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From the mechanical perspectives, the influence of point defects is generally considered at high temperature, especially when the creep deformation dominates. Here, we show the stress-induced reversible oxygen vacancy migration in CuO nanowires at room temperature, causing the unanticipated anelastic deformation. The anelastic strain is associated with the nucleation of oxygen-deficient CuO x phase, which gradually transforms back to CuO after stress releasing, leading to the gradual recovery of the nanowire shape. Detailed analysis reveals an oxygen deficient metastable CuO x phase that has been overlooked in the literatures. Both theoretical and experimental investigations faithfully predict the oxygen vacancy diffusion pathways in CuO. Our finding facilitates a better understanding of the complicated mechanical behaviors in materials, which could also be relevant across multiple scientific disciplines, such as high-temperature superconductivity and solid-state chemistry in Cu-O compounds, etc. The effect of point defects on mechanical behaviour of materials is generally considered at high temperatures. This work reports a reversible stress-induced migration of point defects during anelastic deformation in CuO nanowires at room temperature resulting from heterogeneous strain distribution.

Ultrafast electron microscopy (UEM) has found widespread applications in physics, chemistry, and materials science, enabling real-space imaging of dynamics on ultrafast timescales. Recent advances have pushed the temporal resolution of UEM into the attosecond regime, enabling the attomicroscopy technique to directly visualize electron motion. In this work, we extend the capabilities of this powerful imaging tool to investigate ultrafast electron dynamics in a biological system by imaging and controlling light induced electronic and chemical changes in the conductive network of multicellular cable bacteria. Using electron energy loss spectroscopy (EELS), we first observed a laser induced increase in -electron density, accompanied by spectral peak broadening and a blueshift features indicative of enhanced conductivity and structural modification. We also traced the effect of ultrafast laser pumping on bulk plasmon electron oscillations by monitoring changes in the plasmon like resonance peak. Additionally, we visualized laser induced chemical structural changes in cable bacteria in real space. The imaging results revealed carbon enrichment alongside a depletion of nitrogen and oxygen, highlighting the controllability of chemical dynamics. Moreover, time resolved EELS measurements further revealed a picosecond scale decay and recovery of both -electron and plasmonic features, attributed to electron phonon coupling. In addition to shedding light on the mechanism of electron motion in cable bacteria, these findings demonstrate ultrafast modulation and switching of conductivity, underscoring their potential as bio-optoelectronic components operating on ultrafast timescales.

The emergence of large-scale genomic, chemical and pharmacological data provides new opportunities for drug discovery and repositioning. In this work, we develop a computational pipeline, called DTINet, to predict novel drug–target interactions from a constructed heterogeneous network, which integrates diverse drug-related information. DTINet focuses on learning a low-dimensional vector representation of features, which accurately explains the topological properties of individual nodes in the heterogeneous network, and then makes prediction based on these representations via a vector space projection scheme. DTINet achieves substantial performance improvement over other state-of-the-art methods for drug–target interaction prediction. Moreover, we experimentally validate the novel interactions between three drugs and the cyclooxygenase proteins predicted by DTINet, and demonstrate the new potential applications of these identified cyclooxygenase inhibitors in preventing inflammatory diseases. These results indicate that DTINet can provide a practically useful tool for integrating heterogeneous information to predict new drug–target interactions and repurpose existing drugs. Network-based data integration for drug–target prediction is a promising avenue for drug repositioning, but performance is wanting. Here, the authors introduce DTINet, whose performance is enhanced in the face of noisy, incomplete and high-dimensional biological data by learning low-dimensional vector representations.

The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern. It is imperative to identify these patients early. We show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission. We develop this model using a cohort of 1590 patients from 575 medical centers, with internal validation performance of concordance index 0.894 We further validate the model on three separate cohorts from Wuhan, Hubei and Guangdong provinces consisting of 1393 patients with concordance indexes of 0.890, 0.852 and 0.967 respectively. This model is used to create an online calculation tool designed for patient triage at admission to identify patients at risk of severe illness, ensuring that patients at greatest risk of severe illness receive appropriate care as early as possible and allow for effective allocation of health resources. The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern and early assessment would be vital. Here, the authors show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission.

Photoluminescent graphene quantum dots (GQDs) have received enormous attention because of their unique chemical, electronic and optical properties. Here a series of GQDs were synthesized under hydrothermal processes in order to investigate the formation process and optical properties of N-doped GQDs. Citric acid (CA) was used as a carbon precursor and self-assembled into sheet structure in a basic condition and formed N-free GQD graphite framework through intermolecular dehydrolysis reaction. N-doped GQDs were prepared using a series of N-containing bases such as urea. Detailed structural and property studies demonstrated the formation mechanism of N-doped GQDs for tunable optical emissions. Hydrothermal conditions promote formation of amide between –NH 2 and –COOH with the presence of amine in the reaction. The intramoleculur dehydrolysis between neighbour amide and COOH groups led to formation of pyrrolic N in the graphene framework. Further, the pyrrolic N transformed to graphite N under hydrothermal conditions. N-doping results in a great improvement of PL quantum yield (QY) of GQDs. By optimized reaction conditions, the highest PL QY (94%) of N-doped GQDs was obtained using CA as a carbon source and ethylene diamine as a N source. The obtained N-doped GQDs exhibit an excitation-independent blue emission with single exponential lifetime decay.

Regulation of stimulator of interferon genes (STING) pathway using agonists can boost antitumor immunity for cancer treatment, while the rapid plasma clearance, limited membrane permeability, and inefficient cytosolic transport of STING agonists greatly compromise their therapeutic efficacy. In this study, we describe an extracellular matrix (ECM)-degrading nanoagonist (dNAc) with second near-infrared (NIR-II) light controlled activation of intracellular STING pathway for mild photothermal-augmented chemodynamic-immunotherapy of breast cancer. The dNAc consists of a thermal-responsive liposome inside loading with ferrous sulfide (FeS 2 ) nanoparticles as both NIR-II photothermal converters and Fenton catalysts, 2′3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) as the STING agonist, and an ECM-degrading enzyme (bromelain) on the liposome surface. Mild heat generated by dNAc upon NIR-II photoirradiation improves Fenton reaction efficacy to kill tumor cells and cause immunogenic cell death (ICD). Meanwhile, the generated heat triggers a controlled release of cGAMP from thermal-responsive liposomes to active STING pathway. The mild photothermal activation of STING pathway combined with ICD promotes anti-tumor immune responses, which leads to improved infiltration of effector T cells into tumor tissues after bromelain-mediated ECM degradation. As a result, after treatment with dNAc upon NIR-II photoactivation, both primary and distant tumors in a murine mouse model are inhibited and the liver and lung metastasis are effectively suppressed. This work presents a photoactivatable system for STING pathway and combinational immunotherapy with improved therapeutic outcome. Graphical Abstract

Immunotherapy is an attractive treatment strategy for cancer, while its efficiency and safety need to be improved. A dual‐cascade activatable nanopotentiator for sonodynamic therapy (SDT) and chemodynamic therapy (CDT)‐cooperated immunotherapy of deep tumors via reshaping adenosine metabolism is herein reported. This nanopotentiator (NPMCA) is constructed through crosslinking adenosine deaminase (ADA) with chlorin e6 (Ce6)‐conjugated manganese dioxide (MnO2) nanoparticles via a reactive oxygen species (ROS)‐cleavable linker. In the tumor microenvironment with ultrasound (US) irradiation, NPMCA mediates CDT and SDT concurrently in deep tumors covered with 2‐cm tissues to produce abundant ROS, which results in dual‐cascade scissoring of ROS‐cleavable linkers to activate ADA within NCMCA to block adenosine metabolism. Moreover, immunogenic cell death (ICD) of dying tumor cells and upregulation of the stimulator of interferon genes (STING) is triggered by the generated ROS and Mn2+ from NPMCA, respectively, leading to activation of antitumor immune response. The potency of immune response is further reinforced by reducing the accumulation of adenosine in tumor microenvironment by the activated ADA. As a result, NPMCA enables CDT and SDT‐cooperated immunotherapy, showing an obviously improved therapeutic efficacy to inhibit the growths of bilateral tumors, in which the primary tumors are covered with 2‐cm tissues. An ultrasound and tumor microenvironment dual‐cascade activatable nanopotentiator is constructed for sono‐chemodynamic‐immunotherapy of deep tumors. The nanopotentiator produces abundant reactive oxygen species for inducing immunogenic cell death and activating adenosine deaminase to reshape the adenosine metabolism. Thus, the antitumor immune response is obviously amplified by sono‐chemodynamic‐cooperated immunotherapy to effectively treat deep 4T1 tumors covered with 2‐cm tissues.

The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn2+ store, and excessive mitochondrial Zn2+ is linked to neurodegeneration. How mitochondria maintain their Zn2+ homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn2+ from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to elevated Zn2+ levels in mitochondria, a severely swollen mitochondrial matrix in many tissues, compromised mitochondrial metabolic function, reductive stress, and induction of the mitochondrial stress response. SLC-30A9 is also essential for organismal fertility and sperm activation in C. elegans, during which Zn2+ exits from mitochondria and acts as an activation signal. In slc-30a9–deficient neurons, misshapen mitochondria show reduced distribution in axons and dendrites, providing a potential mechanism for the Birk–Landau–Perez cerebrorenal syndrome where an SLC30A9 mutation was found.

A bstract We perform three dimensional lattice simulation of the electroweak symmetry breaking process through two-step vacuum-like phase transitions with one step being first-order. Our results show that: 1) when the electroweak symmetry breaking is driven by the beyond Standard Model theories through the Higgs-portal , the gravitational wave spectra produced from the phase transitions are of broken power-law shape; 2) when the electroweak symmetry breaking is induced by a first-order phase transition of a high-scale theory respecting the global U(1) symmetry, cosmic strings can form and then decay through particle radiation. The two scenarios can be distinguished through probing the stochastic gravitational wave backgrounds. Our study suggests that the stochastic gravitational wave backgrounds provide an alternative way to probe the beyond Standard Model theories relevant to the electroweak symmetry breaking in the early Universe.

Background Diabetes complications are the leading cause of mortality in diabetic patients. The common complications are decline in antioxidant capacity and the onset of micro-inflammation syndrome. At present, glucose-responsive nanoparticles are widely used, as they can release insulin-loaded ultrafine particles intelligently and effectively reduce blood sugar. However, the toxicology of this method has not been fully elucidated. The plant extracts of pterostilbene (PTE) have a wide range of biological applications, such as antioxidation and inflammatory response improvement. Therefore, we have proposed new ideas for the cross application of plant extracts and biomaterials, especially as part of a hypoglycaemic nano-drug delivery system. Results Based on the PTE, we successfully synthesised poly(3-acrylamidophenyl boric acid-b-pterostilbene) (p[AAPBA-b-PTE]) nanoparticles (NPs). The NPs were round in shape and ranged between 150 and 250 nm in size. The NPs possessed good pH and glucose sensitivity. The entrapment efficiency (EE) of insulin-loaded NPs was approximately 56%, and the drug loading (LC) capacity was approximately 13%. The highest release of insulin was 70%, and the highest release of PTE was 85%. Meanwhile, the insulin could undergo self-regulation according to changes in the glucose concentration, thus achieving an effective, sustained release. Both in vivo and in vitro experiments showed that the NPs were safe and nontoxic. Under normal physiological conditions, NPs were completely degraded within 40 days. Fourteen days after mice were injected with p(AAPBA-b-PTE) NPs, there were no obvious abnormalities in the heart, liver, spleen, lung, or kidney. Moreover, NPs effectively reduced blood glucose, improved antioxidant capacity and reversed micro-inflammation in mice. Conclusions p(AAPBA-b-PTE) NPs were successfully prepared using PTE as raw material and effectively reduced blood glucose, improved antioxidant capacity and reduced the inflammatory response. This novel preparation can enable new combinations of plant extracts and biomaterials to adiministered through NPs or other dosage forms in order to regulate and treat diseases. Graphic abstract