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Four distinct cytoplasmic structures generate and release specific vesicles, thus opening the way to intercellular communication
No full textIn all cells, generation and release of specific vesicles are the initial steps of back-and-forth intercellular communication. These processes are critical in normal physiology and pathophysiology. Vesicles have particular functions appropriate to their targets. When stimulated, they are released into the extracellular space. Four cytoplasmic membrane-bound structures generate their particular vesicles. Among these structures, multivesicular bodies (MVBs) can accumulate many small vesicles in their lumen; release occurs upon MVB exocytosis. Ectosomes are larger vesicles characterized by their responses and are generated directly and released independently from specific microdomains pre-established in the thickness of the plasma membrane. Most lysosomes do not generate vesicles. However, unique components of a minor form, the endo-lysosome, constitute the third class of structures that release a few vesicles by exocytosis with molecules and structures inducing changes in the extracellular environment. The autophagosome, the fourth structure, releases several heterogeneous vesicles by exocytosis with malformed bio-molecules, assembled structures, and damaged organelles. Interestingly, the frequent interaction of autophagosomes with MVBs and their exosomes contributes to the regulation and intensity of their action. The specificity and function of released vesicles depend on their membranes’ and luminal cargoes’ composition and dynamics. An ongoing investigation of the various vesicles reveals new properties regarding their generation, release, and resulting extracellular processes. The growth of information about structures and their vesicles progressively extends the knowledge base regarding cell communication and contributes to their clinical applications
Metal-nitrogen-carbon catalysts towards acidic ORR in PEMFC: fundamentals, durability challenges, and improvement strategies
No full textMetal-Nitrogen-Carbon (M-N-C) materials are the most promising Platinum-group-metal (PGM)-free catalysts in replacing the high-cost and scarce Pt catalysts in proton exchange membrane fuel cells (PEMFCs). However, while striking improvement of M-N-C catalysts has been reached in activity, the headache degradation problems hinder their real-world application. Herein, we present a comprehensive overview of the durability of the M-N-C catalyst for oxygen reaction reduction (ORR). The fundamental understanding and identification of the ORR performance of M-N-C catalysts are discussed. Meanwhile, the standard methods to evaluate and predict the ORR performance of the PGM-free catalysts are suggested. We mainly introduce the durability challenges of the M-N-C catalyst and explain the inactivation mechanism in detail. The proposed solution and useful strategies to alleviate catalyst degradation are systematically summarized to overcome the durability bottlenecks
Protein homeostasis in the aged and diseased heart
No full textProtein homeostasis, the balance between protein synthesis and degradation, requires the clearance of misfolded and aggregated proteins and is therefore considered to be an essential aspect of establishing a physiologically effective proteome. Aging alters this balance, termed “proteostasis”, resulting in the progressive accumulation of misfolded and aggregated proteins. Defective proteostasis leads to the functional deterioration of diverse regulatory processes during aging and is implicated in the etiology of multiple pathological conditions underlying a variety of neurodegenerative diseases and in age-dependent cardiovascular disease. Detergent-insoluble protein aggregates have been reported by us in both aged and hypertensive hearts. The protein constituents were found to overlap with protein aggregates seen in neurodegenerative diseases such as Alzheimer’s disease. Therefore, targeting these protein components of aggregates may be a promising therapeutic strategy for cardiovascular pathologies associated with aging, ischemia, and/or hypertension
UAV maneuver decision-making via deep reinforcement learning for short-range air combat
No full textThe unmanned aerial vehicle (UAV) has been applied in unmanned air combat because of its flexibility and practicality. The short-range air combat situation is rapidly changing, and the UAV has to make the autonomous maneuver decision as quickly as possible. In this paper, a type of short-range air combat maneuver decision method based on deep reinforcement learning is proposed. Firstly, the combat environment, including UAV motion model and the position and velocity relationships, is described. On this basic, the combat process is established. Secondly, some improved points based on proximal policy optimization (PPO) are proposed to enhance the maneuver decision-making ability. The gate recurrent unit (GRU) can help PPO make decisions with continuous timestep data. The actor network's input is the observation of UAV, however, the input of the critic network, named state, includes the blood values which cannot be observed directly. In addition, the action space with 15 basic actions and well-designed reward function are proposed to combine the air combat environment and PPO. In particular, the reward function is divided into dense reward, event reward and end-game reward to ensure the training feasibility. The training process is composed of three phases to shorten the training time. Finally, the designed maneuver decision method is verified through the ablation study and confrontment tests. The results show that the UAV with the proposed maneuver decision method can obtain an effective action policy to make a more flexible decision in air combat
The role of human milk fats in shaping neonatal development and the early life gut microbiota
No full textHuman breast milk (HBM) is the main source of nutrition for neonates across the critical early-life developmental period. The highest demand for energy is due to rapid neurophysiological expansion post-delivery, which is largely met by human milk lipids (HMLs). These HMLs also play a prebiotic role and potentially promote the growth of certain commensal bacteria, which, via HML digestion, supports the additional transfer of energy to the infant. In tandem, HMLs can also exert bactericidal effects against a variety of opportunistic pathogens, which contributes to overall colonisation resistance. Such interactions are pivotal for sustaining homeostatic relationships between microorganisms and their hosts. However, the underlying molecular mechanisms governing these interactions remain poorly understood. This review will explore the current research landscape with respect to HMLs, including compositional considerations and impact on the early life gut microbiota. Recent papers in this field will also be discussed, including a final perspective on current knowledge gaps and potential next research steps for these important but understudied breast milk components
Perspectives on future research directions in green manufacturing for discrete products
No full textWith the increasing concern due to climate change caused by a higher atmospheric concentration of CO2 and other greenhouse gases, reducing environmental impact is becoming more important for every part of society. Manufacturing is responsible for a significant amount of energy/material consumption and environmental burden and, therefore, has a great opportunity to reduce its impact through green manufacturing. Green manufacturing presents opportunities across the manufacturing enterprise to increase the efficient usage of energy and material resources. These opportunities include designing products to consume fewer materials and energy during manufacturing and use, incorporating more efficient manufacturing processes, streamlining and optimizing manufacturing schedules and plans, and circularizing products. The goal of this paper will be to provide a perspective from the authors on the opportunities that exist within green manufacturing for discrete products through a review of pertinent topics and future directions. The paper will focus on processes, manufacturing equipment, manufacturing systems, recovering value at a product’s end-of-life, and additional thoughts that include metrics and indicators, techno-economic assessment, and a discussion of efficiency and effectiveness. Key findings from this review include a need for social indicators and renewable energy considerations in scheduling and process planning, integrating Industry 4.0 into circular economy along with social and institutional dimensions, consistency in the ability to measure and conceptualize metrics and indicators, a detailed evaluation of the life cycle impacts and cost of Addit Manuf, and more human and environment-oriented considerations for smart manufacturing
What to do with patients with active infective endocarditis complicated by intracranial bleeding
No full textCerebral complications, especially intracranial hemorrhage (ICH), are critical determinants of the early outcomes of cardiac surgery for active infective endocarditis (AIE). Relevant society guidelines still recommend delaying cardiac surgery for AIE complicated by ICH for 4 weeks. Some early studies indicated that the mortality decreases when cardiac surgery for ICH is delayed. In contrast, some reported that surgical intervention should not be delayed if an early operation is indicated, even in patients with ICH. The current literature on early versus late surgery for AIE with ICH is conflicting. ICH is classified by its mechanism which includes primary intraparenchymal hemorrhage, hemorrhagic transformation of ischemic infarcts, and rupture of intracranial infectious aneurysms. Some reported that for AIE with a mycotic cerebral aneurysm, early cardiac surgery should be done after repair of the aneurysm, either surgically or endovascularly. Except for the rupture of mycotic aneurysm, primary intraparenchymal hemorrhage and hemorrhagic transformation of ischemic infarcts remain a critical and challenging dilemma. Modifying the cardiopulmonary bypass (CPB) strategy might be necessary to improve the surgical outcomes of AIE with ICH. Some studies reported that cardiac surgery using nafamostat mesylate as an alternative anticoagulant during CPB (NM-CPB) was performed successfully. The NM-CPB can be a useful option as an anticoagulant in critical situations of cardiac surgery with ICH. The timing of surgery should be decided on a case-by-case basis with multidisciplinary specialties including cardiac and neurological teams
A novel insight into the nature of modified low-density lipoproteins and their role in atherosclerosis
No full textAtherosclerosis plays a significant role in the development of cardiovascular diseases, the leading cause of death worldwide. Modification of low-density lipoproteins (LDLs) is a critical event in atherogenesis. Native LDL undergoes several modifications that can lead to the formation of atherogenic modified LDLs. LDL modifications change their physicochemical and biological properties. Possible modifications include changes in the lipoprotein particle’s structure, size, charge, and composition. Uptake and utilization of modified LDLs are impaired in cells. Macrophages take up modified LDLs that promote forming of foam cells, one of the critical cellular components of atherosclerotic lesions. Nevertheless, the direct role of each atherogenic LDL modification in atherogenesis remains uncertain. This review highlights LDL's most critical atherogenic modifications, including oxidized, enzyme-modified, non-oxidative, desialylated, glycated and carbamylated LDLs. Studying the role of each type of LDL modification will clarify the unknown elements of atherosclerosis progression and facilitate the development of effective methods for its diagnosis, treatment, and prevention
System for the safe deployment of minimally invasive pancreaticobiliary surgery in Japan
No full textThe Japanese healthcare system is characterized by universal coverage and free access. It is an excellent social system that allows everyone to receive advanced medical care at a low cost. Minimally invasive hepato-pancreato-biliary (HPB) surgery in Japan is now covered by insurance. However, after experiencing a series of serious medical accidents, Japan’s government requested a more advanced system to safely promote highly advanced surgery including laparoscopic HBP surgery. As a practical measure, the academic societies of HPB surgery established a new prospective registration system for all cases of minimally invasive HPB for highly advanced hepatobiliary and pancreatic surgery while utilizing the existing technical certification system. Under these systems, hepatobiliary and pancreatic surgeries in Japan are now being undertaken gradually but safely
Laser-induced direct graphene patterning: from formation mechanism to flexible applications
No full textLaser-induced graphene (LIG), which is directly fabricated by laser carbonization of polymers, has gained much attention in recent years since its first discovery in 2014. Specifically, featuring native porosity, good mechanical properties, and excellent electrical/electrochemical properties, it is considered a promising material for flexible electronic devices. Meantime, LIG can be processed in the atmosphere within a few seconds, thereby significantly reducing the fabrication cost of graphene. Facilitated by these features, this methodology has received great development with worldwide efforts in the following years, including the formation mechanism of LIG, the diversity of laser sources (from infrared laser to ultraviolet laser), the diversity of carbon sources (thermoset polymers, thermoplastic polymers, and natural polymers), and property modulation of LIG (porosity, electrical property, hydrophilic/hydrophobic property, electrochemical property), along with the broad applications of LIG in various flexible electronic devices. Here, the recent advances in the mechanism studies and preparation methods of LIG are comprehensively summarized. The various technologies for the modification of LIG are reviewed. A thorough overview of typical LIG-based flexible electronic devices is presented. Finally, the current challenges and future directions are discussed
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