Structural basis for the immune recognition and selectivity of the immune receptor PVRIG for ligand Nectin-2.

Nectin and nectin-like (Necl) co-receptor axis, comprised of receptors DNAM-1, TIGIT, CD96, PVRIG, and nectin/Necl ligands, is gaining prominence in immuno-oncology. Within this axis, the inhibitory receptor PVRIG recognizes Nectin-2 with high affinity, but the underlying molecular basis remains unknown. By determining the crystal structure of PVRIG in complex with Nectin-2, we identified a unique CC' loop in PVRIG, which complements the double-lock-and-key binding mode and contributes to its high affinity for Nectin-2. The association of the corresponding charged residues in the F-strands explains the ligand selectivity of PVRIG toward Nectin-2 but not for Necl-5. Moreover, comprehensive comparisons of the binding capacities between co-receptors and ligands provide innovative insights into the intra-axis immunoregulatory mechanism. Taken together, these findings broaden our understanding of immune recognition and regulation mediated by nectin/Necl co-receptors and provide a rationale for the development of immunotherapeutic strategies targeting the nectin/Necl axis.

NIR-Triggered Multifunctional NO Nanoplatform for Conquering Thermal Resistance in Biofilms.

Photothermal treatment (PTT) has emerged as a promising avenue for biofilm elimination, yet its potential drawbacks, such as local hyperpyrexia and bacterial heat resistance, have posed challenges. To address these concerns, an innovative nanoplatform (Au@mSiO2 -arg/ICG) is devised that integrates phototherapeutic and gas therapeutic functionalities. This multifaceted nanoplatform is composed of mesoporous silica-coated Au nanorods (Au@mSiO2 ), supplemented with l-arginine (l-arg) and indocyanine green (ICG), and is engineered for mild temperature PTT aimed at biofilm eradication. Au@mSiO2 -arg/ICG nanoparticles (NPs) show excellent antibacterial effects through the generation of nitric oxide (NO) gas, heat, and reactive oxygen species (ROS) under 808 nm light irradiation. The ROS generated by ICG initiates a cascade reaction with l-arg, ultimately yielding NO gas molecules. This localized release of NO not only effectively curbs the expression of heat shock proteins 70 mitigating bacterial thermoresistance, but also reduces extracellular polymeric substance allowing better penetration of the therapeutic agents. Furthermore, this nanoplatform achieves an outstanding biofilm elimination rate of over 99% in an abscess model under 808 nm light irradiation (0.8 W·cm-2 ), thereby establishing its potential as a dependable strategy for NO-enhanced mild PTT and antibacterial photodynamic therapy (aPDT) in clinical settings.

Spatial distribution characteristics of carbazole and polyhalogenated carbazoles in water column and sediments in the open Western Pacific Ocean.

Polyhalogenated carbazoles (PHCZs), an emerging persistent halogenated organic pollutant, have been detected in the environment. However, our understanding of PHCZs in the ocean remains limited. In this study, 47 seawater samples (covering 50 - 4000 m) and sediment samples (49 surface and 3 cores) were collected to investigate the occurrence and spatial distribution patterns of carbazole and its halogenated derivants (CZDs) in the Western Pacific Ocean. In seawater, the detection frequencies of CZ (97.87%) and 3-CCZ (57.45%) were relatively high. In addition, the average concentration of ΣPHCZs in the upper water (< 150 m, 0.23 ± 0.21 ng/L) was significantly lower than that in the deep ocean (1000 - 4000 m, 0.65 ± 0.56 ng/L, P < 0.05), which may indicate the vertical transport of PHCZs in the marine environment. The concentration of ΣCZDs in surface sediment ranges from 0.46 to 6.48 ng/g (mean 1.54 ng/g), among which CZ and 36-CCZ were the predominant components. Results from sediment cores demonstrate a noteworthy negative correlation between the concentration of CZDs and depth, indicating the ongoing natural degradation process occurring in sediment cores over a long period. This study offers distinctive insights into the occurrence, composition, and vertical features of CZDs in oceanic environments.

A versatile upconversion-based multimode lateral flow platform for rapid and ultrasensitive detection of microRNA towards health monitoring.

MicroRNAs are small single-stranded RNA molecules associated with gene expression and immune response, suggesting their potential as biomarkers for health monitoring. Herein, we designed a novel upconversion-based multimode lateral flow assay (LFA) system to detect microRNAs in body fluids by simultaneously producing three unique signals within a detection strip. The core-shell Au-DTNB@Ag nanoparticles act as both the Raman reporters and acceptors, quenching fluorescence from upconversion nanoparticles (UCNPs, NaYF4: Yb3+, Er3+) via the Förster resonance energy transfer mechanism. Using microRNA-21 as a representative analyte, the LFA system offers remarkable detection range from 2 nM to 1 fM, comparable to outcomes from signal amplification methods, due to the successful single-layer self-assembly of UCNPs on the NC membrane, which greatly enhances both the convenience and sensitivity of the LFA technique. Additionally, our proprietary fluorescence-Raman detection platform simplifies result acquisition by reducing procedural intricacies. The biosensor, when evaluated with diverse bodily fluids, showed remarkable selectivity and sustained stability. Importantly, our LFA biosensor effectively identified periodontitis and lung cancer patients from healthy subjects in genuine samples, indicating significant potential for disease prediction, early diagnosis, and progression tracking. This system holds promise as a multifunctional tool for various biomarker assays.

Rational design of a 'two-in-one' immunogen DAM drives potent immune response against mpox virus.

The global outbreak of the mpox virus (MPXV) in 2022 highlights the urgent need for safer and more accessible new-generation vaccines. Here, we used a structure-guided multi-antigen fusion strategy to design a 'two-in-one' immunogen based on the single-chain dimeric MPXV extracellular enveloped virus antigen A35 bivalently fused with the intracellular mature virus antigen M1, called DAM. DAM preserved the natural epitope configuration of both components and showed stronger A35-specific and M1-specific antibody responses and in vivo protective efficacy against vaccinia virus (VACV) compared to co-immunization strategies. The MPXV-specific neutralizing antibodies elicited by DAM were 28 times higher than those induced by live VACV vaccine. Aluminum-adjuvanted DAM vaccines protected mice from a lethal VACV challenge with a safety profile, and pilot-scale production confirmed the high yield and purity of DAM. Thus, our study provides innovative insights and an immunogen candidate for the development of alternative vaccines against MPXV and other orthopoxviruses.

Efficient and Stable Multicolor Emissions of the Coumarin-Modified Cs3LnCl6 Lead-Free Perovskite Nanocrystals and LED Application.

Lanthanide-based lead-free perovskite materials hold great promise for the development of high-resolution full-color displays in the future. Here, various Cs3LnCl6 perovskite nanocrystals (NCs) emitting light across the visible to near-infrared spectrum with remarkably high photoluminescence quantum yield (PLQY) are systemically prepared. Especially, by introducing multifunctional coumarin small molecules into Cs3EuCl6 NCs as an intermediate state, Cs3EuCl6 NCs can achieve an impressive PLQY of 92.4% with pure red emission and an exceptional energy transfer efficiency of nearly 93.2%. Furthermore, the lanthanide-based electroluminescent devices in red, green, and blue are successfully fabricated. Among them, the Cs3EuCl6-NC-based red light-emitting diode (LED) demonstrates a FWHM of 18 nm at 617 nm, an external quantum efficiency up to 5.17%, and a maximum brightness of 2373 cd m-2, which is the most excellent reported for lead-free narrowband (within 20 nm) emission devices. Notably, these devices exhibit an operating half-life of 440 h at a brightness level of 100 cd m-2, surpassing the performance of most reported lead-free perovskite LEDs (PLEDs). This work opens up exciting possibilities for the future commercialization of lanthanide-based PLEDs in the display industry, paving the way for more vibrant, energy-efficient, and long-lasting display technologies.

Investigation of rare earth-based magnetic nanocomposites for specific enrichment of exosomes from human plasma.

Exosomes, also known as small extracellular vesicles, are widely present in a variety of body fluids (e.g., blood, urine, and saliva). Exosomes are becoming an alternative promising source of diagnostic markers for disease rich in cargo of metabolites, proteins, and nucleic acids. However, due to the low abundance and structure similarity with protein complex, the efficient isolation of exosomes is one of the most important issues for biomedical applications. With a higher order of f-orbitals in rare earth element, it will have strong adsorption toward the phosphate group on the surface of the phospholipid bilayer of exosomes. In this study, we systematically investigated the ability of various rare earths interacting with phosphate-containing molecules and plasma exosomes. One of the best binding europium was selected and used to synthesize core-shell magnetic nanomaterials (Fe3O4@SiO2@Eu2O3) for the enrichment of exosomes from human plasma. The developed nanomaterials exhibited higher enrichment capacity, less time consumption and more convenient handling compared to commonly used ultracentrifugation method. The nanomaterials were applied to separate exosomes from the plasma of patients with hepatocellular carcinoma and healthy controls for metabolomics study with high-resolution mass spectrometry, where 70 differentially expressed metabolites were identified, involving amino acid and lipid metabolic pathway. We anticipated the rare earth-based materials to be an alternative approach on exosome isolation for disease diagnosis or postoperative clinical monitoring.

Using deep learning to accelerate magnetic resonance measurements of molecular exchange.

Real-time monitoring and quantitative measurement of molecular exchange between different microdomains are useful to characterize the local dynamics in porous media and biomedical applications of magnetic resonance. Diffusion exchange spectroscopy (DEXSY) is a noninvasive technique for such measurements. However, its application is largely limited by the involved long acquisition time and complex parameter estimation. In this study, we introduce a physics-guided deep neural network that accelerates DEXSY acquisition in a data-driven manner. The proposed method combines sampling pattern optimization and physical parameter estimation into a unified framework. Comprehensive simulations and experiments based on a two-site exchange system are conducted to demonstrate this new sampling optimization method in terms of accuracy, repeatability, and efficiency. This general framework can be adapted for other molecular exchange magnetic resonance measurements.

Highly hydrostable and flexible opal photonic crystal film for enhanced up-conversion fluorescence sensor of COVID-19 antibody.

Efficient detection of related markers is significant for the early screening of COVID-19. Near infrared (NIR) light excited up-conversion fluorescence probes are ideal for biosensing but limited by the low luminescence efficiency. In this work, a novel highly stable opal photonic crystal (OPC) structure was designed to provide an OPC effect for up-conversion fluorescence enhancement, and sensitive Novel Coronavirus IgG up-conversion FRET-based sensor was further constructed. For the problems of water stability and mechanical stability of polymer OPC which cannot be solved for a long time, polymer spray combined with a flipped OPC film strategy is presented. Fragmented size OPC film was firmly fixed by polymer modification layer, which gave large size OPC film great water stability, mechanical stability and bending performance without affecting the fluorescence enhancement property. On this basis, the up-conversion emission intensity was enhanced significantly, and fluorescence resonant energy transfer (FRET) based Novel Coronavirus IgG antibody sensor was constructed. Monolayer up-conversion nanoparticles (UCNPs) on the surface of the polydopamine (PDA)/OPC film can make the fluorescent signal more sensitive, and effectively reduce the detection limit. The test device integrating NIR excitation and mobile phone realized the visual fast detection, showing remarkable sensing performance for COVID-19 antibodies with the limit of detection (LOD) of 0.1 ng mL-1. This detection platform will provide a more effective tool for early detection of the novel coronavirus.

A Wearable Healthcare Platform Integrated with Biomimetical Ions Conducted Metal-Organic Framework Composites for Gas and Strain Sensing in Non-Overlapping Mode.

Intelligent wearable devices are essential for telemedicine healthcare as they enable real-time monitoring of physiological information. Elaborately constructing synapse-inspired materials provides a crucial guidance for designing high-performance sensors toward multiplex stimuli response. However, a realistic mimesis both in the "structure and sense" of biological synapses to obtain advanced multi-functions is still challenging but essential for simplifying subsequent circuit and logic programs. Herein, an ionic artificial synapse integrated with Ti3 CNTx nanosheets in situ grown with zeolitic imidazolate framework flowers (ZIF-L@Ti3 CNTx composite) is constructed to concurrently mimic the structure and working mechanism of the synapse. The flexible sensor of the bio-inspired ZIF-L@Ti3 CNTx composite exhibits excellent dual-mode dimethylamine (DMA) and strain-sensitive response with non-overlapping resistance variations. The specific ions conduction working principle triggered by DMA gas or strain with the assistance of humidity is confirmed by the density functional theory simulation. Last, an intelligent wearable system is self-developed by integrating the dual-mode sensor into flexible printed circuits. This device is successfully applied in pluralistic monitoring of abnormal physiological signals of Parkinson's sufferers, including real-time and accurate assessment of simulated DMA expiration and kinematic tremor signals. This work provides a feasible routine to develop intelligent multifunctional devices for upsurging telemedicine diagnosis.

Overall thermal sensation and comfort prediction with different model combinations: Cold and hot step-change environments in winter.

Currently, numerous thermal comfort models have been proposed; however, research on the combination of different models is lacking. This study aims to predict the overall thermal sensation (OTS*) and thermal comfort (OTC*) with different model combinations under hot and cold step changes. Three cold- and hot-shock processes are designed in the climate chamber. Accordingly, the skin temperature, thermal sensation, and thermal comfort votes of 16 participants are collected. The impacts of winter hot and cold step changes on subjective votes and skin temperatures are evaluated. Further, the OTS* and OTC* values are calculated, and their accuracy under different model combinations is analyzed. The results reveal that thermal sensation changes in human body exhibit distinct asymmetry under the cold and hot step-changes, except for the cycle of "15-30-15 °C" (I15). The parts farther from the core area become more asymmetrical after the step changes. The single models exhibit the highest accuracy in different model combinations. The combined form of a single model is recommended for thermal sensation or comfort prediction.

Opal photonic crystal-enhanced upconversion turn-off fluorescent immunoassay for salivary CEA with oral cancer.

The point-of-care test of tumor markers in saliva with high specificity and sensitivity for early diagnosis of oral cancer is of great interest and significance, but remaining a daunting challenge due to the low concentration of such biomarkers in oral fluid. Herein, a turn-off biosensor based on opal photonic crystal (OPC) enhanced upconversion fluorescence is proposed to detect the carcinoembryonic antigen (CEA) in saliva by applying fluorescence resonance energy transfer sensing strategy. Hydrophilic PEI ligands are modified on upconversion nanoparticles to enhance the sensitivity of biosensor by promoting sufficient contact between saliva and detection region. As a substrate for the biosensor, OPC can also provide a local-field effect for greatly enhanced upconversion fluorescence by coupling the stop band and excitation light, and a 66-fold amplification of the upconversion fluorescence signal was obtained. For the CEA detection in spiked saliva, such sensors showed a favorable linear relationship at 0.1-2.5 ng mL-1 and more than 2.5 ng mL-1, respectively. The limit of detection was down to 0.1 ng mL-1. Moreover, by monitoring real saliva, the effective discrepancy between patients and healthy people was confirmed, indicating remarkable practical application value in clinical early diagnosis and home-based self-monitoring of tumors.

Association between thermal response and endogenous dopamine: Step-change environments in winter.

Temperature step change is the typical transient thermal environment. The purpose of this study was to explore the association of subjective and objective parameters in a step-change environment, including thermal sensation vote (TSV), thermal comfort vote (TCV), mean skin temperature (MST) and endogenous dopamine (DA). Three temperature step changes defined as I3 (15 °C-18 °C to 15 °C), I9 (15 °C-24 °C to 15 °C) and I15 (15 °C-30 °C to 15 °C) were designed for this experiment. Eight male and eight female healthy subjects who participated in the experiment reported thermal perception (TSV and TCV). Skin temperatures of six body parts and DA were measured. Results show that the inverted U-shaped in TSV and TCV was deviated by seasonal factors of the experiment. The deviation direction of TSV in winter was to the warm sensation side, which was opposite to the inherent cold and hot impression of people in winter and summer. The association between dimensionless dopamine (DA*), TSV and MST were described as follows: DA* was the U-shaped change with exposure times when MST was not greater than 31 °C, and TSV was at -2 and -1, and DA* increased with exposure times when MST was greater than 31 °C, and TSV was at 0, 1 and 2. The changes in the body heat storage and autonomous thermal regulation under temperature step changes may potentially be related to the concentration of DA. The human state on thermal nonequilibrium and stronger thermal regulation would correspond to a higher concentration of DA. This work is conducive to exploring the human regulation mechanism in a transient environment.

Influence of microplastics on microbial anaerobic detoxification of chlorophenols.

Microplastics (MPs) can absorb halogenated organic compounds and transport them into marine anaerobic zones. Microbial reductive dehalogenation is a major process that naturally attenuates organohalide pollutants in anaerobic environments. Here, we aimed to determine the mechanisms through which MPs affect the microbe-mediated marine halogen cycle by incubating 2,4,6-trichlorophenol (TCP) dechlorinating cultures with various types of MPs. We found that TCP was dechlorinated to 4-chlorophenol in biotic control and polypropylene (PP) cultures, but essentially terminated at 2,4-dichlorophenol in polyethylene (PE) and polyethylene terephthalate (PET) cultures after incubation for 20 days. Oxygen-containing functional groups such as peroxide and aldehyde were enriched on PE and PET after incubation and corresponded to elevated levels of intracellular reactive oxygen species (ROS) in the microorganisms. Adding PE or PET to the cultures exerted limited effects on hydrogenase and ATPase activities, but delayed the expression of the gene encoding reductive dehalogenase (RDase). Considering the limited changes in the microbial composition of the enriched cultures, these findings suggested that microbial dechlorination is probably affected by MPs through the ROS-induced inhibition of RDase synthesis and/or activity. Overall, our findings showed that extensive MP pollution is unfavorable to environmental xenobiotic detoxification.

Carbazole and polyhalogenated carbazoles in the marine environment around the Zhoushan Archipelago: Distribution characteristics, environmental behavior, and sources.

The distribution characteristics and drivers of carbazole (CZ) and polyhalogenated carbazoles are still poorly understood. In this study, 96 samples were collected around the Zhoushan Archipelago, and their distribution characteristics were assessed. The results showed that CZ, 36-CCZ, and 36-BCZ were the top three abundant congeners in most collected samples. The bioaccumulation analysis revealed that marine plants prefer to accumulate CZ and bromocarbazoles rather than chlorocarbazoles. Both the mean concentrations of total carbazole and its derivants (ΣCZDs), as well as individual congeners, are the highest in sediments around the berthing areas of cargo ships and oil tankers. Meanwhile, ΣCZDs of these sediments are significantly influenced by the geo-weighted displacement of ships (r = 0.61; p < 0.05), indicating the ballast water from these ships as potential contributor for marine CZDs. Moreover, the accumulation of CZ in plankton, planktonic origin of sedimentary organic matter, and relationship between CZ and C/N ratio (p < 0.05) in sediments support the scenario that plankton absorbs and takes CZ into the sediments. These findings will promote the understanding of the sources, environmental behaviors, and fates of marine CZDs.

Extending the Incidence Angle of Shear Vertical Wave Electromagnetic Acoustic Transducer with Horizontal Magnetization.

Angled shear vertical (SV) waves have been successfully employed in the non-destructive testing of welds, pipes, and railways. Non-contact meander-line coil electromagnetic acoustic transducers (EMAT) have many benefits in generating angled SV waves. The most important benefit is that the incidence angle of an SV wave can be controlled by the excitation frequency. However, the incidence angle of a traditional SV-wave EMAT is reported to be under 45 degrees in many cases. In this work, such cases are tested, and the problems of the received signal at large incidence angles are found to be due to wave interference and small signal amplitudes. An equivalent finite element (FE) model is established to analyze the problem, and the main reason is found to be the head wave. An alternative configuration of angled SV-wave EMAT with horizontal magnetization is proposed to reduce the influence of the head wave. Finally, the results from simulations and experiments show that the proposed EMAT has a larger signal amplitude and significantly reduced interference in large-incidence angle scenarios. Moreover, an incidence angle of an SV wave of up to 60 degrees can be achieved, which will help improve the performance and capability of nondestructive testing.

Antibacterial PDT nanoplatform capable of releasing therapeutic gas for synergistic and enhanced treatment against deep infections.

Antibacterial photodynamic therapy (aPDT) has emerged as an attractive treatment option for efficient removal of pathogenic bacteria. However, aPDT in deep tissue will encounter difficulties such as limited light penetration depth, insufficient oxygen (O2) supply and inability to eliminate inflammation introduced by bacteria, which hinders its clinical application. Herein, the near infrared (NIR) strategy of simultaneously generating O2 and CO was developed for aPDT based antibacterial therapy and mitigation of deep infection inflammation. Methods: We prepared NIR-mediated multifunctional aPDT nanoplatform (POS-UCNPs/ICG) producing therapeutic gas of O2 and CO. The CO, O2 and ROS generation of the nanoplatform were characterized by dye probes, respectively. The antibacterial activity and anti-inflammation of POS-UCNPs/ICG were demonstrated in vitro and in vivo. In addition, the therapeutic effects in vivo were serially analyzed by immunofluorescence staining, Masson's staining, hematoxylin and eosin staining, colony formation units (CFU) and so on. Results: NIR-mediated multifunctional aPDT nanoplatform was realized by combining the up-conversion nanoparticles (UCNPs) and partially oxidized SnS2 (POS) nanosheets (NSs) as well as indocyanine green (ICG). Using a single 808 nm light, aPDT can be achieved via ICG molecules, meanwhile, O2/CO can be generated by POS NSs through upconversion light excitation. During the aPDT process, O2 can enhance aPDT, while CO can regulate inflammation through the PI3K/NF-κB pathway. Therefore, POS-UCNPs/ICG groups had a highest percentage of healing area up to 91.55±1.26% in mouse abscess model. Conclusion: Due to enhanced aPDT and anti-inflammatory collaborative therapy, the POS-UCNPs/ICG composites showed remarkably accelerated recovery in animal abscess models. Such NIR light responsive nanoplatform with optimized antibacterial capacity and immunomodulatory functions is promising for clinical therapeutics of bacteria-induced infections.

Photonic Crystal Effects on Upconversion Enhancement of LiErF4:0.5%Tm3+@LiYF4 for Noncontact Cholesterol Detection.

Cholesterol is a vital compound in maintenance for human health, and its concentration levels are tightly associated with various diseases. Therefore, accurate monitoring of cholesterol is of great significance in clinical diagnosis. Herein, we fabricated a noncontact biosensor based on photonic crystal-enhanced upconversion nanoparticles (UCNPs) for highly sensitive and interference-free cholesterol detection. By compounding LiErF4:0.5%Tm3+@LiYF4 UCNPs with poly(methyl methacrylate) (PMMA) photonic crystals (OPCs), we were able to selectively tune the coupling of the photonic band gap to the excitation field and modulate the upconversion (UC) luminescence intensity, given the unique multi-wavelength excitation property of LiErF4:0.5%Tm3+@LiYF4. A 48.5-fold enhancement of the monochromatic red UC emission was ultimately achieved at 980 nm excitation, ensuring improved detection sensitivity. Based on the principle of quenching of the intense monochromic red UC emission by the oxidation products of 3,3',5,5'-tetramethylbenzidine (TMB) yielded from the cholesterol cascade reactions, the biosensor has a detection limit of 1.6 µM for cholesterol with excellent specificity and stability. In addition, the testing results of the as-designed biosensor in patients are highly consistent with clinical diagnostic data, providing a sensitive, reliable, reusable, interference-free, and alternative strategy for clinical cholesterol detection.

Ni2+ and Pr3+ Co-doped CsPbCl3 perovskite quantum dots with efficient infrared emission at 1300 nm.

Lead halide perovskite quantum dots (PQDs) show great prospects in the field of optoelectronic applications. Although having high efficiency and narrow-band emission performance in the visible light region, the infrared multicolor luminescence performance of perovskite nanocrystals is still highly desired. In this work, in order to increase the luminescence intensity and extend the infrared multicolor luminescence, transition metal and rare earth ions are co-doped into PQDs. Herein, PQDs emitting at 1300 nm are realized by Pr3+ doping, which has not been reported in previous literature. The luminescence and kinetic process of Ni2+ and Pr3+ co-doped CsPbCl3 PQDs are studied, which exhibit considerably enhanced emission intensity at 400 nm and 1300 nm, with an overall quantum efficiency of photoluminescence (PLQY) of 89% and the highest infrared PLQY of 23%.