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Survival and stemness of bone marrow mesenchymal stem cells (BMSCs) in osteonecrotic areas are especially important in the treatment of early steroid-induced osteonecrosis of the femoral head (ONFH). We had previously used BMSCs to repair early steroid-induced ONFH, but the transplanted BMSCs underwent a great deal of stress-induced apoptosis and aging in the oxidative-stress (OS) microenvironment of the femoral-head necrotic area, which limited their efficacy. Our subsequent studies have shown that under OS, massive accumulation of damaged mitochondria in cells is an important factor leading to stress-induced apoptosis and senescence of BMSCs. The main reason for this accumulation is that OS leads to upregulation of protein 53 (P53), which inhibits mitochondrial translocation of Parkin and activation of Parkin’s E3 ubiquitin ligase, which decreases the level of mitophagy and leads to failure of cells to effectively remove damaged mitochondria. However, P53 downregulation can effectively reverse this process. Therefore, we upregulated Parkin and downregulated P53 in BMSCs. We found that this significantly enhanced mitophagy in BMSCs, decreased the accumulation of damaged mitochondria in cells, effectively resisted stress-induced BMSCs apoptosis and senescence, and improved the effect of BMSCs transplantation on early steroid-induced ONFH.

Several genetic risk factors for Alzheimer’s disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells 1 . However, the relationship between lipid metabolism in glia and Alzheimer’s disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer’s disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer’s disease having the APOE4/4 genotype. In human induced pluripotent stem cell-derived microglia, fibrillar Aβ induces ACSL1 expression, triglyceride synthesis and lipid droplet accumulation in an APOE-dependent manner. Additionally, conditioned media from lipid droplet-containing microglia lead to Tau phosphorylation and neurotoxicity in an APOE-dependent manner. Our findings suggest a link between genetic risk factors for Alzheimer’s disease with microglial lipid droplet accumulation and neurotoxic microglia-derived factors, potentially providing therapeutic strategies for Alzheimer’s disease. A microglial state, featuring lipid droplets and secretion of neurotoxic factors, is shown to be most prominent in people with Alzheimer’s disease who have the APOE4 genotype.

This paper presents a fusion algorithm based on the enhanced RRT* TEB algorithm. The enhanced RRT* algorithm is utilized for generating an optimal global path. Firstly, proposing an adaptive sampling function and extending node bias to accelerate global path generation and mitigate local optimality. Secondly, eliminating path redundancy to minimize path length. Thirdly, imposing constraints on the turning angle of the path to enhance path smoothness. Conducting kinematic modeling of the mobile robot and optimizing the TEB algorithm to align the trajectory with the mobile robot's kinematics. The integration of these two algorithms culminates in the development of a fusion algorithm. Simulation and experimental results demonstrate that, in contrast to the traditional RRT* algorithm, the enhanced RRT* algorithm achieves a 5.8% reduction in path length and a 62.5% decrease in the number of turning points. Utilizing the fusion algorithm for path planning, the mobile robot generates a superior, seamlessly smooth global path, adept at circumventing obstacles. Furthermore, the local trajectory meticulously conforms to the kinematic constraints of the mobile robot.

Legumes form symbiotic associations with either nitrogen-fixing bacteria or arbuscular mycorrhizal fungi. Formation of these two symbioses is regulated by a common set of signalling components that act downstream of recognition of rhizobia or mycorrhizae by host plants. Central to these pathways is the calcium and calmodulin-dependent protein kinase (CCaMK)–IPD3 complex which initiates nodule organogenesis following calcium oscillations in the host nucleus. However, downstream signalling events are not fully understood. Here we show that Medicago truncatula DELLA proteins, which are the central regulators of gibberellic acid signalling, positively regulate rhizobial symbiosis. Rhizobia colonization is impaired in della mutants and we provide evidence that DELLAs can promote CCaMK–IPD3 complex formation and increase the phosphorylation state of IPD3. DELLAs can also interact with NSP2–NSP1 and enhance the expression of Nod-factor-inducible genes in protoplasts. We show that DELLA is able to bridge a protein complex containing IPD3 and NSP2. Our results suggest a transcriptional framework for regulation of root nodule symbiosis. Symbiotic associations between legumes and nitrogen-fixing bacteria are regulated by a CCaMK-IPD3 protein complex which promotes nodule initiation. Here, Jin et al . propose that DELLA proteins positively regulate nodulation by enhancing phosphorylation of IPD3 and acting as a positive regulator of transcription.

Novel therapies for the treatment of early steroid-induced osteonecrosis of the femoral head (SONFH) are urgently needed in orthopedics. Transplantation of bone marrow mesenchymal stem cells (BMSCs) provides new strategies for treating this condition at the early stage. However, stress-induced apoptosis of BMSCs transplanted into the femoral head necrotic area limits the efficacy of BMSC transplantation. Inhibiting BMSC apoptosis is key to improving the efficacy of this procedure. In our previous studies, we confirmed that Parkinson disease protein 7 (PARK7) is active in antioxidant defense and can clear reactive oxygen species (ROS), protect the mitochondria, and impart resistance to stress-induced apoptosis in BMSCs. In this study, we investigated the mechanism driving this PARK7-mediated resistance to apoptosis in BMSCs. Our results indicate that PARK7 promoted the disintegration of nuclear factor (erythroid-derived 2)–like 2 (Nrf2)/Kelch-like echinacoside–associated protein 1 (Keap1) complex. The free Nrf2 then entered the nucleus and activated the genetic expression of manganese superoxide dismutase ( MnSOD ), catalase ( CAT ), glutathione peroxidase ( GPx ), and other antioxidant enzymes that clear excessive ROS, thereby protecting BMSCs from stress-induced apoptosis. To further explore whether PARK7-mediated resistance to stress-induced apoptosis could improve the efficacy of BMSC transplantation in early-stage SONFH, we transplanted BMSCs-overexpressing PARK7 into rats with early-stage SONFH. We then evaluated the survival of transplanted BMSCs and bone regeneration in the femoral head necrotic area of these rats. The results indicated that PARK7 promoted the survival of BMSCs in the osteonecrotic area and improved the transplantation efficacy of BMSCs on early-stage SONFH. This study provides new ideas and methods for resisting the stress-induced apoptosis of BMSCs and improving the transplantation effect of BMSCs on early-stage SONFH.

As flexible and wearable electronics play more and more important role in smart watches, smart glass and virtual reality, and the power supply to the wearable electronics have been revealed more attentions for long-term usage and continuous healthy monitoring. To overcome the challenge, flexible self-powered BTO-PVDF/PDMS piezoelectric-triboelectric electric hybrid generators (BPP-HNG) are developed to human gesture monitoring and human machine interaction (HMI) application without external power supply. BPP-HNG based on BTO-PVDF and PDMS films are prepared by sol–gel and spin-coating method. When the BTO content is 20 wt.%, BPP-HNG exhibits better electrical performance with an output voltage of 20.51 V. A real-time gesture monitoring system is designed and developed to human machine interaction, which is able to control the motion of robot finger through BPP-HNG. BPP-HNG could monitor and recognize various gestures in real time, enabling synchronization between the human hand and the robot’s hand. With the convergence of AI technology and big data, BPP-HNG based HMI technology is expected to realize the potential of smarter and more intuitive interactions.

Ferroptosis is an oxidative form of nonapoptotic cell death whose transcriptional regulation is poorly understood. Cap’n’collar (CNC) transcription factors including nuclear factor erythroid-2–related factor 1 (NFE2L1/NRF1) and NFE2L2 (NRF2) are important regulators of oxidative stress responses. NFE2L1 abundance and function are regulated posttranslationally by N-glycosylation. Functional maturation of NFE2L1 requires deglycosylation by cytosolic peptide:N-glycanase 1 (NGLY1). We find that NGLY1 and NFE2L1 work in a common pathway to enhance ferroptosis resistance, independent of NFE2L2, by promoting expression of the key antiferroptotic enzyme glutathione peroxidase 4 (GPX4). Enhanced ferroptosis sensitivity in NFE2L1-knockout cells can be reverted by expression of an NFE2L1 mutant containing eight asparagine-to-aspartate protein sequence substitutions, which mimic NGLY1-catalyzed protein sequence editing. These results suggest that ferroptosis sensitivity may be regulated by NGLY1-catalyzed NFE2L1 deglycosylation. These results highlight a role for the disease-associated NGLY1/NFE2L1 pathway in ferroptosis regulation.

Pre‐intercalation of metal ions into vanadium oxide is an effective strategy for optimizing the performance of rechargeable zinc‐ion battery (ZIB) cathodes. However, the battery long‐lifespan achievement and high‐capacity retention remain a challenge. Increasing the electronic conductivity while simultaneously prompting the cathode diffusion kinetics can improve ZIB electrochemical performance. Herein, N‐doped vanadium oxide (N‐(Zn,en)VO) via defect engineering is reported as cathode for aqueous ZIBs. Positron annihilation and electron paramagnetic resonance clearly indicate oxygen vacancies in the material. Density functional theory (DFT) calculations show that N‐doping and oxygen vacancies concurrently increase the electronic conductivity and accelerate the diffusion kinetics of zinc ions. Moreover, the presence of oxygen vacancies substantially increases the storage sites of zinc ions. Therefore, N‐(Zn,en)VO exhibits excellent electrochemical performance, including a peak capacity of 420.5 mA h g−1 at 0.05 A g−1, a high power density of more than 10 000 W kg−1 at 65.3 Wh kg−1, and a long cycle life at 5 A g−1 (4500 cycles without capacity decay). The methodology adopted in our study can be applied to other cathodic materials to improve their performance and extend their practical applications. N‐doping and oxygen vacancies were introduced on the VO framework by nitridation treatment, which reduced the interaction between the intercalated Zn2+ and the framework, accelerated the migration of Zn ions, and improved the electrochemical performance of the electrode. In addition, the formation mechanism of nitrogen doping and oxygen vacancies were systematically analyzed. The proposed N‐doping mechanism provides a reference for the construction of high‐performance cathode materials.

Lysosomes have many roles, including degrading macromolecules and signalling to the nucleus 1 . Lysosomal dysfunction occurs in various human conditions, such as common neurodegenerative diseases and monogenic lysosomal storage disorders (LSDs) 2 – 4 . For most LSDs, the causal genes have been identified but, in some, the function of the implicated gene is unknown, in part because lysosomes occupy a small fraction of the cellular volume so that changes in lysosomal contents are difficult to detect. Here we develop the LysoTag mouse for the tissue-specific isolation of intact lysosomes that are compatible with the multimodal profiling of their contents. We used the LysoTag mouse to study CLN3, a lysosomal transmembrane protein with an unknown function. In children, the loss of CLN3 causes juvenile neuronal ceroid lipofuscinosis (Batten disease), a lethal neurodegenerative LSD. Untargeted metabolite profiling of lysosomes from the brains of mice lacking CLN3 revealed a massive accumulation of glycerophosphodiesters (GPDs)—the end products of glycerophospholipid catabolism. GPDs also accumulate in the lysosomes of CLN3-deficient cultured cells and we show that CLN3 is required for their lysosomal egress. Loss of CLN3 also disrupts glycerophospholipid catabolism in the lysosome. Finally, we found elevated levels of glycerophosphoinositol in the cerebrospinal fluid of patients with Batten disease, suggesting the potential use of glycerophosphoinositol as a disease biomarker. Our results show that CLN3 is required for the lysosomal clearance of GPDs and reveal Batten disease as a neurodegenerative LSD with a defect in glycerophospholipid metabolism. The lysosomal transmembrane protein CLN3 is required for the lysosomal clearance of glycerophosphodiesters in mice and in human cells, suggesting that the loss of CLN3 causes Batten disease in children due to defects in glycerophospholipid metabolism.

With the rapid growth of railways in China, the focus has changed to the maintenance of large-scale rail structures. Multi-agent systems (MASs) based on wireless sensor network (WSNs) with soft multi-functional sensors (SMFS) are adopted cooperatively for the structural health monitoring of large-scale rail structures. An MAS framework with three layers, namely the sensing data acquisition layer, sensor data processing layer, and application layer, is built here for collaborative data collection and processing for a rail structure. WSN nodes with strain, temperature, and piezoelectric sensor units are developed for the continuous structural health monitoring of the rail structure. The feature data at different levels are extracted for the online monitoring of the rail structure. Experiments carried out at the Rail Transmit Base at East China Jiaotong University verify that the WSN nodes with SMFS are successfully assembled onto a 100-m-long track for damage detection. Based on the sensing data and feature data, a neural network data fusion agent (DFA) is applied to calculate the damage index value of the track for comprehensive decisions regarding rail damage. The use of WSNs with multi-functional sensors and intelligent algorithms is recommended for cooperative structural health monitoring in railways.