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.

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.

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.

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.

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.

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.

Calculation method of mean skin temperature weighted by temperature sensitivity of various parts of human body.

Skin temperature is an important physiological parameter, and its calculation methods are varied, and the results are different. At present, the area weighting method is mostly used to calculate the mean skin temperature. However, the skin of various parts of the human body has different degrees of sensitivity to temperature changes. Based on this, this article proposes two calculation methods using the weighting of the cold and heat sensitivity coefficients. This article conducted experiments with different ambient temperatures (18 °C/20 °C/22 °C), clothing thermal resistances (1.10 clo/1.31 clo/1.44 clo), and activity levels (sitting/standing/walking) to obtain the subjects' local skin temperature. And then compared and analyzed the calculation results of the above-mentioned two sensitivity coefficient methods and the traditional area weighting method. The results found that there is no significant difference between the two sensitivity coefficient methods proposed in this article (the absolute difference is up to 0.09 °C, and the relative difference is less than 0.4%), but there is a certain difference with the traditional area weighting method. The ANOVA shows that the deviation is mainly affected by the ambient temperature (P < 0.01), and the thermal resistance of clothing and activity level have no significant effects (P > 0.05). By studying the relationship between mean skin temperature and thermal sensation voting, it is found that when the human skin temperature changes due to environmental temperature changes, the mean skin temperature and thermal sensation calculated by new method have a higher linearity (correlation coefficient R2 > 0.92), and the slope is larger, which can better reflect the influence of thermal environment changes on the human body's thermal sensation.

Bi-Gaussian Stratified Wetting Model on Rough Surfaces.

Wetting mechanisms on rough surfaces were understood from either a monolayer or a multiscale perspective. However, it has recently been shown that the bi-Gaussian stratified nature of real surfaces should be accounted for when modeling mechanisms of lubrication, sealing, contact, friction, acoustic emission, and manufacture. In this work, a model combining Wenzel and Cassie theories was put forward to predict the static contact angle of a droplet on a bi-Gaussian stratified surface. The model was initially applied to numerically simulated surfaces and subsequently demonstrated on hydrophilic steel and hydrophobic self-assembled monolayer specimens with preset bi-Gaussian stratified topographies. In the Wenzel state, both the upper and the lower surface components are fully wetted. In the Cassie state, the upper component is still completely wetted, while the lower component serves as gas traps and reservoirs. By this model, wetting evolution was assessed, and the existence of different wetting states and potential state transitions was predicted.

Continuous graphene and carbon nanotube based high flexible and transparent pressure sensor arrays.

The transparent pressure sensing arrays durable to severe deformation are fabricated by covering the continuous graphene sheets on the tip of thermal plastic polyurethane (TPU) pyramids, while most of the TPU surface is covered by a layer of densely entangled single wall carbon nanotubes. The transparency of the conducting layer exceeds 91%. The capacitance variations between TPU surface and flat electrode under compressive deformation show high sensitivity and a broad dynamic range from hundreds Pa to MPa. The measured capacitance variations show high load sensitivity and stability under repeated deformation cycles. Finite element numerical simulations present that the contact area change under deformation increases the capacitance variation. The high stability of the capacitance response to fluctuated loads demonstrates that graphene layer on the surface of TPU pyramids maintains the continuity of electric contact under a large deformation ratio and high repeating cycles. 16 × 16 arrays are connected to a circuit and a typical load distribution is regenerated by mapping the local capacitance variations on the arrays with sub-minimeter spatial resolution.

[Clinicopathological diagnosis of IgG4-related disease: report of eight cases].

OBJECTIVE: To evaluate the clinical and pathological features of IgG4-related disease (IgG4RD). METHODS: The clinical data, laboratory profiles, radiological, pathological and therapeutic features of eight cases of IgG4RD were analyzed. This cohort included two cases of common bile duct and partial hepatectomy specimens, two of submandibular gland excision specimens, one from lung biopsy specimen, one from open lung biopsy specimen, one from renal biopsy specimen, and one from renal excision specimen. In all cases, adequate lesion tissues were obtained. They were paraffin embedded, HE stained, and additional special stains and immunohistochemistry performed (MaxVision method). RESULTS: This series consisted of five males and three females, with a mean age of onset of 60 years. Five cases were suspected to be malignant pre-operatively, including two cases suspected of common bile duct carcinoma, two suspected of salivary gland tumor, and one suspected of renal pelvic carcinoma. Elevated serum levels of IgG4 and IgE were detected in five cases and eosinophilia in four cases. Multi-organ involvement was noted in four cases. The major histopathological features associated with IgG4-RD were: dense lymphoplasmacytic infiltrate, with lymphoid follicle formation. Extensive eosinophilic infiltrate (> 10/HPF) was seen in four cases; fibrosis that was arranged at least focally in a storiform pattern was also noted. The numbers of IgG4 positive plasma cells were > 20-50/HPF, while the IgG4 to IgG ratio was more than 40%. Obliterative phlebitis was present in four cases. Other pathological changes such as necrotizing vasculitis or lymphoma were not found. Five patients responded well to glucocorticoids. CONCLUSIONS: IgG4RD has relatively specific histopathological features; accurate evaluation of the absolute and relative number of IgG4 positive plasma cells in lesional tissue, combining with clinical examination and exclusion of other causes of elevated IgG4, allows the diagnosis of IgG4RD. IgG4RD has complicated clinical manifestation, and glucocorticoids therapy is efficacious.

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.

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.

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.

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.

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.

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.

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.

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.

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.