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Purpose: Autophagy is frequently observed in tissues during the aging process, yet the tissues most strongly correlated with autophagy during aging and the underlying regulatory mechanisms remain inadequately understood. The purpose of this study is to identify the tissues with the highest correlation between autophagy and aging, and to explore the functions and mechanisms of autophagy in the aging tissue microenvironment. Methods: Integrated bulk RNA-seq from over 7000 normal tissue samples, single-cell sequencing data from blood samples of different ages, more than 2000 acute myeloid leukemia (AML) bulk RNA-seq, and multiple sets of AML single-cell data. The datasets were analysed using various bioinformatic approaches. Results: Blood tissue exhibited the highest positive correlation between autophagy and aging among healthy tissues. Single-cell resolution analysis revealed that in aged blood, classical monocytes (C. monocytes) are most closely associated with elevated autophagy levels. Increased autophagy in these monocytes correlated with a higher proportion of C. monocytes, with hypoxia identified as a crucial contributing factor. In AML, a representative myeloid blood disease, enhanced autophagy was accompanied by an increased proportionof C. monocytes. High autophagy levels in monocytes are associated with pro-inflammatory gene upregulation and Reactive Oxygen Species (ROS) accumulation, contributing to tissue aging. Conclusion: This study revealed that autophagy is most strongly correlated with aging in blood tissue. Enhanced autophagy levels in C. monocytes demonstrate a positive correlation with increased secretion of pro-inflammatory factors and elevated production of ROS, which may contribute to a more rapid aging process. This discovery underscores the critical role of autophagy in blood aging and suggests potential therapeutic targets to mitigate aging-related health issues. [ABSTRACT FROM AUTHOR]

Ni-rich layered oxides (LiNixCoyMn1−x−yO2, x > 0.8, NCM) are technologically important cathode (i.e., positive electrode) materials for next-generation high-energy batteries. However, they face challenges in cycle stability and durability due to internal strain accumulation and particle fracture as the batteries cycle. Here we report a simple molten-salt-assisted synthesis route to introduce gradiently distributed pores into the polycrystalline NCM secondary particles. The gradient porous strategy creates void spaces to buffer the anisotropic volume change of the primary particles, effectively mitigating the intergranular fracture and limiting the impedance growth. It not only increases the maximum accessible capacity of the NCM cathodes but also greatly enhances their cycle stability in practical pouch-type batteries and all-solid-state-batteries. It further enables a high nickel, low cobalt cathode (LiNi0.96Co0.02Mn0.02O2) with a combination of high specific energy (941.2 Wh kg−1 based on cathode weight at 0.1 C and 25 °C, 1 C = 245 mA g−1) and high stability during cycling (80.5% capacity retention after 800 cycles at 1 C relative to that of the first cycle) and high-temperature storage (reversible capacity retention >95.5% after 42-day storage at 60 °C at the fully charged state) in pouch cells. The generation of cracks in polycrystalline Ni-rich layered lithium transition metal oxides presents numerous challenges for their use in batteries. Here, authors propose a gradiently distributed pores structure within the oxide secondary particles, reducing internal strain accumulation. [ABSTRACT FROM AUTHOR]

Solid polymer electrolytes (SPEs) based all-solid-state batteries (ASSBs) have attracted extensive attention as a promising candidate for next-generation energy storage systems. Typical ASSBs require high fabrication pressure to achieve high areal capacity, under which, however, SPEs struggle and risk damage or failure due to their low mechanical strength. There is also a lack of study on complex stress and strain SPEs experience during ASSB cell assembly processes. Here, ceramic solid electrolytes are selected as interlayers to address the stress–strain conditions during assembling. As a result, high areal capacity ASSBs with a LiCoO2 loading of 12 mg·cm−2 were assembled with SPE-based composite electrolytes. Around 200 cycles were carried out for these cells at a current density of 1 mA·cm−2 under room temperature. The capacity decay of the battery at 200 cycles is observed to be as low as 0.06% per cycle. This work identifies a critical issue for application of SPEs in ASSBs and provides a potential strategy for the design of SPE-based ASSBs with high specific energy and long cycle life. [ABSTRACT FROM AUTHOR]

Colour centres in diamond have emerged as a leading solid-state platform for advancing quantum technologies, satisfying the DiVincenzo criteria1 and recently achieving quantum advantage in secret key distribution2. Blueprint studies3–5 indicate that general-purpose quantum computing using local quantum communication networks will require millions of physical qubits to encode thousands of logical qubits, presenting an open scalability challenge. Here we introduce a modular quantum system-on-chip (QSoC) architecture that integrates thousands of individually addressable tin-vacancy spin qubits in two-dimensional arrays of quantum microchiplets into an application-specific integrated circuit designed for cryogenic control. We demonstrate crucial fabrication steps and architectural subcomponents, including QSoC transfer by means of a ‘lock-and-release’ method for large-scale heterogeneous integration, high-throughput spin-qubit calibration and spectral tuning, and efficient spin state preparation and measurement. This QSoC architecture supports full connectivity for quantum memory arrays by spectral tuning across spin–photon frequency channels. Design studies building on these measurements indicate further scaling potential by means of increased qubit density, larger QSoC active regions and optical networking across QSoC modules.A modular quantum system-on-chip architecture integrates thousands of individually addressable spin qubits in two-dimensional quantum microchiplet arrays into an integrated circuit designed for cryogenic control, supporting full connectivity for quantum memory arrays across spin–photon channels. [ABSTRACT FROM AUTHOR]

Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer. [ABSTRACT FROM AUTHOR]

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)–SNAP23–SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18–SNAP23–SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, SEC22B, and SNAP23, and promotes the lipid mixing of SNAREs-reconstituted adiposomes by promoting LD clustering. Knockdown of STX18 in mouse liver via AAV resulted in smaller liver and reduced LD size under high-fat diet conditions. All these results demonstrate a critical role of the SNARE complex STX18–SNAP23–SEC22B in LD fusion. [ABSTRACT FROM AUTHOR]

The multi-subunit homotypic fusion and vacuole protein sorting (HOPS) membrane-tethering complex is required for autophagosome-lysosome fusion in mammals, yet reconstituting the mammalian HOPS complex remains a challenge. Here we propose a "hook-up" model for mammalian HOPS complex assembly, which requires two HOPS sub-complexes docking on membranes via membrane-associated Rabs. We identify Rab39A as a key small GTPase that recruits HOPS onto autophagic vesicles. Proper pairing with Rab2 and Rab39A enables HOPS complex assembly between proteoliposomes for its tethering function, facilitating efficient membrane fusion. GTP loading of Rab39A is important for the recruitment of HOPS to autophagic membranes. Activation of Rab39A is catalyzed by C9orf72, a guanine exchange factor associated with amyotrophic lateral sclerosis and familial frontotemporal dementia. Constitutive activation of Rab39A can rescue autophagy defects caused by C9orf72 depletion. These results therefore reveal a crucial role for the C9orf72-Rab39A-HOPS axis in autophagosome-lysosome fusion. The HOPS complex mediates membrane tethering and autophagosome-lysosome fusion. Here, the authors biochemically reconstitute the mammalian HOPS in protoliposomes and propose a model of complex assembly that depends on Rab2 and Rab39A. [ABSTRACT FROM AUTHOR]

The vanishing point (VP) is particularly important road information, which provides an important judgment criterion for the autonomous driving system. Existing vanishing point detection methods lack speed and accuracy when dealing with real road environments. This paper proposes a fast vanishing point detection method based on row space features. By analyzing the row space features, clustering candidates for similar vanishing points in the row space are performed, and then motion vectors are screened for the vanishing points in the candidate lines. The experimental results show that the average error of the normalized Euclidean distance is 0.0023716 in driving scenes under various lighting conditions. The unique candidate row space greatly reduces the amount of calculation, making the real-time FPS up to 86. It can be concluded that the fast vanishing point detection proposed in this paper would be suitable for high-speed driving scenarios. [ABSTRACT FROM AUTHOR]

A new type of aptamer-functionalized pH-responsive polymer-modified magnetic nanoparticles (ApMNPs) is introduced for specific enrichment and sensitive determination of lactoferrin (Lf) in complex matrixes. In the construction, Fe3O4@3-(Triethoxysilyl)propylmethacrylate@poly(4-Vinyl-1, 3-dioxolan-2-one-acrylic acid) (Fe3O4@MPS@p(VEC-AA)) were synthesized as pH-responsive polymer-modified magnetic nanoparticles (pMNPs) through free radical polymerization to increase the tunable interaction. Lf-binding aptamers were conjugated onto pMNPs through the reaction of amino-group in aptamer and epoxide-group in VEC, innovatively applied to prepare Lf-ApMNPs. On the basis of the synergistic effect of specific affinity of aptamer on Lf and tunable hydrophobic/hydrophilic property of pH-responsive polymer, Lf-ApMNPs presented good selectivity toward Lf, excellent adsorption capacity (as high as 233.9 mg g−1), as well as good recoveries in the range 93.6–99.6% in Lf-related nutrition samples. Significantly, the introduction of pH-responsive monomer (AA) effectively regulated the adsorption–desorption process of Lf, with the function similar to a switch. Moreover, the good performances of Ct-ApMNPs toward α-Chymotrypsin showed that ApMNPs exhibited universality to other proteins through easily changing the binding aptamer, thereby offering a facile and efficient approach for specific enrichment and sensitive determination of targets in real biological samples. [ABSTRACT FROM AUTHOR]

Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as evidenced by TRAF3 lysosomal and cytoplasmic accumulation. Eliglustat blocked autophagy by altering glycosphingolipid composition whilst restoration of missing glycosphingolipids rescued autophagy markers and TRAF3 degradation thus restoring osteoclastogenesis in bone marrow cells from myeloma patients. This work delineates both the mechanism by which glucosylceramide synthase inhibition prevents autophagic degradation of TRAF3 to reduce osteoclastogenesis as well as highlighting the clinical translational potential of eliglustat for the treatment of myeloma bone disease. Here, the authors show that the glycosylceramide synthesis inhibitor and FDA approved drug Eliglustat inhibits autophagic degradation of TRAF3 which is a key step for osteoclast differentiation and thereby improves myeloma bone lesions. [ABSTRACT FROM AUTHOR]

Urban lakes provide important ecological services to local communities, such as flood mitigation, biodiversity, and recreation. With rapid urbanization, urban lakes are significantly affected by socio-economic development and urgently need attention. Yet there is still a lack of datasets that include tiny urban lakes on a global or national scale. This study aims to produce a high-resolution circa-2020 map of urban lakes (≥0.001 km2) in China. The 10-m-resolution Sentinel-2 imagery and a simple but robust water extraction method was used to generate waterbodies. The accuracy of this national-scale dataset was evaluated by comparing it with manually sampled urban units, with the average accuracy of 81.85% in area and 93.35% in count. The database totally inventories 1.11 × 106 urban lakes in China, with a net area of ~2.13 × 103 km2. Overall, the spatial distribution of urban lakes in China showed strongly heterogeneous characteristics. This dataset will enhance our understanding of the distribution pattern of China's urban lakes and contribute to better ecological and environmental management as well as sustainable urban development planning. [ABSTRACT FROM AUTHOR]

Owing to the distinctive and designable properties of high-entropy alloys (HEAs), many researchers have been engrossed in studying them. The CrFeNiNbx (x is the molar ratio; x = 0.4, 0.5, 0.6, 0.7, 0.8) alloys were prepared using vacuum arc melting furnace equipment to study the impact of Nb content on microstructure, processing performance, and corrosion resistance. Laves primary phase and eutectic structure phase were obtained. And the area of the Laves primary structure, which was rich in Nb, was amplified when the alloy's percentage of Nb was supplemented. The Nb4 alloy (x = 0.4) exhibited a range of satisfactory mechanical properties, including a hardness of 422.3 HV, a compressive stress of 2355 MPa, and a compressive strain of 26.33%. Cracks formed around the Laves phase during electrochemical corrosion experimentation, and the alloy passivation film's breakdown potential was approximately 1.0 V. [ABSTRACT FROM AUTHOR]

Single-crystalline nickel-rich cathodes are a rising candidate with great potential for high-energy lithium-ion batteries due to their superior structural and chemical robustness in comparison with polycrystalline counterparts. Within the single-crystalline cathode materials, the lattice strain and defects have significant impacts on the intercalation chemistry and, therefore, play a key role in determining the macroscopic electrochemical performance. Guided by our predictive theoretical model, we have systematically evaluated the effectiveness of regaining lost capacity by modulating the lattice deformation via an energy-efficient thermal treatment at different chemical states. We demonstrate that the lattice structure recoverability is highly dependent on both the cathode composition and the state of charge, providing clues to relieving the fatigued cathode crystal for sustainable lithium-ion batteries. The lattice strain and defects in layered oxides is critical to the intercalation chemistry and battery performance. Here, the authors demonstrate a thermal-healing of lattice defects in single-crystalline cathodes caused by the thermal-induced release of lattice strain and the structure ordering. [ABSTRACT FROM AUTHOR]

The inhibition effect of tert-butyl alcohol (TBA), identified as the OH radical inhibitor, on the TiO nano assays (TNA) photoelectrocatalytic oxidation of different organics such as glucose and phthalate was reported. The adsorption performance of these organics on the TNA photoelectrode was investigated by using the instantaneous photocurrent value, and the degradation property was examined by using the exhausted reaction. The results showed that glucose exhibited the poor adsorption and easy degradation performance, phthalate showed the strong adsorption and hard-degradation, but TBA showed the weak adsorption and was the most difficult to be degraded. The degradation of both glucose and phthalate could be inhibited evidently by TBA. But the effect on glucose was more obvious. The different inhibition effects of TBA on different organics could be attributed to the differences in the adsorption and the degradation property. For instance, phthalate of the strong adsorption property could avoid from the capture of OH radicals by TBA in TNA photoelectrocatalytic process. [ABSTRACT FROM AUTHOR]

Carbon dioxide (CO) enrichment and increased nitrogen (N) deposition can change microbial activity and dissolved organic carbon (DOC) turnover, consequently affecting carbon sequestration in soils. However, we do not have much available information on the relationship between soil DOC and microbial activity under CO enrichment and N addition in semi-arid agroecosystems. Using free air CO enrichment (FACE), soybean and winter wheat were grown in the field under ambient CO (350 μmol mol) and elevated CO (550 μmol mol) conditions subjected to two N fertilizer regimes (132 and 306 kg N ha year). Rhizosphere soils and bulk soils at three depths, 0-10, 10-20 and 20-40 cm, were collected to determine water extractable organic matter (WEOM) characteristics with fluorescence spectroscopy and parallel factor analyses of excitation/emission matrix, as well as five extracellular enzymes activities. All significant effects were observed in the topsoil (0-10 cm): elevated CO decreased water extractable organic carbon concentration of the rhizosphere soils and bulk soils by 8.5 and 10.1 %, respectively. Furthermore, elevated CO changed the composition and structure of soil WEOM by increasing the plant- and microbial-derived components in the rhizosphere and solubilizing soil organic matter (SOM). The activities of β-1,4-glucosidase, cellobiohydrolase, phenol oxidase, and peroxidase were stimulated by elevated CO in the rhizosphere soils and bulk soils. Our findings suggest that the stimulation of microbial activity elicited by elevated CO increased the turnover of labile WEOM and the solubilization of SOM in the topsoils, which could be adverse to the accumulation and stability of soil carbon in the semi-arid agroecosystems in northern China. [ABSTRACT FROM AUTHOR]