In vivo clinical molecular imaging of T cell activity.

Tumor immunotherapy is refashioning traditional treatments in the clinic for certain tumors, especially by relying on the activation of T cells. However, the safety and effectiveness of many antitumor immunotherapeutic agents are suboptimal due to difficulties encountered in assessing T cell responses and adjusting treatment regimens accordingly. Here, we review advances in the clinical visualization of T cell activity in vivo, and focus particularly on molecular imaging probes and biomarkers of T cell activation. Current challenges and prospects are also discussed that aim to achieve a better strategy for real-time monitoring of T cell activity, predicting prognoses and responses to tumor immunotherapy, and assessing disease management.

Twisted van der Waals Quantum Materials: Fundamentals, Tunability, and Applications.

Twisted van der Waals (vdW) quantum materials have emerged as a rapidly developing field of two-dimensional (2D) semiconductors. These materials establish a new central research area and provide a promising platform for studying quantum phenomena and investigating the engineering of novel optoelectronic properties such as single photon emission, nonlinear optical response, magnon physics, and topological superconductivity. These captivating electronic and optical properties result from, and can be tailored by, the interlayer coupling using moiré patterns formed by vertically stacking atomic layers with controlled angle misorientation or lattice mismatch. Their outstanding properties and the high degree of tunability position them as compelling building blocks for both compact quantum-enabled devices and classical optoelectronics. This paper offers a comprehensive review of recent advancements in the understanding and manipulation of twisted van der Waals structures and presents a survey of the state-of-the-art research on moiré superlattices, encompassing interdisciplinary interests. It delves into fundamental theories, synthesis and fabrication, and visualization techniques, and the wide range of novel physical phenomena exhibited by these structures, with a focus on their potential for practical device integration in applications ranging from quantum information to biosensors, and including classical optoelectronics such as modulators, light emitting diodes, lasers, and photodetectors. It highlights the unique ability of moiré superlattices to connect multiple disciplines, covering chemistry, electronics, optics, photonics, magnetism, topological and quantum physics. This comprehensive review provides a valuable resource for researchers interested in moiré superlattices, shedding light on their fundamental characteristics and their potential for transformative applications in various fields.

Selective PPARγ modulator diosmin improves insulin sensitivity and promotes browning of white fat.

Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation, glucolipid metabolism, and inflammation. Thiazolidinediones are PPARγ full agonists with potent insulin-sensitizing effects, whereas their oral usage is restricted because of unwanted side effects, including obesity and cardiovascular risks. Here, via virtual screening, microscale thermophoresis analysis, and molecular confirmation, we demonstrate that diosmin, a natural compound of wide and long-term clinical use, is a selective PPARγ modulator that binds to PPARγ and blocks PPARγ phosphorylation with weak transcriptional activity. Local diosmin administration in subcutaneous fat (inguinal white adipose tissue [iWAT]) improved insulin sensitivity and attenuated obesity via enhancing browning of white fat and energy expenditure. Besides, diosmin ameliorated inflammation in WAT and liver and reduced hepatic steatosis. Of note, we determined that iWAT local administration of diosmin did not exhibit obvious side effects. Taken together, the present study demonstrated that iWAT local delivery of diosmin protected mice from diet-induced insulin resistance, obesity, and fatty liver by blocking PPARγ phosphorylation, without apparent side effects, making it a potential therapeutic agent for the treatment of metabolic diseases.

DFT Study of Metal (Ag, Au, Pt)-Modified SnS2 for Adsorption of SF6 Decomposition Gases in Gas-Insulated Switchgear.

In this study, the gas-sensitive response of metal (Ag, Au, Pt)-modified SnS2 toward SF6 decomposition gases (SOF2, SO2F2, SO2, H2S) in gas-insulated switchgear was studied by analyzing the adsorption structure, band structure, charge transfer, and density of states based on density functional theory. The results show that the adsorption of the four target gases on pristine SnS2 belongs to weak physical adsorption. Compared with the pristine SnS2, the adsorption energy of the transition metal atom-modified SnS2 monolayer has been improved to a certain extent and the adsorption capacity of these four gases on the transition metal atom-modified SnS2 monolayer has obviously improved. Moreover, the recovery time of Ag-SnS2/SOF2, Ag-SnS2/SO2F2, Au-SnS2/SOF2, Au-SnS2/SO2F2, and Pt-SnS2/SO2F2 is too short, indicating that these conditions have poor adsorption capacity and sensitivity to SF6 decomposition gases and are not suitable as detection materials for these gases. According to the different changes in conductivity during adsorption, it provides a feasible solution to detect each SF6 decomposition gas. This theoretical study effectively explained the adsorption and sensing properties between the metal-modified monolayers and gases.

Surface ligand-regulated renal clearance of MRI/SPECT dual-modality nanoprobes for tumor imaging.

BACKGROUND: The general sluggish clearance kinetics of functional inorganic nanoparticles tend to raise potential biosafety concerns for in vivo applications. Renal clearance is a possible elimination pathway for functional inorganic nanoparticles delivered through intravenous injection, but largely depending on the surface physical chemical properties of a given particle apart from its size and shape. RESULTS: In this study, three small-molecule ligands that bear a diphosphonate (DP) group, but different terminal groups on the other side, i.e., anionic, cationic, and zwitterionic groups, were synthesized and used to modify ultrasmall Fe3O4 nanoparticles for evaluating the surface structure-dependent renal clearance behaviors. Systematic studies suggested that the variation of the surface ligands did not significantly increase the hydrodynamic diameter of ultrasmall Fe3O4 nanoparticles, nor influence their magnetic resonance imaging (MRI) contrast enhancement effects. Among the three particle samples, Fe3O4 nanoparticle coated with zwitterionic ligands, i.e., Fe3O4@DMSA, exhibited optimal renal clearance efficiency and reduced reticuloendothelial uptake. Therefore, this sample was further labeled with 99mTc through the DP moieties to achieve a renal-clearable MRI/single-photon emission computed tomography (SPECT) dual-modality imaging nanoprobe. The resulting nanoprobe showed satisfactory imaging capacities in a 4T1 xenograft tumor mouse model. Furthermore, the biocompatibility of Fe3O4@DMSA was evaluated both in vitro and in vivo through safety assessment experiments. CONCLUSIONS: We believe that the current investigations offer a simple and effective strategy for constructing renal-clearable nanoparticles for precise disease diagnosis.

On formation, annihilation, and evolution of potential wells, and nonlinear phenomena of multi-magnet energy sink system.

This paper investigates the formation, annihilation, and evolution mechanisms of potential energy wells in nonlinear energy sink systems. The nonlinear energy sink system is composed of multiple inner and outer magnets. Two multi-magnet energy sink (MES) architectures are designed: a single-magnet vibrator and a double-magnet vibrator. Multi-stable (bi-, tri-, quad-, penta-, hexa-, and hepta-stable) mechanisms are elaborated by the Poincaré section and bifurcation diagram concerning the magnet length, the link length, and the MES configuration. The results show that the change in the internal structural parameters of the MES system will generate different types of bifurcations (i.e., saddle-node, subcritical, and super pitchfork bifurcations) and phase trajectories and have rich nonlinear response behaviors in the low frequency and wide frequency range, which can be used for damping and vibration reduction of engineering structures, vibration control, and energy source of the microgrid.

An Improved OMP Algorithm for Enhancing the Anti-Interference Performance of Array Antennas.

The demand for precise positioning in noisy environments has propelled the development of research on array antenna radar systems. Although the orthogonal matching pursuit (OMP) algorithm demonstrates superior performance in signal reconstruction, its application efficacy in noisy settings faces challenges. Consequently, this paper introduces an innovative OMP algorithm, DTM_OMP_ICA (a dual-threshold mask OMP algorithm based on independent component analysis), which optimizes the OMP signal reconstruction framework by utilizing two different observation bases in conjunction with independent component analysis (ICA). By implementing a mean mask strategy, it effectively denoises signals received by array antennas in noisy environments. Simulation results reveal that compared to traditional OMP algorithms, the DTM_OMP_ICA algorithm shows significant advantages in noise suppression capability and algorithm stability. Under optimal conditions, this algorithm achieves a noise suppression rate of up to 96.8%, with its stability also reaching as high as 99%. Furthermore, DTM_OMP_ICA surpasses traditional denoising algorithms in practical denoising applications, proving its effectiveness in reconstructing array antenna signals in noisy settings. This presents an efficient method for accurately reconstructing array antenna signals against a noisy backdrop.

Intranasal Pathway for Nanoparticles to Enter the Central Nervous System.

Intranasal administration was previously proposed for delivering drugs for central nervous system (CNS) diseases. However, the delivery and elimination pathways, which are very imperative to know for exploring the therapeutic applications of any given CNS drugs, remain far from clear. Because lipophilicity has a high priority in the design of CNS drugs, the as-prepared CNS drugs tend to form aggregates. Therefore, a PEGylated Fe3O4 nanoparticle labeled with a fluorescent dye was prepared as a model drug and studied to elucidate the delivery pathways of intranasally administered nanodrugs. Through magnetic resonance imaging, the distribution of the nanoparticles was investigated in vivo. Through ex vivo fluorescence imaging and microscopy studies, more precise distribution of the nanoparticles across the entire brain was disclosed. Moreover, the elimination of the nanoparticles from cerebrospinal fluid was carefully studied. The temporal dose levels of intranasally delivered nanodrugs in different parts of the brain were also investigated.

A review on spent Mn-containing Li-ion batteries: Recovery technologies, challenges, and future perspectives.

Mn-containing Li-ion batteries have become primary power sources for electronic devices and electric vehicles because of their high-energy density, extended cycle life, low cost, and heightened safety. In recent years, Li-ion batteries (LIBs) have undergone rapid updates, paralleling the swift advancement of the lithium battery industry, resulting in a growing accumulation of LIB scraps annually, necessitating comprehensive recovery strategies. This article reviews the recent progress in recovering spent Mn-containing LIBs (SM-LIBs), specifically focusing on LiMn2O4 and ternary LiCoxMnyNizO2 (NCM). Initially, the study analyzes the current resource profile of SM-LIBs and elucidates their service mechanisms. Subsequently, the study explores the recovery of SM-LIBs, discussing various methods such as the hydrometallurgical approach, combined pyrolytic treatment-wet leaching process, bioleaching pathway, and electrochemical extraction. These discussions include recovery processes, reaction principles, and technological features. In addition, this study evaluates the potential applications of these recovery technologies, considering aspects such as complexity, economic viability, energy consumption, environmental sustainability, and scalability. Finally, it summarizes the challenges associated with the comprehensive recovery and resource utilization of SM-LIBs and offers insights into future directions.

Observing multiple processes of backward-phase-matching spontaneous parametric downconversion in a single-periodic crystal.

A nonlinear process based on backward quasi-phase matching (BQPM) can be used to realize mirrorless optical parametric oscillation, the generation of paired photons with a separable joint spectral amplitude and narrow wavelength bandwidth, and the preparation of counterpropagating polarization-entangled photons, which shows distinct advantages over some applications based on forward quasi-phase matching. In this work, three types of BQPM in a bulk periodically poled potassium titanyl phosphate crystal with a single period are theoretically analyzed. Experimentally, the harmonic wave generated by second-harmonic generation in type 0 and type I exhibits a narrow bandwidth of 15.5 GHz. Furthermore, photon pairs generated by spontaneous parametric downconversion in all types of BQPM (type 0, type I, and type II) at 7th order are observed and characterized. Their coincidence-to-accidental ratios are all greater than 5 × 103 in the pump power range from 10 mW to 500 mW. This research lays the foundation for further applications of BQPM in nonlinear optics, quantum optics, and quantum information processing.

Design, synthesis and SAR of novel 7-azaindole derivatives as potential Erk5 kinase inhibitor with anticancer activity.

The extracellular signal-regulated kinase 5 (Erk5) signaling plays a crucial role in cancer, and regulating its activity may have potential in cancer chemotherapy. In this study, a series of novel 7-azaindole derivatives (4a-5o) were designed and synthesized. Their antitumor activities on human lung cancer A549 cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole (DAPI) staining and colony formation assay. Among them, compounds 4a, 4 h, 5d and 5j exhibited good anti-proliferative activity with the IC50 values of 6.23 µg/mL, 8.52 µg/mL, 7.33 µg/mL and 4.56 µg/mL, respectively, equivalent to Erk5 positive control XMD8-92 (IC50 = 5.36 µg/mL). The results of structure-activity relationships (SAR) showed that double bond on the piperidine ring and N atoms at the N7 position of 7-azaindole was essential for their antiproliferative activity. Furthermore, compounds 4a and 5j exhibited good inhibition on Erk5 kinase through Western blot analysis and possible action site of compounds with Erk5 kinase was elucidated by molecular docking.

An Ultrasonic RF Acquisition System for Plant Stems Based on Labview Double Layer Multiple Triggering.

Ultrasound is widely used in medical and engineering inspections due to its non-destructive and easy-to-use characteristics. However, the complex internal structure of plant stems presents challenges for ultrasound testing. The density and thickness differences in various types of stems can cause different attenuation of ultrasonic signal propagation and the formation of different echo locations. To detect structural changes in plant stems, it is crucial to acquire complete ultrasonic echo RF signals. However, there is currently no dedicated ultrasonic RF detection equipment for plant stems, and some ultrasonic acquisition equipment has limited memory capacity that cannot store a complete echo signal. To address this problem, this paper proposes a double-layer multiple-timing trigger method, which can store multiple trigger sampling memories to meet the sampling needs of different plant stems with different ultrasonic echo locations. The method was tested in experiments and found to be effective in acquiring complete ultrasonic RF echo signals for plant stems. This approach has practical significance for the ultrasonic detection of plant stems.

[Segmentation of prostate region in magnetic resonance images based on improved V-Net].

Magnetic resonance (MR) imaging is an important tool for prostate cancer diagnosis, and accurate segmentation of MR prostate regions by computer-aided diagnostic techniques is important for the diagnosis of prostate cancer. In this paper, we propose an improved end-to-end three-dimensional image segmentation network using a deep learning approach to the traditional V-Net network (V-Net) network in order to provide more accurate image segmentation results. Firstly, we fused the soft attention mechanism into the traditional V-Net's jump connection, and combined short jump connection and small convolutional kernel to further improve the network segmentation accuracy. Then the prostate region was segmented using the Prostate MR Image Segmentation 2012 (PROMISE 12) challenge dataset, and the model was evaluated using the dice similarity coefficient (DSC) and Hausdorff distance (HD). The DSC and HD values of the segmented model could reach 0.903 and 3.912 mm, respectively. The experimental results show that the algorithm in this paper can provide more accurate three-dimensional segmentation results, which can accurately and efficiently segment prostate MR images and provide a reliable basis for clinical diagnosis and treatment.

Near-Infrared Afterglow Luminescence of Chlorin Nanoparticles for Ultrasensitive In Vivo Imaging.

Afterglow imaging holds great potential for ultrasensitive biomedical imaging. As it detects photons after the cessation of real-time light excitation, autofluorescence can therefore be effectively eliminated. However, afterglow imaging is still in its infant stage due to the lack of afterglow agents with satisfactory lifetime, biocompatibility, and high luminescence brightness, particularly afterglow in the near-infrared region for in vivo applications. To address these issues, this study for the first time reports chlorin nanoparticles (Ch-NPs) emitting afterglow luminescence peaking at 680 nm with a half-life of up to 1.5 h, which is almost 1 order of magnitude longer than those of other reported organic afterglow probes. In-depth experimental and theoretical studies revealed that the brightness of the afterglow luminescence is strongly correlated with the singlet oxygen (1O2) capacity and the oxidizability of the chlorins. Benefitting from the ultralong half-life and the minimized imaging background, small metastatic tumor foci of 3 mm3 were successfully resected under the guidance of the afterglow luminescence generated upon a single shot of activation prior to the injection, which was impossible for conventional near-infrared fluorescence imaging due to tissue autofluorescence.

Healing Diabetic Ulcers with MoO3-X Nanodots Possessing Intrinsic ROS-Scavenging and Bacteria-Killing Capacities.

Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine treatment combining surgical debridement with anti-infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long-term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum-based nanodots (MoO3-X ) for healing the DUs are reported. The ROS scavenging ability of MoO3-X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO3-X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin-resistant Staphylococcus aureus, manifesting the potent application prospect of MoO3-X nanodots for diabetic wound therapy.

Detection of Water Changes in Plant Stems In Situ by the Primary Echo of Ultrasound RF with an Improved AIC Algorithm.

The detection of water changes in plant stems by non-destructive online methods has become a hot spot in studying the physiological activity of plant water. In this paper, the ultrasonic radio-frequency echo (RFID) technique was used to detect water changes in stems. An algorithm (improved hybrid differential Akaike's Information Criterion (AIC)) was proposed to automatically compute the position of the primary ultrasonic echo of stems, which is the key parameter of water changes in stems. This method overcame the inaccurate location of the primary echo, which was caused by the anisotropic ultrasound propagation and heterogeneous stems. First of all, the improved algorithm was analyzed and its accuracy was verified by a set of simulated signals. Then, a set of cutting samples from stems were taken for ultrasonic detection in the process of water absorption. The correlation between the moisture content of stems and ultrasonic velocities was computed with the algorithm. It was found that the average correlation coefficient of the two parameters reached about 0.98. Finally, living sunflowers with different soil moistures were subjected to ultrasonic detection from 9:00 to 18:00 in situ. The results showed that the soil moisture and the primary ultrasonic echo position had a positive correlation, especially from 12:00 to 18:00; the average coefficient was 0.92. Meanwhile, our results showed that the ultrasonic detection of sunflower stems with different soil moistures was significantly distinct. Therefore, the improved AIC algorithm provided a method to effectively compute the primary echo position of limbs to help detect water changes in stems in situ.

Functionalized Ultrasmall Iron Oxide Nanoparticles for T1-Weighted Magnetic Resonance Imaging of Tumor Hypoxia.

Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment's therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitive T1-weighted MRI probe (Fe3O4-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe3O4) nanoparticles. The results of in vitro and in vivo experiments show that Fe3O4-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia via T1-weighted MRI. These promising results may unlock the potential of Fe3O4 nanoparticles as T1-weighted contrast agents for the development of clinical hypoxia probes.

Furin Enzyme and pH Synergistically Triggered Aggregation of Gold Nanoparticles for Activated Photoacoustic Imaging and Photothermal Therapy of Tumors.

Specific and effective accumulation of nanoparticles within tumors is highly crucial for precise cancer diagnosis and treatment. Therefore, spatiotemporally manipulating the aggregation of small gold nanoparticles (AuNPs) in a tumor microenvironment is of great significance for enhancing the diagnostic and therapeutic efficacy of tumors. Herein, we reported a novel furin enzyme/acidic pH synergistically triggered small AuNP aggregation strategy for activating the photoacoustic (PA) imaging and photothermal (PTT) functions of AuNPs in vivo. Smart gold nanoparticles decorated with furin-cleavable RVRR (Arg-Val-Arg-Arg) peptides (Au-RRVR) were rationally designed and fabricated. Both in vitro and in vivo experiments demonstrated that such Au-RRVR nanoparticles could be simultaneously induced by furin and acidic pH to form large aggregates within tumorous tissue resulting in improved tumor accumulation and retention, which can further activate the PA and PTT effect of AuNPs for sensitive imaging and efficient therapy of tumors. Thus, we believe that this dual-stimuli-responsive aggregation system may offer a universal platform for effective cancer diagnosis and treatment.

Anchoring Group Mediated Radiolabeling for Achieving Robust Nanoimaging Probes.

Radiolabeling counts for much in the functionalization of inorganic nanoparticles (NPs) because it endows NPs with high-sensitive imaging capacities apart from providing accurate pharmacokinetic information on the labeled particles, which makes the development of relevant radiolabeling chemistry highly desirable. Herein, a novel Ligand Anchoring Group MEdiated RAdioLabeling (LAGMERAL) method is reported, in which a polyethylene glycol (PEG) ligand with a diphosphonate (DP) terminal group plays a key role. It offers possibilities to radiolabel NPs through the spare coordination sites of the DP anchoring group. Through X-ray absorption spectroscopy studies, the coordination states of the foreign metal ions on the particle surface are investigated. In addition, radioactive Fe3 O4 NPs are prepared by colabeling the particles with 125 I at the outskirt of the particles through a phenolic hydroxyl moiety of the PEG ligand, and 99m Tc at the root of the ligand, respectively. In this way, the stabilities of these types of radiolabeling are compared both in vitro and in vivo to show the advantages of the LAGMERAL method. The outstanding stability of probe and simplicity of the labeling process make the current approach universal for creating advanced NPs with different combinations of functionalities of the inorganic NPs and radioactive properties of the metal radioisotopes.

Rapidly liver-clearable rare-earth core-shell nanoprobe for dual-modal breast cancer imaging in the second near-infrared window.

BACKGROUND: Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200-400 nm) and visible light (Vis, 400-650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000-1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. RESULTS: Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core-shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What's more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. CONCLUSIONS: The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision.