Peripheral Blood Lymphocyte Subsets and Heterogeneity of B Cell Subsets in Patients of Idiopathic Inflammatory Myositis with Different Myositis-specific Autoantibodies.

Idiopathic inflammatory myopathies (IIM) are a group of myopathies that present with muscle weakness and multiple extra-muscular manifestations, in which lymphocytes play central roles in myositis pathogenesis. This study aimed to explore the clinical characteristics of lymphocyte subsets, especially B cell subsets, in patients with IIM. Our study included 176 patients with active IIM and 210 gender/age-matched healthy controls (HCs). Compared to HCs, patients have reduced counts of T cells, B cells, and natural killer cells. In addition, B cell subsets from 153 patients with IIM and 92 HCs were characterized. Patients had a lower percentage of memory B cells and translational memory B cells, while those patients were with an elevated percentage of CD19+ B cells, plasmablast and naïve B cells compared with HCs. Moreover, to further explore the heterogeneity of B cells in IIM, patients were categorized into three clusters based on clustering analysis. Cluster 1 was dominated by CD19+ B cells, Bregs and naïve B cells, cluster 3 was dominated by memory B cells and plasmablast, and cluster 2 had the highest proportion of translational memory B cells. Notably, patients in cluster 1 presented with higher CK levels, indicating muscle damage, whereas patients in cluster 3 showed a higher incidence of chest tightness. Our study indicated that lymphopenia is a common manifestation in patients with IIM. B cell subsets are abnormally expressed and showed high heterogeneity in patients with IIM. The patients with IIM were divided into three different clusters with different percentages of chest tightness and distinct CK levels.

Lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation.

Ultrasound-driven bioelectronics could offer a wireless scheme with sustainable power supply; however, current ultrasound implantable systems present critical challenges in biocompatibility and harvesting performance related to lead/lead-free piezoelectric materials and devices. Here, we report a lead-free dual-frequency ultrasound implants for wireless, biphasic deep brain stimulation, which integrates two developed lead-free sandwich porous 1-3-type piezoelectric composite elements with enhanced harvesting performance in a flexible printed circuit board. The implant is ultrasonically powered through a portable external dual-frequency transducer and generates programmable biphasic stimulus pulses in clinically relevant frequencies. Furthermore, we demonstrate ultrasound-driven implants for long-term biosafety therapy in deep brain stimulation through an epileptic rodent model. With biocompatibility and improved electrical performance, the lead-free materials and devices presented here could provide a promising platform for developing implantable ultrasonic electronics in the future.

Optimizing ultrashort pulse in fiber laser based on artificial intelligence algorithm.

Ultrashort pulses, characterized by their short pulse duration, diverse spectral content, and high peak power, are widely used in fields including laser processing, optical storage, biomedical sciences, and laser imaging. The complex, highly-nonlinear process of ultrashort pulse evolution within fiber lasers is influenced by numerous aspects such as dispersion, loss, gain, and nonlinear effects. Traditionally, the split-step Fourier transforms method is employed for simulating ultrashort pulses in fiber lasers, which involves traversing multiple parameters within the fiber to attain the pulse's optimal state. The simulation is a significantly time-consuming process. Here, we use a neural network model to fit and predict the impact of multiple parameters on the pulse characteristics within fiber lasers, enabling parameter optimization through genetic algorithms to determine the optimal pulse duration, pulse energy, and peak power. Integrating artificial intelligence algorithms simplifies the acquisition of optimal pulse parameters and enhances our understanding of multiple parameters' impact on the pulse characteristics. The investigation of ultrashort pulse optimization based on artificial intelligence holds immense potential for laser design.

Harvesting Vibration Energy for Efficient Cocatalyst-Free Sonocatalytic H2 Production over Magnetically Separable Ultra-Low-Cost Fe3O4.

The cavitation effect is an important geochemical phenomenon, which generally exists under strong hydrodynamic conditions. Therefore, developing an economical and effective sonocatalyst becomes a vital method in capitalizing on the cavitation effect for energy generation. In this study, we first report a novel Fe3O4 sonocatalyst that can be easily separated using a magnetic field and does not require any additional cocatalysts for H2 production from H2O. When subjected to ultrasonic vibration, this catalyst achieves an impressive H2 production rate of up to 175 µmol/h/USD (where USD stands for dollars), surpassing most previously reported mechanical catalytic materials. Furthermore, the ease and efficiency of separating this catalyst using an external magnetic field, coupled with its effortless recovery, highlight its significant potential for practical applications. By addressing the key limitations of conventional sonocatalysts, our study not only demonstrates the feasibility of using Fe3O4 as a highly efficient sonocatalyst but also showcases the exciting possibility of using a new class of magnetically separable sonocatalysts to productively transform mechanical energy into chemical energy.

The effect analysis of shape design of different charging piles based on Human physiological characteristics using the MF-DFA.

With the rapid development of new energy vehicles, the users have an increasing demand for charging piles. It is generally believed that the charging pile is a kind of practical product, and it only needs to realize the charging function. However, as a product, the shape design of the charging pile will directly affect the user experience, thus affecting product sales. Therefore, in the face of increasingly fierce market competition, when designing the shape of charging piles, it is necessary to adopt the traditional evaluation method and human physiological cognitive characteristics to evaluate the shape of charging piles more objectively. From the user's point of view, using the electroencephalogram (EEG) of the user, with the help of the multifractal detrended fluctuation analysis (MF-DFA) method, this paper comprehensively analyzes the differences in emotional cognitive characteristics between two kinds of charging piles, namely, the charging pile with a curved appearance design and the charging pile with square appearance design. The results show that there are significant differences in human physiological cognitive characteristics between two kinds of charging piles with different shapes. And different shapes of charging piles have different physiological cognitive differences for users. When designing charging pile product shapes, human beings can objectively evaluate the product shape design according to the physiological cognition differences of users, so as to optimize the charging pile product shape design.

Health risks and sources of trace elements and black carbon in PM2.5 from 2019 to 2021 in Beijing.

A comprehensive health risk assessment of PM2.5 is meaningful to understand the current status and directions regarding further improving air quality from the perspective of human health. In this study, we evaluated the health risks of PM2.5 as well as highly toxic inorganic components, including heavy metals (HMs) and black carbon (BC) based on long-term observations in Beijing from 2019 to 2021. Our results showed that the relative risks of chronic obstructive pulmonary disease, lung cancer, acute lower respiratory tract infection, ischemic heart disease, and stroke decreased by 4.07%-9.30% in 2020 and 2.12%-6.70% in 2021 compared with 2019. However, they were still at high levels ranging from 1.26 to 1.77, in particular, stroke showed the highest value in 2021. Mn had the highest hazard quotient (HQ, from 2.18 to 2.56) for adults from 2019 to 2021, while Ni, Cr, Pb, As, and BC showed high carcinogenic risks (CR > 1.0×10-6) for adults. The HQ values of Mn and As and the CR values of Pb and As showed constant or slight upwards trends during our observations, which is in contrast to the downward trends of other HMs and PM2.5. Mn, Cr, and BC are crucial toxicants in PM2.5. A significant shrink of southern region sourcesof HMs and BCshrank suggests the increased importance of local sources. Industry, dust, and biomass burning are the major contributors to the non-carcinogenic risks, while traffic emissions and industry are the dominant contributors to the carcinogenic risks in Beijing.

Printing 3D Metallic Structures in Porous Matrix.

The fabrication of metallic micro/nanostructures has great potential for advancing optoelectronic microdevices. Over the past decade, femtosecond laser direct writing (FsLDW) technology has played a crucial role in driving progress in this field. In this study, silica gel glass is used as a supporting medium, and FsLDW is employed to reduce gold and palladium ions using 7-Diethylamino-3-thenoylcoumarin (DETC) as a two-photon sensitizer, enabling the printing of conductive multilayered and 3D metallic structures. How the pore size of the silica gel glass affects the electrical conductivity of printed metal wires is systematically examined. This 3D printing method is versatile and offers expanded opportunities for applying metallic micro/nanostructures in optoelectronic devices.

The Significant Role of New Particle Composition and Morphology on the HNO3-Driven Growth of Particles down to Sub-10 nm.

New particle formation and growth greatly influence air quality and the global climate. Recent CERN Cosmics Leaving OUtdoor Droplets (CLOUD) chamber experiments proposed that in cold urban atmospheres with highly supersaturated HNO3 and NH3, newly formed sub-10 nm nanoparticles can grow rapidly (up to 1000 nm h-1). Here, we present direct observational evidence that in winter Beijing with persistent highly supersaturated HNO3 and NH3, nitrate contributed less than ∼14% of the 8-40 nm nanoparticle composition, and overall growth rates were only ∼0.8-5 nm h-1. To explain the observed growth rates and particulate nitrate fraction, the effective mass accommodation coefficient of HNO3 (αHNO3) on the nanoparticles in urban Beijing needs to be 2-4 orders of magnitude lower than those in the CLOUD chamber. We propose that the inefficient uptake of HNO3 on nanoparticles is mainly due to the much higher particulate organic fraction and lower relative humidity in urban Beijing. To quantitatively reproduce the observed growth, we show that an inhomogeneous "inorganic core-organic shell" nanoparticle morphology might exist for nanoparticles in Beijing. This study emphasized that growth for nanoparticles down to sub-10 nm was largely influenced by their composition, which was previously ignored and should be considered in future studies on nanoparticle growth.

Mild synthesis of ultra-bright carbon dots with solvatochromism for rapid lipid droplet monitoring in varied physiological processes.

Lipid droplets (LDs) participating in various cellular activities and are increasingly being emphasized. Fluorescence imaging provides powerful tool for dynamic tracking of LDs, however, most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield (PLQY), poor photostability and tedious washing procedures. Herein, a novel yellow-emissive carbon dot (OT-CD) has been synthesized conveniently with high PLQY up to 90%. Besides, OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2, which is much higher than most LDs probes. These characters enable OT-CD high brightness, stable and wash-free LDs probing, and feasible for in vivo imaging. Then, detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded, including ferroptosis and other diseases processes. Furthermore, fast whole imaging of zebrafish and identified LD enrichment in injured liver indicate its further feasibility for in vivo application. In contrast to the reported studies to date, this approach provides a versatile conventional synthesis system for high-performance LDs targeting probes, combing the advantages of easy and high-yield production, as well as robust brightness and stability for long-term imaging, facilitating investigations into organelle interactions and LD-associated diseases.

Transient breathing dynamics during extinction of dissipative solitons in mode-locked fiber lasers.

The utilization of the dispersive Fourier transformation approach has enabled comprehensive observation of the birth process of dissipative solitons in fiber lasers. However, there is still a dearth of deep understanding regarding the extinction process of dissipative solitons. In this study, we have utilized a combination of experimental and numerical techniques to thoroughly examine the breathing dynamics of dissipative solitons during the extinction process in an Er-doped mode-locked fiber laser. The results demonstrate that the transient breathing dynamics have a substantial impact on the extinction stage of both steady-state and breathing-state dissipative solitons. The duration of transient breathing exhibits a high degree of sensitivity to variations in pump power. Numerical simulations are utilized to produce analogous breathing dynamics within the framework of a model that integrates equations characterizing the population inversion in a mode-locked laser. These results corroborate the role of Q-switching instability in the onset of breathing oscillations. Furthermore, these findings offer new possibilities for the advancement of various operational frameworks for ultrafast lasers.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCCs) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3. The former group exhibits reduced proliferation, genome instability, and heightened sensitivity to genotoxic agents like PARP1/2 inhibitors. Conversely, H3K36M HNSCC models with constant H3K27me3 levels lack these characteristics unless H3K27me3 is elevated by DNA hypomethylating agents or inhibiting H3K27me3 demethylases KDM6A/B. Mechanistically, H3K36M reduces H3K36me by directly impeding the activities of the histone methyltransferase NSD3 and the histone demethylase LSD2. Notably, aberrant H3K27me3 levels induced by H3K36M expression are not a bona fide epigenetic mark because they require continuous expression of H3K36M to be inherited. Moreover, increased sensitivity to PARP1/2 inhibitors in H3K36M HNSCC models depends solely on elevated H3K27me3 levels and diminishing BRCA1- and FANCD2-dependent DNA repair. Finally, a PARP1/2 inhibitor alone reduces tumor burden in a H3K36M HNSCC xenograft model with elevated H3K27me3, whereas in a model with consistent H3K27me3, a combination of PARP1/2 inhibitors and agents that up-regulate H3K27me3 proves to be successful. These findings underscore the crucial balance between H3K36 and H3K27 methylation in maintaining genome instability, offering new therapeutic options for patients with H3K36me-deficient tumors.

Are 4f-Orbitals Engaged in Covalent Bonding Between Lanthanides and Triphenylphosphine Oxide? An Oxygen K-Edge X-ray Absorption Spectroscopy and Density Functional Theory Study.

The bonding covalency between trivalent lanthanides (Ln = La, Pr, Nd, Eu, Gd) and triphenylphosphine oxide (TPPO) is studied by X-ray absorption spectra (XAS) and density functional theory (DFT) calculations on the LnCl3(TPPO)3 complexes. The O, P, and Cl K-edge XAS for the single crystals of LnCl3(TPPO)3 were collected, and the spectra were interpreted based on DFT calculations. The O and P K-edge XAS spectra showed no significant change across the Ln series in the LnCl3(TPPO)3 complexes, unlike the Cl K-edge XAS spectra. The experimental O K-edge XAS spectra suggest no mixing between the Ln 4f- and the O 2p-orbitals in the LnCl3(TPPO)3 complexes. DFT calculations indicate that the amount of the O 2p character per Ln-O bond is less than 0.1% in the Ln 4f-based orbitals in all of the LnCl3(TPPO)3 complexes. The experimental spectra and theoretical calculations demonstrate that Ln 4f-orbitals are not engaged in the covalent bonding of lanthanides with TPPO, which contrasts the involvement of U 5f-orbitals in covalent bonding in the UO2Cl2(TPPO)2 complex. Results in this work reinforce our previous speculation that bonding covalency is potentially responsible for the extractability of monodentate organophosphorus ligands toward metal ions.

Epigenetic mechanisms driving the pathogenesis of systemic lupus erythematosus, systemic sclerosis and dermatomyositis.

Autoimmune connective tissue disorders, including systemic lupus erythematosus, systemic sclerosis (SSc) and dermatomyositis (DM), often manifest with debilitating cutaneous lesions and can result in systemic organ damage that may be life-threatening. Despite recent therapeutic advancements, many patients still experience low rates of sustained remission and significant treatment toxicity. While genetic predisposition plays a role in these connective tissue disorders, the relatively low concordance rates among monozygotic twins (ranging from approximately 4% for SSc to about 11%-50% for SLE) have prompted increased scrutiny of the epigenetic factors contributing to these diseases. In this review, we explore some seminal studies and key findings to provide a comprehensive understanding of how dysregulated epigenetic mechanisms can contribute to the development of SLE, SSc and DM.

Structural and energetic insights into the selective inhibition of PKMYT1 against WEE1.

Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the WEE family and responsible for the regulation of CDK1 phosphorylation, has been considered a promising therapeutic target for cancer therapy. However, the highly structural conservation of the ATP-binding sites of the WEE family poses a challenge to the design of selective inhibitors for PKMYT1. Here, molecular docking, multiple microsecond-length molecular dynamics (MD) simulations and end-point free energy calculations were performed to uncover the molecular mechanism of the binding selectivity of RP-6306 toward PKMYT1 over its highly homologous kinase WEE1. The binding specificity of RP-6306 reported in previous experimental bioassays was clarified by MD simulations and binding free energy calculations. Further, the binding free energy prediction indicated that the binding selectivity of RP-6306 largely derived from the difference in the protein-ligand electrostatic interactions. The per-residue free energy decomposition suggested that the non-conserved gatekeeper residue in the hinge domain of PKMYT1/WEE1, Thr187/Asn376, is the critical factor responsible for the binding selectivity of RP-6306 toward PKMYT1. In addition, a water-mediated hydrogen bond was formed between RP-6306 and Gly191 at the hinge domain in the PKMYT1/RP-6306 complex, which was absent in the WEE1/RP-6306 complex. This study is expected to offer useful information for the design of more potent and selective PKMYT1 inhibitors.Communicated by Ramaswamy H. Sarma.

The Promising Seesaw Relationship Between Activity and Stability of Ru-Based Electrocatalysts for Acid Oxygen Evolution and Proton Exchange Membrane Water Electrolysis.

The development of electrocatalysts that are not reliant on iridium for efficient acid-oxygen evolution is a critical step towards the proton exchange membrane water electrolysis (PEMWE) and green hydrogen industry. Ruthenium-based electrocatalysts have garnered widespread attention due to their remarkable catalytic activity and lower commercial price. However, the challenge lies in balancing the seesaw relationship between activity and stability of these electrocatalysts during the acid-oxygen evolution reaction (OER). This review delves into the progress made in Ru-based electrocatalysts with regards to acid OER and PEMWE applications. It highlights the significance of customizing the acidic OER mechanism of Ru-based electrocatalysts through the coordination of adsorption evolution mechanism (AEM) and lattice oxygen oxidation mechanism (LOM) to attain the ideal activity and stability relationship. The promising tradeoffs between the activity and stability of different Ru-based electrocatalysts, including Ru metals and alloys, Ru single-atomic materials, Ru oxides, and derived complexes, and Ru-based heterojunctions, as well as their applicability to PEMWE systems, are discussed in detail. Furthermore, this paper offers insights on in situ control of Ru active sites, dynamic catalytic mechanism, and commercial application of PEMWE. Based on three-way relationship between cost, activity, and stability, the perspectives and development are provided.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCC) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3. The first group shows decreased proliferation, genome instability, and increased sensitivity to genotoxic agents, such as PARP1/2 inhibitors. In contrast, the H3K36M HNSCC models with steady H3K27me3 levels do not exhibit these characteristics unless H3K27me3 levels are elevated, either by DNA hypomethylating agents or by inhibiting the H3K27me3 demethylases KDM6A/B. Mechanistically, we found that H3K36M reduces H3K36me by directly impeding the activities of the histone methyltransferase NSD3 and the histone demethylase LSD2. Notably, we found that aberrant H3K27me3 levels induced by H3K36M expression is not a bona fide epigenetic mark in HNSCC since it requires continuous expression of H3K36M to be inherited. Moreover, increased sensitivity of H3K36M HNSCC models to PARP1/2 inhibitors solely depends on the increased H3K27me3 levels. Indeed, aberrantly high H3K27me3 levels decrease BRCA1 and FANCD2-dependent DNA repair, resulting in higher sensitivity to DNA breaks and replication stress. Finally, in support of our in vitro findings, a PARP1/2 inhibitor alone reduce tumor burden in a H3K36M HNSCC xenograft model with elevated H3K27me3, whereas in a H3K36M HNSCC xenograft model with consistent H3K27me3 levels, a combination of PARP1/2 inhibitors and agents that upregulate H3K27me3 proves to be successful. In conclusion, our findings underscore a delicate balance between H3K36 and H3K27 methylation, essential for maintaining genome stability. This equilibrium presents promising therapeutic opportunities for patients with H3K36me-deficient tumors.

Soliton interaction in a MXene-based mode-locked fiber laser.

MXenes are a class of two-dimensional layered structure ternary metal carbide or/and nitride materials. Recently, the MXene V2CTx has demonstrated excellent long-term stability, strong saturable absorption, and fast optical-switching capability, used to generate Q-switched and ultrashort pulsed lasers. However, bound-state fiber lasers based on V2CTx have not been reported yet. In this study, V2CTx is combined with a D-shaped fiber to form a saturable absorber device, whose modulation depth is measured to be 1.6%. By inserting the saturable absorber into an Er-doped fiber laser, bound states with different soliton separation and munbers are successfully obtained. Additionally, bound states with a compound soliton structure, such as the (2 + 2)- and (2 + 1)-type, are also realized. Our findings show that V2CTx can be developed as an efficient ultrafast photonics candidate to further understand the complex nonlinear dynamics of bound-state pulses in fiber lasers.

Photochemically deoxygenating micelles for protecting TTA-UC against oxygen quenching.

Pluronic F127, P123 and cross-linked F127 diacrylate micelles are photochemically deoxygenating nanocapsules in which oxygen could be removed by photochemical reaction with a surfactant and efficient triplet-triplet annihilation photon upconversion (TTA-UC) can be achieved in air. The efficiency of TTA-UC under air is comparable to that under deoxygenated conditions.

Spatiotemporal profile and ecological impacts of major and trace elements in surface sediments of marginal seas of the Arctic and Northern Pacific Oceans.

The status and ecological impacts of sedimentary elements of the marginal seas of Arctic and Northern Pacific Oceans was investigated during 2016 to 2018 by using inductively coupled plasma mass spectrometry. Industrial (0.006 mg kg-1-64.6 g kg-1), precious (0.003-43.8 mg kg-1), rare earth (0.006-112.9 mg kg-1), and heavy metal (0.009-398.9 mg kg-1) elements showed spatial variation, and temporal uniformity. The results indicated ΣREEs and light REEs enrichment compared to chondrite and heavy REEs, respectively, while nonsignificant positive and negative δCe and δEu anomalies existed, respectively. High contamination and extreme enrichment of priority control, industrial (As, Mo, Re, Sb), precious (Au, Ir, Pd, Pt, and Ru) and RE elements indicated potential moderate to high ecological and biological risks. The study highlighted the ecological importance and fragile nature of these ecosystems and calls for an urgent action to ensure sustainability of these ecosystems.

In Situ Decoration of Bi2S3 Nanosheets on Zinc Oxide/Cellulose Acetate Composite Films for Photodegradation of Dyes under Visible Light Irradiation.

A novel Bi2S3-zinc oxide/cellulose acetate composite film was prepared through a blending-wet phase conversion and in situ precipitate method. The results revealed that the incorporation of Bi2S3 in the film increased the cavity density and uniformity, which provided additional space for the growth of active species and improved the interaction between dye pollutants and active sites. Zinc oxide acted as a mediator to facilitate the separation of electron-hole pairs effectively preventing their recombination, thus reducing the photo-corrosion of Bi2S3. As a result, the Bi2S3-ZnO/CA composite film exhibited favorable photocatalytic activity in the degradation of various dyes. Additionally, the composite film displayed effortless separation and recovery without the need for centrifugation or filtration, while maintaining its exceptional catalytic performance even after undergoing various processes.