Spatially Confined Microcells: A Path toward TMD Catalyst Design.

With the ability to maximize the exposure of nearly all active sites to reactions, two-dimensional transition metal dichalcogenide (TMD) has become a fascinating new class of materials for electrocatalysis. Recently, electrochemical microcells have been developed, and their unique spatial-confined capability enables understanding of catalytic behaviors at a single material level, significantly promoting this field. This Review provides an overview of the recent progress in microcell-based TMD electrocatalyst studies. We first introduced the structural characteristics of TMD materials and discussed their site engineering strategies for electrocatalysis. Later, we comprehensively described two distinct types of microcells: the window-confined on-chip electrochemical microcell (OCEM) and the droplet-confined scanning electrochemical cell microscopy (SECCM). Their setups, working principles, and instrumentation were elucidated in detail, respectively. Furthermore, we summarized recent advances of OCEM and SECCM obtained in TMD catalysts, such as active site identification and imaging, site monitoring, modulation of charge injection and transport, and electrostatic field gating. Finally, we discussed the current challenges and provided personal perspectives on electrochemical microcell research.

Hedgehog signaling is required for larval muscle development and larval metamorphosis of the mussel Mytilus coruscus.

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.

In Situ Tracking of Water Oxidation Generated Nanoscale Dynamics in Layered Double Hydroxides Nanosheets.

Layered double hydroxides (LDHs) are potential catalysts for water oxidation, and it is recognized that they undergo dynamic evolution during the operation. However, little is known about the interfacial behaviors at the nanoscale under working conditions nor the underlying effects on electrocatalytic performance. Herein, using electrochemical atomic force microscopy, we in situ visualize the heterogeneous evolution of LDH nanosheets during oxygen evolution reaction (OER). By further combining density functional theory calculations, we elucidate the origin of the heterogeneous dynamics and their impact on the OER efficiency. Our findings demonstrate that NiCo LDHs transform to the catalytically active NiCoOx(OH)2-x phase during OER, and the redox transition between is accompanied by compressive and tensile strain, leading to in-plane contraction and reversible expansion of the nanosheets. Nonisotropic strain and out-of-plane strain relaxation due to defects and interparticle interactions result in cracking and wrinkling in the nanostructure, which is responsible for the partial activation and long-term deterioration of LDH electrocatalysts toward the OER. With this knowledge, we suggest and validate that engineering defects can precisely tune these dynamic behaviors, improving the OER activity and stability among LDH-based electrocatalysts.

Electrocatalysis Boosts the Methanol Thermocatalytic Dehydrogenation for High-Purity H2 and CO Production.

Hydrogen production from methanol represents an energy-sustainable way to produce ethanol, but it normally results in heavy CO2 emissions. The selective conversion of methanol into H2 and valuable chemical feedstocks offers a promising strategy; however, it is limited by the harsh operating conditions and low conversion efficiency. Herein, we realize efficient high-purity H2 and CO production from methanol by coupling the thermocatalytic methanol dehydrogenation with electrocatalytic hydrogen oxidation on a bifunctional Ru/C catalyst. Electrocatalysis enables the acceleration of C-H cleavage and reduces the partial pressure of hydrogen at the anode, which drives the chemical equilibrium and significantly enhances methanol dehydrogenation. Furthermore, a bilayer Ru/C + Pd/C electrode is designed to mitigate CO poisoning and facilitate hydrogen oxidation. As a result, a high yield of H2 (558.54 mmol h-1 g-1) with high purity (99.9%) was achieved by integrating an applied cell voltage of 0.4 V at 200 °C, superior to the conventional thermal and electrocatalytic processes, and CO is the main product at the anode. This work presents a new avenue for efficient H2 production together with valuable chemical synthesis from methanol.

Hypersensitive MR Angiography for Diagnosis of Ischemic Stroke and Reperfusion Subarachnoid Hemorrhage.

Stroke is an acute injury of the central nervous system caused by the disorders of cerebral blood circulation, which has become one of the major causes of disability and death. Hemorrhage, particularly subarachnoid hemorrhage (SAH), is one of the poorest prognostic factors in stroke, which is related to the thrombolytic therapy, and has been considered very dangerous. In this context, the MR angiography with high sensitivity and resolution has been developed based on biocompatible paramagnetic ultrasmall NaGdF4 nanoprobes. Owing to the appropriate hydrodynamic diameter, the nanoprobe can be confined inside the blood vessels and it only extravasates at the vascular injury site when the bleeding occurs. Relying on this property, the three-dimensional (3D) anatomic structures of artery occlusion of stroke rat can be precisely visualized; reperfusion-related SAH has been successfully visualized and identified. Benefiting from the long blood half-life of the nanoprobe, the observation window of MR angiography can last for the whole period of reperfusion, thereby monitoring the probable SAH in real time during thrombolytic therapy. More importantly, through reconstruction of multiparametric MRI, the arterial occlusion, cerebral ischemic region, and SAH can be simultaneously visualized in vivo in a 3D manner for the first time. Therefore, the current study provides a novel approach for both noninvasive 3D vascular visualization and hemorrhage alert, which possesses great prospects for clinical translation.

LPG 18:0 is a general biomarker of asthma and inhibits the differentiation and function of regulatory T cells.

BACKGROUND: The diagnosis, severity assessment, and development of therapeutic strategies for asthma are crucial aspects of disease management. Since biomarkers are reliable tools in disease management, we aimed to identify and explore asthma-associated biomarkers and investigate their mechanisms. METHODS: Lipidomics was used to profile serum glycerophospholipids in asthmatic patients and controls. The absolute concentration of lysophosphatidylglycerol (LPG) 18:0 was quantified in various asthma subtypes. Mouse asthma models were used to confirm its potential as a biomarker and investigate its mechanisms in vivo. The effects of LPG 18:0 on CD4+ T cell differentiation, proliferation, and apoptosis were assessed in vitro by flow cytometry, while mitochondrial dysfunction was evaluated through mitochondrial membrane potential, reactive oxygen species, and ATP production measurements. The intracellular mechanism of LPG 18:0 in Tregs was investigated using small molecule inhibitors. RESULTS: The serum glycerophospholipid profile varied between asthmatic patients and control group, with LPG 18:0 levels being notably higher in asthmatic patients, correlating with asthma severity and control level. In vivo and in vitro studies revealed that LPG18:0 impaired naïve CD4+ T cell differentiation into Tregs and compromised their suppressive function. Further investigation demonstrated that LPG18:0 treatment reduced the FOXP3 protein level via SIRT1-mediated deacetylation during Treg differentiation. CONCLUSIONS: This study identifies that serum levels of LPG 18:0 are generally elevated in asthmatics and serve as a biomarker for asthma. LPG 18:0 impairs Treg function via the NAD+/SIRT1/FOXP3 pathway. Our research reveals the potential of LPG18:0 as a biomarker for asthma, elucidating its role in asthma diagnosis and treatment.

Strategies Toward High Selectivity, Activity, and Stability of Single-Atom Catalysts.

Single-atom catalysts (SACs) hold immense promise in facilitating the rational use of metal resources and achieving atomic economy due to their exceptional atom-utilization efficiency and distinct characteristics. Despite the growing interest in SACs, only limited reviews have holistically summarized their advancements centering on performance metrics. In this review, first, a thorough overview on the research progress in SACs is presented from a performance perspective and the strategies, advancements, and intriguing approaches employed to enhance the critical attributes in SACs are discussed. Subsequently, a comprehensive summary and critical analysis of the electrochemical applications of SACs are provided, with a particular focus on their efficacy in the oxygen reduction reaction , oxygen evolution reaction, hydrogen evolution reaction , CO2 reduction reaction, and N2 reduction reaction . Finally, the outline future research directions on SACs by concentrating on performance-driven investigation, where potential areas for improvement are identified and promising avenues for further study are highlighted, addressing challenges to unlock the full potential of SACs as high-performance catalysts.

Study on dynamic response characteristics of the scanning angle in a liquid crystal cladding waveguide beam scanner.

This paper studies the dynamic response characteristics of the scanning angle in a liquid crystal cladding waveguide beam scanner. Based on liquid crystal dynamic theory, finite element analysis and vectorial refraction law, a dynamic response calculation model of scanning angle is constructed. The simulation results show that the dynamic responses of the scanning angle during the electric field-on and field-off processes are asymmetric, and exhibit "S"-shape and "L"-shape changing trends, respectively. In addition, by comparing with the bulk phase modulation response process of traditional liquid crystal devices, the intrinsic physical reason for the rapid light regulation of the liquid crystal cladding waveguide beam scanner is clarified to be that the liquid crystal close to the core layer has a faster rotation speed during the electric field-off process. Moreover, the liquid crystal cladding waveguide beam scanner is experimentally tested, and the experiment results are in good agreement with theoretical simulations.

Oxidative [4+2] Annulation of Pyrrole-2-carbaldehyde Derivatives with o-Hydroxyphenyl Propargylamines: Syntheses of 5,6,7-Trisubstituted Indolizines.

A base promoted oxidative [4+2] annulation of pyrrole-2-carbaldehyde derivatives with o-hydroxyphenyl propargylamines for the synthesis of highly substituted indolizines has been developed. Using DBN as base, a broad range of 5,6,7-trisubstituted indolizines have been prepared in good to excellent yields under mild conditions, and many useful functional groups can be tolerated.

Modification Strategies of Hexagonal Boron Nitride Nanomaterials for Photocatalysis.

Although hexagonal boron nitride (h-BN) was initially considered a less promising photocatalyst due to its large band gap and apparent chemical inertness, its unique two-dimensional lamellar structure coupled with high stability and environmental friendliness, as the second largest van der Waals material after graphene, provides a unique platform for photocatalytic innovation. This review not only highlights the intrinsic qualities of h-BN with photocatalytic potentials, such as high stability, environmental compatibility, and tunable bandgap through various modification strategies but also provides a comprehensive overview of the recent advances in h-BN-based nanomaterials for environmental and energy applications, as well as an in-depth description of the modification methods and fundamental properties for these applications. In addition, we discuss the challenges and prospects of h-BN-based nanomaterials for future photocatalysis.

Cooperative Cu/Pd-Catalyzed 1,5-Boroacylation of Cyclopropyl-Substituted Alkylidenecyclopropanes.

A Cu/Pd-cocatalyzed 1,5-boroacylation of cyclopropyl-substituted ACPs with B2pin2 and acid chlorides has been developed. Using cyclopropyl-substituted ACPs as the starting material, a broad range of 1,5-boroacylated products with multiple functional groups was prepared in good yields with excellent regio- and stereoselectively. Both aromatic and aliphatic acid chlorides were tolerated in this reaction.

Characterization of the G-quadruplexes in the transthyretin gene and its role in silencing transthyretin mRNA transcription.

Transthyretin Amyloidosis arises from the misfolding of monomers or oligomers of the normal transthyretin protein. Our investigation revealed that certain guanine-rich regions within the 5' UTR sequence of the transthyretin gene possess the ability to form G2-quadruplex structures, as determined through analysis with QGRS mapper. We demonstrated that small molecule ligands, including TMPyP4, Braco-19, NMM, and TO, have a significant impact on the stabilization of transthyretin G-quadruplexes. The objective of this study was to confirm the effect of ligands on transthyretin gene transcription through the stabilization of G-quadruplexes. To comprehend the interaction between ligands and transthyretin G-quadruplexes, a range of analytical techniques were employed, includingUV titration, fluorescence titration assays, circular dichroism, quantitative RT-PCR and cytotoxicity tests. The results revealed the presence of four putative G2-quadruplex sequences, which formed stable anti-parallel, parallel, and hybrid G2-quadruplex structures. Notably, Ttrg 3 (5'-GGAAGGAAGGGAGGGAGGG-3') exhibited the highest stability to form G-quadruplex. Furthermore, TmPyP4, Braco-19, NMM and TO were found to stabilize the parallel topology of Ttrg 3. After 48 h of incubation, the RT-PCR experiments revealed a significant reduction in transthyretin mRNA transcription in HepG2 cells when treated with 20 µM TmPyP4 and Braco-19, without inducing apoptosis. Our findings suggested that ligand-mediated stabilization of G-quadruplexes within the 5'-UTR can effectively silence transthyretin expression, highlighting the potential of G-quadruplex as a novel therapeutic target for Transthyretin Amyloidosis. This study might shed valuable lights for the development of innovative therapeutic approach against Transthyretin Amyloidosis.

A visible-light-catalyzed sulfonylation reaction of an aryl selenonium salt via an electron donor-acceptor complex.

An efficient synthesis of sulfone structures through selenonium salts and sodium sulfinates was developed. Under the irradiation of a blue LED lamp, the two substrates generate aryl and sulfonyl radicals through the activation of the intermediate electron donor acceptor (EDA) complex, thereby synthesizing aromatic, heteroaromatic and aliphatic sulfones in medium to good yields. The advantages of this strategy are metal-free, mild conditions and the leaving group is recycled to construct new selenonium salts.

Regulating the Chiroptical Expression of Aggregated Solvophobic Core by Solvophilic Segments.

The investigation of chiral supramolecular stacking is of essential significance for the understanding of the origin of homochirality in nature. Unlike structurally well-defined amphiphilic liposomes, it remains unclear whether the solvophilic segments of the amphiphilic block copolymer play a decisive role in the construction of asymmetric superstructures. Herein, insights are presented into the stacking patterns and morphological regulation in azobenzene-containing block copolymer assemblies solely by modulating the solvophilic chain length. The solvophilic poly(methacrylic acid) (PMAA) segments of different molecular weights could cause multi-mode chirality inversions involving stacking transitions between intra-chain π-π stacking, inter-chain H- and J-aggregation. Furthermore, the length of the solvophilic PMAA also affects the morphology of the chiral supramolecular assemblies; rice grain-like micelles, worms, nanofibers, floccules, and lamellae can be prepared at different solvophilic-solvophobic balance. The comprehensive mechanism is collectively revealed by utilizing various measurement methods, such as including circular dichroism (CD), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD). This study highlights the critical importance of fully dissolved solvophilic segments for the chiroptical regulation of the aggregated core, providing new insights into the arrangement of chiral supramolecular structures in polymer systems.

Nanopore sequencing for smear-negative pulmonary tuberculosis-a multicentre prospective study in China.

PURPOSE: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. METHODS: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. RESULTS: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss' kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden's index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods. CONCLUSIONS: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF's nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.

Environmental antibiotics exposure and childhood obesity: A cross-sectional case-control study.

Children's exposures to environmental antibiotics are a major public health concern. However, limited data are available on the effects of environmental antibiotic exposures on childhood obesity. Our study aimed to explore this relationship. We conducted a cross-sectional case-control study nested in a population-based survey of primary school students, including 1855 obese and 1875 random selected control children. A total of 10 antibiotics in urine samples were measured by liquid chromatography-tandem mass spectrometry. Multivariable survey logistic regression was used to assess the associations between environmental antibiotics exposures and childhood obesity. After adjusting for potential confounders, increased odds of obesity were observed in children exposed to tetracycline (OR = 1.31, 95% CI: 1.09-1.57) and sulfamonomethoxine (OR = 1.43, 95% CI: 1-2.05). Comparing none (

Polyphyllin II inhibits NLPR3 inflammasome activation and inflammatory response of Mycobacterium tuberculosis-infected human bronchial epithelial cells.

BACKGROUND: The bronchial infection by Mycobacterium tuberculosis (Mtb) is increasing in prevalence and severity worldwide. Despite appropriate tuberculosis treatment, most patients still develop bronchial stenosis, which often leads to disability. Polyphyllin II (PP2) is a steroidal saponin extracted from Rhizoma Paridis. In this study, we aimed to explore the effect of PP2 on the advancement of Mtb-induced bronchial infection. METHOD: The effects of PP2 on cell viability were measured by using MTT and lactate dehydrogenase (LDH) kit. The mRNA and protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-8 were elucidated by RT-qPCR and ELISA, respectively. The expression of NLR family pyrin domain containing 3 (NLRP3) related inflammasome (NLRP3, IL-1ß, and cleaved-caspase-1) and the activated degree of protein kinase B (AKT)/nuclear factor-kappa B (NF-kB; p-AKT and p-NF-κB) were detected by Western blotting. RESULTS: PP2 at 0, 1, 5, and 10 µM had little cytotoxicity on 16HBE cells. PP2 inhibited Mtb-induced cell proliferation and decreased LDH levels. We further found that PP2 could suppress Mtb-induced inflammatory responses and activation of NLPR3 inflammasome. Additionally, the role of PP2 in Mtb is associated with the AKT/NF-kB signaling pathway. CONCLUSION: PP2 inhibited Mtb infection in bronchial epithelial cells, by inhibiting Mtb-induced inflammatory reactions and activation of NLPR3 inflammasome. These effects may be exerted by suppressing the AKT/NF-kB pathway, which will provide a prospective treatment.

Oleandrin enhances radiotherapy sensitivity in lung cancer by inhibiting the ATM/ATR-mediated DNA damage response.

Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.

Deep learning automatically assesses 2-µm laser-induced skin damage OCT images.

The present study proposed a noninvasive, automated, in vivo assessment method based on optical coherence tomography (OCT) and deep learning techniques to qualitatively and quantitatively analyze the biological effects of 2-µm laser-induced skin damage at different irradiation doses. Different doses of 2-µm laser irradiation established a mouse skin damage model, after which the skin-damaged tissues were imaged non-invasively in vivo using OCT. The acquired images were preprocessed to construct the dataset required for deep learning. The deep learning models used were U-Net, DeepLabV3+, PSP-Net, and HR-Net, and the trained models were used to segment the damage images and further quantify the damage volume of mouse skin under different irradiation doses. The comparison of the qualitative and quantitative results of the four network models showed that HR-Net had the best performance, the highest agreement between the segmentation results and real values, and the smallest error in the quantitative assessment of the damage volume. Based on HR-Net to segment the damage image and quantify the damage volume, the irradiation doses 5.41, 9.55, 13.05, 20.85, 32.71, 52.92, 76.71, and 97.24 J/cm² corresponded to a damage volume of 4.58, 12.56, 16.74, 20.88, 24.52, 30.75, 34.13, and 37.32 mm³. The damage volume increased in a radiation dose-dependent manner.

Lipid droplets-specific fluorescent probe for wash-free imaging and in vivo diagnosis of non-alcoholic fatty liver disease.

Lipid droplets (LDs) dysfunction is closely associated with a multitude of diseases, including nonalcoholic fatty liver disease (NAFLD). Therefore, it is imperative to develop fluorescent probes that specifically target LDs for the early detection and diagnosis of NAFLD. In this study, a series of lipophilic fluorophores CZ1-CZ4 that feature a D-π-A configuration were designed and synthesized based on the carbazole and tricocyanofuran derivatives. The photophysical data revealed that all four probes exhibited large Stokes shifts (~ 120 nm) in high-polarity solvents (e.g., DMSO) and demonstrated enhanced fluorescence in solvents ranging from low-polarity (e.g., 1,4-Dioxane) to high-polarity. Notably, by utilizing probe CZ1, we could specifically visualize LDs and captured high-quality images, even eliminating the need for a time-consuming wash procedure. Moreover, CZ1 enabled monitoring of LDs dynamic changes in-real time within live cells, and importantly, it could be used to effectively distinguish normal and NAFLD tissues at both the organ and in vivo level. This exceptional property of probe CZ1 provides a practical tool for the diagnosis and intervention of NAFLD.