in the brain. Notably, exercise down‐regulated DAPK1 expression and inhibited Fas death receptor transactivation and the mitochondrial apoptotic pathway in the hippocampus. These results shed new light on the protective effect of regular exercise against brain aging though modulating the DAPK1 pathway.
Apoptotic cascades are triggered in the hippocampus of mice following D‐galactose induction, which can exacerbate histopathological deterioration and impair cognitive memory. Exercise is an effective approach for slowing the progression of aging, but the mechanism by which exercise inhibits aging‐associated neuronal apoptosis remains unclear. Interestingly, we demonstrated that aerobic exercise downregulated DAPK1 along with its downstream CDKN2A/REDD1/FoXO1 pathway and decreased FoXO1 nuclear transcription, which inhibited the FasL and mitochondria‐mediated apoptotic pathways.
A dual-drive H-gantry is commonly used in many industrial processes to meet the requirement of high-precision Cartesian motion. Unlike the rigid-linked gantry stage, the flexure-linked counterpart ...allows a small degree of rotation of the crossarm to prevent possible damages. However, by this design, the chattering of control signals and inappropriate stiffness of the flexure may induce the resonant modes of the gantry. Hence, to maintain the precision tracking of the midpoint position and the orientation of the gantry, as well as to minimize the vibration on the end effector, we seek the most suitable flexure stiffness and controller parameters by formulating a constrained linear-quadratic optimization problem. Since such a mechatronic design problem is not solvable via standard linear-quadratic regulator formulas, we convert it to a constrained projection gradient-based optimization problem, which can be efficiently solved by direct computation of projection gradient and line search of optimal step length. A fast convergence of parameters is achieved after first several iterations. Through a series of comparative experiments, the effectiveness of the proposed method is validated.
This paper provides an overview of the interrelationships between tourism and sustainability from a cross-disciplinary perspective. The current challenges and barriers in the tourism sustainability, ...such as high energy use, extensive water consumption and habitat destruction, are first reviewed. Then the key cross-disciplinary elements in sustainable tourism, including green energy, green transportation, green buildings, green infrastructure, green agriculture and smart technologies, are discussed. To overcome the challenges and barriers, a few implementation strategies on achieving sustainable tourism from the aspects of policy/regulation, institution, finance, technology and culture are proposed, along with the framework and details of a key performance indicator system. Finally, prospects of the potential for tourism to contribute to the transformative changes, e.g., a green economy system, are illustrated. This paper shine a light on issues of importance within sustainable tourism and encourage researchers from different disciplines in investigating the inter-relationships among community/culture, environment/ecology, and energy/water/food more broadly.
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•Challenges and barriers in tourism sector toward sustainability are illustrated.•A total of six key cross-disciplinary elements in sustainable tourism are proposed.•Strategies, framework and details of KPI system for green tourism are provided.•A case study of the Green Island, Taiwan toward a circular economy is presented.•Transformative changes in tourism such as water-energy-food nexus are described.
The development and malignancy of cancer cells are closely related to the changes of the epigenome. In this work, a mitochondria‐targeted rhenium(I) complex (DFX‐Re3), integrating the clinical iron ...chelating agent deferasirox (DFX), has been designed. By relocating iron to the mitochondria and changing the key metabolic species related to epigenetic modifications, DFX‐Re3 can elevate the methylation levels of histone, DNA, and RNA. As a consequence, DFX‐Re3 affects the events related to apoptosis, RNA polymerases, and T‐cell receptor signaling pathways. Finally, it is shown that DFX‐Re3 induces immunogenic apoptotic cell death and exhibits potent antitumor activity in vivo. This study provides a new approach for the design of novel epigenetic drugs that can recode the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis.
Reported here is a mitochondria‐targeted ReI complex, DFX‐Re3, that can relocate iron to the mitochondria and change the metabolites related to epigenetics. DFX‐Re3 can elevate the methylation levels of histone/DNA/RNA, affect RNA polymerase activities, and induce immunogenic apoptosis. This study provides a new approach to the design of epigenetic drugs for recoding the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis.
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