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Summary: We previously documented that individual microtubules in the axons of cultured juvenile rodent neurons consist of a labile domain and a stable domain and that experimental depletion of tau results in selective shortening and partial stabilization of the labile domain. After first confirming these findings in adult axons, we sought to understand the mechanism that accounts for the formation and maintenance of these microtubule domains. We found that fluorescent tau and MAP6 ectopically expressed in RFL-6 fibroblasts predominantly segregate on different microtubules or different domains on the same microtubule, with the tau-rich ones becoming more labile than in control cells and the MAP6-rich ones being more stable than in control cells. These and other experimental findings, which we studied further using computational modeling with tunable parameters, indicate that these two MAPs do not merely bind to pre-existing stable and labile domains but actually create stable and labile domains on microtubules.

Rosai-Dorfman-Destombes disease (RDD) is a rare histiocytic proliferative disorder, with primary scalp and intracranial involvement being particularly uncommon. The imaging features and clinical manifestations of RDD often overlap with other intracranial lesions, such as meningiomas, leading to misdiagnosis. This study presents a case of primary scalp and intracranial RDD, with a comprehensive analysis of its imaging, pathological, and intraoperative findings, alongside a review of the literature on central nervous system (CNS) RDD and its diagnostic and therapeutic advancements. Preoperative CT and MRI scans clearly depicted characteristic changes in the scalp and intracranial lesions. However, the preoperative assessment failed to fully recognize abnormalities in the skull base, leading to an incomplete initial understanding. During surgery, the dura mater and obstructed superior sagittal sinus were resected extensively, and the pathology confirmed RDD. Postoperative recovery was smooth, and no recurrence was observed during follow-up. This case emphasizes the importance of detailed imaging in the diagnosis and treatment of RDD, combining preoperative evaluation with intraoperative observations to reduce the risk of misdiagnosis and recurrence. Furthermore, the exploration of individualized treatment strategies and targeted therapies plays a crucial role in managing complex cases. This study offers valuable experience for the diagnosis and treatment of similar rare cases.

[INLINE:1] Fidgetin, a microtubule-severing enzyme, regulates neurite outgrowth, axonal regeneration, and cell migration by trimming off the labile domain of microtubule polymers. Because maintenance of the microtubule labile domain is essential for axon initiation, elongation, and navigation, it is of interest to determine whether augmenting the microtubule labile domain via depletion of fidgetin serves as a therapeutic approach to promote axonal regrowth in spinal cord injury. In this study, we constructed rat models of spinal cord injury and sciatic nerve injury. Compared with spinal cord injury, we found that expression level of tyrosinated microtubules in the labile portion of microtubules continuously increased, whereas fidgetin decreased after peripheral nerve injury. Depletion of fidgetin enhanced axon regeneration after spinal cord injury, whereas expression level of end binding protein 3 (EB3) markedly increased. Next, we performed RNA interference to knockdown EB3 or fidgetin. We found that deletion of EB3 did not change fidgetin expression. Conversely, deletion of fidgetin markedly increased expression of tyrosinated microtubules and EB3. Deletion of fidgetin increased the amount of EB3 at the end of neurites and thereby increased the level of tyrosinated microtubules. Finally, we deleted EB3 and overexpressed fidgetin. We found that fidgetin trimmed tyrosinated tubulins by interacting with EB3. When fidgetin was deleted, the labile portion of microtubules was elongated, and as a result the length of axons and number of axon branches were increased. These findings suggest that fidgetin can be used as a novel therapeutic target to promote axonal regeneration after spinal cord injury. Furthermore, they reveal an innovative mechanism by which fidgetin preferentially severs labile microtubules.

In order to study the influence of load change on the meshing characteristics of cycloid pinwheel of RV reducer, considering the modification of cycloid tooth profile, the three-dimensional model of cycloid pinwheel mechanism was established by UG. The changes of meshing tooth pairs and meshing stress of cycloid pinwheel in a meshing transmission cycle were analyzed by using the transient dynamics module of Ansys, and the simulation was compared with the theoretical contact stress. Results show that the overall trend of contact stress between simulation and theory is consistent, the number of meshing teeth and meshing stress of cycloid pinwheel show a periodic law, and increase with the increase of load. The change trend of contact stress and equivalent stress is opposite to the number of meshing teeth, the more the number of meshing teeth, the smaller the meshing stress. The equivalent stress of the needle tooth in the length direction increases with the increase of load, and the stress has a trend of uniform distribution, but the change is small. The finite element analysis has certain reference significance for the design, analysis and manufacture of RV reducer.

Approximately 30% of the veterans who fought in the 1991 Gulf War (GW) suffer from a disease called Gulf War Illness (GWI), which encompasses a constellation of symptoms including cognitive deficits. A coalescence of evidence indicates that GWI was caused by low-level exposure to organophosphate pesticides and nerve agents in combination with physical stressors of the battlefield. Until recently, progress on mechanisms and therapy had been limited to rodent-based models. Using peripheral blood mononuclear cells from veterans with or without GWI, we recently developed a bank of human induced pluripotent stem cells that can be differentiated into a variety of cellular fates. With these cells, we have now generated cerebral organoids, which are three-dimensional multicellular structures that resemble the human brain. We established organoid cultures from two GW veterans, one with GWI and one without. Immunohistochemical analyses indicate that these organoids, when treated with a GW toxicant regimen consisting of the organophosphate diisopropyl fluorophosphate (a sarin analog) and cortisol (to mimic battlefield stress), display multiple indicators consistent with cognitive deficits, including increased astrocytic reactivity, enhanced phosphorylation of tau proteins, decreased microtubule stability, and impaired neurogenesis. Interestingly, some of these phenotypes were more pronounced in the organoids derived from the veteran with GWI, potentially reflecting a stronger response to the toxicants in some individuals compared to others. These results suggest that veteran-derived human cerebral organoids not only can be used as an innovative human model to uncover the cellular responses to GW toxicants but can also serve as a platform for developing personalized medicine approaches for the veterans.

Engineered three-dimensional (3D) in vitro and ex vivo neural tissues, also known as “mini brains and spinal cords in a dish,” can be derived from different types of human stem cells via several differentiation protocols. In general, human mini brains are micro-scale physiological systems consisting of mixed populations of neural progenitor cells, glial cells, and neurons that may represent key features of human brain anatomy and function. To date, these specialized 3D tissue structures can be characterized into spheroids, organoids, assembloids, organ-on-a-chip and their various combinations based on generation procedures and cellular components. These 3D CNS models incorporate complex cell-cell interactions and play an essential role in bridging the gap between two-dimensional human neuroglial cultures and animal models. Indeed, they provide an innovative platform for disease modeling and therapeutic cell replacement, especially shedding light on the potential to realize personalized medicine for neurological disorders when combined with the revolutionary human induced pluripotent stem cell technology. In this review, we highlight human 3D CNS models developed from a variety of experimental strategies, emphasize their advances and remaining challenges, evaluate their state-of-the-art applications in recapitulating crucial phenotypic aspects of many CNS diseases, and discuss the role of contemporary technologies in the prospective improvement of their composition, consistency, complexity, and maturation.

The elimination of heat and smoke hazards during the polymer combustion process is still challenging. In this work, we created a thermal environment using a fire propagation apparatus (FPA) and studied the sustained effect of dry water coated on the surface of polymer materials after fire extinguishing. The tests indicated an effective burnback delay and the reduction of heat and smoke hazards. This approach significantly increased the ignition time and reduced the heat release rate and the smoke and carbon monoxide production rate compared to fuel without dry water coating. The radiation intensity influenced the sustained performance of dry water, i.e., the larger the radiation intensity, the worse sustained performance. The sustained performance was also improved by using an aqueous solution as inner material. A low mass fraction of the aqueous solution yielded an improved sustained performance in the initial combustion stage. Furthermore, the gelation of dry water with the inner aqueous solution could balance the structural strength and the thermal shielding performance. These results have implications for designing a technical program toward longer escape and rescue times for stranded persons and firefighters.

Hot compression tests for 2219/TiB2 Al-matrix composite were conducted on a Gleeble-3500 isothermal simulator in the temperature range of 300~500°C and strain rates of 0.01, 0.1, 1, 10s-1 to obtain true stress strain curves. The original Johnson-Cook model was calculated and used to describe the constitutive relationship of hot deformation behavior of this composite. After precision evaluation and analysis, a new modified Johnson-Cook model was proposed. Comparing with the original model, the new model has a lower absolute average relative error (AARE) of 6.4415% and a higher relative error (R) of 0.9852, which indicates better prediction precision. Meanwhile, to understand the intrinsic workability of this composite, processing map based on dynamic materials model was constructed. Two stable regions locating at 300~400°C&0.01~0.1s-1 and 420~500°C &0.01~1s-1 were identified by the processing map and the instable microstructure in the instability region validated the reliability of the processing map. Furthermore, the microstructure evolution was analyzed and the results revealed that the θ-phase reduced with the increasing temperature.

Mutations of the SPAST gene that encodes the microtubule-severing enzyme called spastin are the chief cause of Hereditary Spastic Paraplegia. Growing evidence indicates that pathogenic mutations functionally compromise the spastin protein and endow it with toxic gain-of-function properties. With each of these two factors potentially relevant to disease etiology, the present article discusses possible therapeutic strategies that may ameliorate symptoms in patients suffering from SPAST-based Hereditary Spastic Paraplegia, which is usually termed SPG4-HSP.

Water has unsurpassed capabilities in fire extinguishing. However, water scarcity is rapidly increasing in many regions and water shortage problems have led to find either new water resources or improve seawater treatment technologies. In this study, a new environment-friendly and high-efficiency powdered fire extinguishing agent with a core-shell structure is designed. The designed extinguishing agent is a colloidal powder with a 92% liquid content and is prepared through physical modification and high-speed shearing. Fumed silica is used for the external shell due to its chemical inertness, whereas seawater is used as the core due to its high extinguishing efficiency. Results show that the size of the prepared agent ranged between 100–200μm. The two fire extinguishing experiments of different scales demonstrate that the employing inorganic salts with seawater as the core can significantly increase the efficiency of the new powder in extinguishing gasoline and diesel fire compared with ultrafine and common ABC dry powders. The suppression mechanism of action is caused by the combined flame chemical and pyrolysis theories of the potassium compounds. This study would be of great theoretical significance and application value for improving the application scope of the seawater.