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This work successfully introduced the different ratios of metallic Cr into micrometer Si bulk via a high-energy ball-milling method to synthesize nanostructured Si/CrSi2alloy anodes with enhanced electrochemical performance in lithium-ion batteries (LIBs). This study demonstrated that the in situ-formed CrSi2could effectively suppress the generation of crystalline Li3.75Si in the lithiation process, dilute Si’s volume expansion, and improve electronic conductivity. Concretely, Si85Cr15displayed an outstanding reversible volumetric capacity of ∼1400 A h·L–1and 100-cycle capacity retention at 0.2 C of 90.1% with an average Coulombic efficiency of 99.46%. Moreover, another advantage of Si85Cr15is good compatibility with the carbon-coating treatment at 800 °C by virtue of the reinforced thermal stability derived from a high melting point of CrSi2. The homogeneous distribution of Si and metal silicide crystallites was better maintained in Si85Cr15@c-PDA compared to our previously annealed Si–Cu3Si–NiSi2alloys at the same temperature. Correspondingly, the cycle stability and rate capability of Si85Cr15@c-PDA were further improved with a capacity retention of 93.1/90.6% at 0.2/0.5 C (100/200 cycles) and 40% at 2 C, respectively. The excellent electrochemical performance indicates that Si/CrSi2alloys may be prospective candidates as compositions in the carbon-coated anode materials for industrialized LIBs.

Metal oxides based aqueous supercapacitors are promising sustainable energy storage devices due to their high specific capacitance, but the bottleneck is how to efficiently utilize the active materials. Adoption of 3D porous current collectors is an efficient method to elevate the mass load of active materials in the electrodes without sacrificing their specific capacitance. 3D porous ZnO@Ni electrodes are fabricated in this work, and KOH/Zn(Ac)2is adopted as the electrolyte. The interactions between the electrodes and the electrolytes lead to the in situ generation and recrystallization of active materials. The ZnO@Ni electrodes can function as both negative and positive electrodes, and show a capacitance of 1074.1 and 1871.7 F/cm3, respectively. Symmetric ZnO@Ni supercapacitors are fabricated, and exhibit a high energy density of 185.8 mWh/cm3. The ZnO@Ni supercapacitors sealed in commercial coincells also show a stable performance, and are demonstrated to power electric motors.

As a promising new medical imaging method, photoacoustic imaging (PAI) has the advantages of optical resolution and acoustic depth of penetration. The transparent ultrasound transducer (TUT), as a novel device applied to PAI, can combine the laser and acoustic beam coaxially to improve the imaging quality. Transparent piezoelectric materials are the key to developing piezoelectric TUTs. However, due to the birefringence and light scattering caused by ferroelectric domains, it is very hard to prepare transparent piezoelectric materials with both high optical transmittance and excellent piezoelectricity. In this study, 2.5 mol% Sm-doped 0.72Pb(Mg1/3Nb2/3)O3-0.28PbTiO3(PMN-PT) ceramic with a piezoelectric coefficient d33of 1460 pC N−1and an optical transmission of 69 % at Near-Infrared (NIR) is successfully prepared, and its optical, microstructure, ferroelectric and dielectric properties are fully studied. Subsequently, a 3 mm-diameter photoacoustic coaxial probe is fabricated, involving a transparent ultrasound transducer based on the prepared ceramic. The TUT has a center frequency (fc) of 18.5 MHz, a −6 dB bandwidth of 20 %, and a high effective electromechanical factor (keff)of 0.62. In addition, the imaging capability of the miniature probe is firstly confirmed through photoacoustic/ultrasound dual-modality imaging of in-vivoanimals and phantoms, which indicates that the proposed transparent piezoelectric ceramic has great potential for PA/US imaging.

While covalent drug discovery is reemerging as an important route to small-molecule therapeutic leads, strategies for the discovery and engineering of protein-based irreversible binding agents remain limited. Here, we describe the use of yeast display in combination with noncanonical amino acids (ncAAs) to identify irreversible variants of single-domain antibodies (sdAbs), also called VHHs and nanobodies, targeting botulinum neurotoxin light chain A (LC/A). Starting from a series of previously described, structurally characterized sdAbs, we evaluated the properties of antibodies substituted with reactive ncAAs capable of forming covalent bonds with nearby groups after UV irradiation (when using 4-azido-l-phenylalanine) or spontaneously (when using O-(2-bromoethyl)-l-tyrosine). Systematic evaluations in yeast display format of more than 40 ncAA-substituted variants revealed numerous clones that retain binding function while gaining either UV-mediated or spontaneous crosslinking capabilities. Solution-based analyses indicate that ncAA-substituted clones exhibit site-dependent target specificity and crosslinking capabilities uniquely conferred by ncAAs. Interestingly, not all ncAA substitution sites resulted in crosslinking events, and our data showed no apparent correlation between detected crosslinking levels and distances between sdAbs and LC/A residues. Our findings highlight the power of yeast display in combination with genetic code expansion in the discovery of binding agents that covalently engage their targets. This platform streamlines the discovery and characterization of antibodies with therapeutically relevant properties that cannot be accessed in the conventional genetic code.

State of Charge (SoC) is an essential indicator for energy storage distribution in lithium-ion batteries, which prevents overcharge and over-discharge of the battery by integrating it into the Battery Management System. Common estimation approaches are Extended Kalman Filtering (EKF), Coulomb counting, open-circuit-voltage (OCV), and neural networks (NN). While these methods are able to estimate SoC more accurately, they lack real-time monitoring capability for internal and external battery damage such as air bubbles and foreign objects. This study is the first to propose a novel joint algorithm for real-time monitoring of battery SoC and health with high accuracy, integrating ultrasonic non-destructive testing (NDT). The proposed algorithm predicts the battery overcharge based on the ultrasonic signal and reveals structural changes in commercial batteries during charging/discharging. Experimental results demonstrate that ultrasonic inspection cannot only enhance the SoC estimation accuracy of the backpropagation (BP) neural network, but also detects damaged conditions of the battery.

The development of nanotheranostics for precision imaging-guided regulated cell death-mediated synergistic tumor therapy is still challenging. Herein, a novel multifunctional nanotheranostic agent, iRGD-coated maleimide-poly(ethylene glycol)-poly(lactic acid/glycolic acid)-encapsulated hydrophobic gold nanocages (AuNCs) and hydrophilic epigallocatechin gallate (EGCG) (PAuE) is developed for multispectral optoacoustic tomography (MSOT)-guided photothermal therapy (PTT) and chemotherapy. The portions of necroptotic and apoptotic tumor cells were 52.9 and 5.4%, respectively, at 6 h post-incubation after the AuNC-induced mild PTT treatment, whereas they became 14.0 and 46.1% after 24 h, suggesting that the switch of the cell death pathway is a time-dependent process. Mild PTT facilitated the release of EGCG which induces the downregulation of hypoxia-inducible factor-1 (HIF-1α) expression to enhance apoptosis at a later stage, realizing a remarkable tumor growth inhibition in vivo. Moreover, RNA sequence analyses provided insights into the significant changes in genes related to the cross-talk between necroptosis and apoptosis pathways via PAuE upon laser irradiation. In addition, the biodistribution and metabolic pathways of PAuE have been successfully revealed by 3D MSOT. Taken together, this strategy of first combination of EGCG and AuNC-based photothermal agent via triggering necroptosis/apoptosis to downregulate HIF-1α expression in a tumor environment provides a new insight into anti-cancer therapy.

Two-dimensional (2D)-layered atomic arrangement with ultralow lattice thermal conductivity and ultrahigh figure of merit in single-crystalline SnSe drew significant attention among all thermoelectric materials. However, the processing of polycrystalline SnSe with equivalent thermoelectric performance as single-crystal SnSe will have great technological significance. Herein, we demonstrate a high zTof 2.4 at 800 K through the optimization of intrinsic defects in polycrystalline SnSe via controlled alpha irradiation. Through a detailed theoretical calculation of defect formation energies and lattice dynamic phonon dispersion studies, we demonstrate that the presence of intrinsically charged Sn vacancies can enhance the power factor and distort the lattice thermal conductivity by phonon-defect scattering. Supporting our theoretical calculations, the experimental enhancement in the electrical conductivity leads to a massive power factor of 0.9 mW/mK2and an ultralow lattice thermal conductivity of 0.22 W/mK through the vacancy-phonon scattering effect on polycrystalline SnSe. The strategy of intrinsic defect engineering of polycrystalline thermoelectric materials can increase the practical implementation of low-cost and high-performance thermoelectric generators.

Bivalent proteolysis-targeting chimeras (PROTACs) drive protein degradation by simultaneously binding a target protein and an E3 ligase and forming a productive ternary complex. We hypothesized that increasing binding valency within a PROTAC could enhance degradation. Here, we designed trivalent PROTACs consisting of a bivalent bromo and extra terminal (BET) inhibitor and an E3 ligand tethered via a branched linker. We identified von Hippel–Lindau (VHL)-based SIM1 as a low picomolar BET degrader with preference for bromodomain containing 2 (BRD2). Compared to bivalent PROTACs, SIM1 showed more sustained and higher degradation efficacy, which led to more potent anticancer activity. Mechanistically, SIM1 simultaneously engages with high avidity both BET bromodomains in a cisintramolecular fashion and forms a 1:1:1 ternary complex with VHL, exhibiting positive cooperativity and high cellular stability with prolonged residence time. Collectively, our data along with favorable in vivo pharmacokinetics demonstrate that augmenting the binding valency of proximity-induced modalities can be an enabling strategy for advancing functional outcomes.

Small-molecule-induced protein depletion technologies, also called inducible degrons, allow degradation of genetically engineered target proteins within cells and animals. Here, we design and develop the BromoTag, a new inducible degron system comprising a Brd4 bromodomain L387A variant as a degron tag that allows direct recruitment by heterobifunctional bumped proteolysis targeting chimeras (PROTACs) to hijack the VHL E3 ligase. We describe extensive optimization and structure–activity relationships of our bump-and-hole–PROTACs using a CRISPR knock-in cell line expressing model target BromoTag-Brd2 at endogenous levels. Collectively, our cellular and mechanistic data qualifies bumped PROTAC AGB1 as a potent, fast, and selective degrader of BromoTagged proteins, with a favorable pharmacokinetic profile in mice. The BromoTag adds to the arsenal of chemical genetic degradation tools allowing us to manipulate protein levels to interrogate the biological function and therapeutic potential in cells and in vivo.

Corneal neovascularization (CNV) compromises corneal avascularity and visual acuity. Current clinical visualization approaches are subjective and unable to provide molecular information. Photoacoustic (PA) imaging offers an objective and non-invasive way for angiogenesis investigation through hemodynamic and oxygen saturation level (sO_2) quantification. Here, we demonstrate the utility of PA and slit lamp microscope for in vivo rat CNV model. PA images revealed untreated corneas exhibited higher sO_2 level than treatment groups. The PA results complement with the color image obtained with slit lamp. These data suggest PA could offer an objective and non-invasive method for monitoring CNV progression and treatment outcome through the sO_2 quantification.

Myocardial infarctions are most often caused by the so-called vulnerable plaques, usually featured as non-obstructive lesions with a lipid-rich necrotic core, thin-cap fibroatheroma, and large plaque size. The identification and quantification of these characteristics are the keys to evaluate plaque vulnerability. However, single modality intravascular methods, such as intravascular ultrasound, optical coherence tomography and photoacoustic, can hardly achieve all the comprehensive information to satisfy clinical needs. In this paper, for the first time, we developed a novel multi-spectral intravascular tri-modality (MS-IVTM) imaging system, which can perform 360° continuous rotation and pull-backing with a 0.9-mm miniature catheter and achieve simultaneous acquisition of both morphological characteristics and pathological compositions. Intravascular tri-modality imaging demonstrates the ability of our MS-IVTM system to provide macroscopic and microscopic structural information of the vessel wall, with identity and quantification of lipids with multi-wavelength excitation. This study offers clinicians and researchers a novel imaging tool to facilitate the accurate diagnosis of vulnerable atherosclerotic plaques. It also has the potential of clinical translations to help better identify and evaluate high-risk plaques during coronary interventions.

Hydrogels are soft materials consisting of a three-dimensional network of polymer chains. Over the years, hydrogels with different compositions have been developed as drug carriers for diverse biomedical applications, ranging from cancer therapy and wound care to the treatment of neurodegenerative and inflammatory diseases. Most of these carriers, however, are designed only to deliver single agents. Carriers based on hydrogels for co-delivery of multiple agents, with the release rate of each of the co-delivered agents tunable, are lacking. This study reports a one-pot method of fabricating alginate-based complex fibers with the Janus morphology, with carboxymethyl cellulose sodium functioning as a polymeric modifier of the properties of each of the fiber compartments. By using malachite green and minocycline hydrochloride as model drugs, the generated fibers demonstrate the capacity of enabling the release profile of each of the co-delivered drugs to be precisely controlled. Along with their negligible toxicity and the retention of the activity of the loaded drugs, the complex fibers reported in this study warrant further development and optimization for applications that involve co-delivery of multiple agents.

Intravascular photoacoustic (IVPA) imaging technology enables the visualization of pathological characteristics (such as inflammation activities, lipid deposition) of the artery wall. Blood flushing is a necessary step in improving the imaging quality in in vivo IVPA imaging. But the limited imaging speed of the systems stretches their flushing time, which is an important obstacle of their clinical translations. In this paper, we report an improvement in IVPA/IVUS imaging speed to 100 frames per second. The high-speed imaging is demonstrated in rabbit in vivo, visualizing the nanoparticles accumulated on abdominal aorta wall at the wavelength of 1064 nm, in real time display. Blood flushing in vivo improves the IVPA signal-noise-ratio by around 3.5 dB. This study offers a stable, efficient and easy-to-use tool for instantaneous disease visualization and disease diagnosis in research and forwards IVPA/IVUS imaging technology towards clinical translations.

Lithium–sulfur (Li–S) batteries have been attracting great attention as promising rechargeable batteries because of their large specific capacity and high energy density. However, some technical problems still limit the commercialization value of Li–S batteries such as poor electrical conductivity, shuttle effects, and volume expansion. To overcome the aforementioned issues, N-doped carbon composites were synthesized via a one-step hydrothermal method. To obtain different N-doping configurations, a carbon precursor was annealed at different heating rates, resulting in different N-containing properties. The cell with the most content of pyridinic-N delivered the highest initial discharge capacity of ∼1121 mAh g–1, and the specific capacity still retained 605 mAh g–1at 200 mA g–1after 100 cycles. It was concluded that pyridinic-N has the most significant effect on immobilizing the soluble lithium polysulfides, which stabilized the cycle of Li–S batteries.

Symmetric sodium-ion batteries possess promising features such as low cost, easy manufacturing process, and facile recycling post-process, which are suitable for the application of large-scale stationary energy storage. Herein, we proposed a symmetric sodium-ion battery based on dual-electron reactions of a NASICON-structured Na3MnTi(PO4)3material. The Na3MnTi(PO4)3electrode can deliver a stable capacity of up to 160 mAh g–1with a Coulombic efficiency of 97% at 0.1 C by utilizing the redox reactions of Ti3+/4+, Mn2+/3+, and Mn3+/4+. This is the first time to investigate the symmetric sodium-ion full cell using Na3MnTi(PO4)3as both cathode and anode in the organic electrolyte, demonstrating excellent reversibility and cycling performance with voltage plateaus of about 1.4 and 1.9 V. The full cell exhibits a reversible capacity of 75 mAh g–1at 0.1 C and an energy density of 52 Wh kg–1. In addition, both ex situX-ray diffraction (XRD) analysis and first-principles calculations are employed to investigate the sodiation mechanism and structural evolution. The current research provides a feasible strategy for the symmetric sodium-ion batteries to achieve high energy density.

As the featured material of the superionic thermoelectric (TE) material family, copper-chalcogenide Cu2-xSe is attracting growing research interest for its excellent TE performance derived from the satisfactory power factor and the ultra-low thermal conductivity induced by the superionic effect. Various efforts have been made and proved to be effective to further enhance the TE performance for Cu2-xSe. However, this material is still far from the application stage, which is mainly due to concerns regarding control of the properties and the costly complex fabrication technology. Here we report a scalable pathway to achieve high-performance and tunable Cu2-xSe, utilizing conventional sintering technology and copper (Cu)-vacancy engineering with an effective mass model. The figure of merit zTis a competitive value of 1.0 at 800 K for the optimized binary Cu2-xSe, based on the precise modeling prediction and Cu-vacancy engineering. The changes in TE properties of Cu2-xSe under heating-cooling cycle tests are also revealed. Our work offers the referable method along with the decent parent material for further enhancement of TE performance, paving a possible route for the application and industrialization of Cu2-xSe TE materials.

It is challenging to achieve highly efficient thermoelectric materials due to the conflicts between thermopower (Seebeck coefficient) and electrical conductivity. These parameters are the core factors defining the thermoelectric property of any material. Here, we report the use of isovalent substitution as a tool to decouple the interdependency of the Seebeck coefficient and the electrical properties of cerium-doped bismuth selenide thermoelectric material. With this strategy, we can achieve a simultaneous increase in both the electrical conductivity and the Seebeck coefficient of the material by tuning the concentration of cerium doping, due to formation of neutral impurities and consequently the improvement of carrier mobility. Our theoretical calculation reveals a downward shift of the valence band with cerium concentration, which influences the thermoelectric enhancement of the synthesized materials. Finally, an order of magnitude enhancement of the figure of merit is obtained due to isovalent substitution, thus providing a new avenue for enhancing the thermoelectric performance of materials.

Clostridium difficileis an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficileinfection (CDI) is largely caused by two virulence factors, TcdA and TcdB. Here, we report a 3.87-Å-resolution crystal structure of TcdB holotoxin that captures a unique conformation of TcdB at endosomal pH. Complementary biophysical studies suggest that the C-terminal combined repetitive oligopeptides (CROPs) domain of TcdB is dynamic and can sample open and closed conformations that may facilitate modulation of TcdB activity in response to environmental and cellular cues during intoxication. Furthermore, we report three crystal structures of TcdB–antibody complexes that reveal how antibodies could specifically inhibit the activities of individual TcdB domains. Our studies provide novel insight into the structure and function of TcdB holotoxin and identify intrinsic vulnerabilities that could be exploited to develop new therapeutics and vaccines for the treatment of CDI. X-ray crystal structures of the full-length TcdB exotoxin of bacterial pathogen Clostridium difficilereveal pH-dependent conformational changes that allow translocation of the toxin from endosomes into the cytosol.

In order to explore efficient photocatalysts for N2reduction reaction (NRR), 0D AgInS2nanoparticles and 2D MXene (Ti3C2) nanosheets with different mass ratios are employed for building Z-scheme heterostructures. The resultant hybrids exhibit excellent interfacial charge transfer ability according to their optical and photo-electro properties. As a result, the obtained composite (30 wt% AgInS2) shows significant improvement on the photocatalytic performance for N2fixation with a high ammonia yield rate of 38.8 μmol/(g∙h) under visible-light illumination (>400 nm). Meanwhile, the DFT calculations show that the activation of N2in a dinuclear end-on bound structure could lead to high adsorption energy (Ead = −5.20 eV). Moreover, the mechanism of enhanced photocatalytic activity was proposed in terms of the quantum calculation between Ti3C2and N2. This work provides new systems for enhanced NRR performance.

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most frequently prescribed medications, their associated hypersensitivity reactions can not only lead to potentially severe reactions, but also limit analgesic and anti-inflammation options. This is especially true for those who are ailed with rheumatological or orthopaedic diseases leading to chronic pain and inflammatory conditions. This highlights the importance of identifying different types of NSAID hypersensitivity, and to find safe alternatives, namely selective COX-2 inhibitors, to groups of patients that may benefit the most from its utility.ObjectiveTo assess and categorise patients with suspected NSAID hypersensitivity, and to successfully provide alternatives to those with chronic rheumatologic and orthopedic ailments.Methods115 patients with suspected NSAID hypersensitivity were referred to Queen Mary Hospital for specialist evaluation between Jan 2023 and March 2024, those suitable were later challenged and delabelled. Remaining patients were assessed as clinically compatible with NSAID hypersensitivity, and later separated into whether they had background of orthopedic or rheumatological conditions, hence strong indications for NSAIDs, and without, to which selective COX-2 inhibitors tolerance tests were offered.ResultsOf 115 patients, 20% (23/115) were assessed as unlikely to have NSAID hypersensitivity, and later challenged. 18.2% (21/115) had negative challenges and were delabelled; only 2 patients had positive reactions, confirming NSAID hypersensitivity, of which symptoms were mild and did not require hospitalization. 82% of the remaining patients (94/115) were then later stratified into different NSAID hypersensitivity reactions according to European Academy of Allergy & Clinical Immunology (EAACI) guidelines. 57.3% (66/115) of patients were able to resume use of NSAIDs either by finding an alternative NSAID, namely a selective COX2 inhibitor (45/115, 39.1%), or through a negative drug challenge (21/115, 18.2%). Overall there was no significant difference in the proportion of patients with successful COX2 inhibitor challenges between the group with rheumatological and orthopedic diagnoses against those without (62% vs 54% p=0.414). 29 patients are still pending workup, likely underestimating the amount of patients that are able to resume NSAIDs.ConclusionNSAID hypersensitivity is amongst the most commonly reported drug allergies, and may present with many different clinical phenotypes. Patients with suspected NSAID hypersensitivity require allergist evaluation, and if not clinically suggestive of allergy, would benefit from drug challenges, especially in cases with underlying rheumatological or orthopedic conditions, where NSAIDs are essential. In situations where NSAID hypersensitivity is considered likely, selective COX-2 inhibitors can often be considered as a suitable alternative.

The lateral stalk of ribosomes constitutes the GTPase-associated center and is responsible for recruiting translation factors to the ribosomes. The eukaryotic stalk contains a P-complex, in which one molecule of uL10 (formerly known as P0) protein binds two copies of P1/P2 heterodimers. Unlike bacterial uL10, eukaryotic uL10 has an extended protuberant (uL10ext) domain inserted into the N-terminal RNA-binding domain. Here, we determined the solution structure of the extended protuberant domain of Bombyx moriuL10 by nuclear magnetic resonance spectroscopy. Comparison of the structures of the B. moriuL10ext domain with eRF1-bound and eEF2-bound ribosomes revealed significant structural rearrangement in a “hinge” region surrounding Phe183, a residue conserved in eukaryotic but not in archaeal uL10. 15N relaxation analyses showed that residues in the hinge region have significantly large values of transverse relaxation rates. To test the role of the conserved phenylalanine residue, we created a yeast mutant strain expressing an F181A variant of uL10. An in vitrotranslation assay showed that the alanine substitution increased the level of polyphenylalanine synthesis by ∼33%. Taken together, our results suggest that the hinge motion of the uL10ext domain facilitates the binding of different translation factors to the GTPase-associated center during protein synthesis.

The efficacy of providing self-acupressure educational materials in reducing stress and improving health-related quality of life (HRQOL) is uncertain. Evidence-based data to recommend for or against self-acupressure as an intervention for reducing stress and improving HRQOL is needed.

Dual-mode imaging combining photoacoustic and ultrasound modalities holds great promise for comprehensive tissue characterization. In traditional dual-mode imaging systems, however, the opaque ultrasound transducers are integrated in complex optical and ultrasound paths, leading to compromises in imaging efficiency and sensitivity. To address these challenges, we design and produce highly transparent Pb(Mg,Nb)O3PbTiO3ceramics with exceptional transparency of 68%, alongside a remarkable ultrahigh piezoelectric d33of 1500 pC/N. Leveraging this material, we fabricate a high-sensitivity transparent piezoelectric ultrasound transducer (TPUT) with a center frequency of 16 MHz and a bandwidth of 30%, which seamlessly integrating ultrasound and photoacoustic capabilities into one system to achieve simultaneous photoacoustic/ultrasound dual-mode imaging, showcasing a remarkable sensitivity for deep-tissue detection (e.g., 7.5 mm thick chicken breast meat). Additionally, invivophotoacoustic imaging of subcutaneous microvasculature in a mouse ear was successfully achieved via28 MHz TPUT. Our innovation not only advances imaging performance but also offers a cost-effective solution, paving the way for transformative biomedical imaging applications.