Zn Single-Atom Catalysts Enable the Catalytic Transfer Hydrogenation of α,ß-Unsaturated Aldehydes.

Highly active nonprecious-metal single-atom catalysts (SACs) toward catalytic transfer hydrogenation (CTH) of α,ß-unsaturated aldehydes are of great significance but still are deficient. Herein, we report that Zn-N-C SACs containing Zn-N3 moieties can catalyze the conversion of cinnamaldehyde to cinnamyl alcohol with a conversion of 95.5% and selectivity of 95.4% under a mild temperature and atmospheric pressure, which is the first case of Zn-species-based heterogeneous catalysts for the CTH reaction. Isotopic labeling, in situ FT-IR spectroscopy, and DFT calculations indicate that reactants, coabsorbed at the Zn sites, proceed CTH via a "Meerwein-Ponndorf-Verley" mechanism. DFT calculations also reveal that the high activity over Zn-N3 moieties stems from the suitable adsorption energy and favorable reaction energy of the rate-determining step at the Zn active sites. Our findings demonstrate that Zn-N-C SACs hold extraordinary activity toward CTH reactions and thus provide a promising approach to explore the advanced SACs for high-value-added chemicals.

Kinetically Controlled Nucleation Enabled by Tunable Microfluidic Mixing for the Synthesis of Dendritic Au@Pt Core/Shell Nanomaterials.

The nucleation stage plays a decisive role in determining nanocrystal morphology and properties; hence, the ability to regulate nucleation is critical for achieving high-level control. Herein, glass microfluidic chips with S-shaped mixing units are designed for the synthesis of Au@Pt core/shell materials. The use of hydrodynamics to tune the nucleation kinetics is explored by varying the number of mixing units. Dendritic Au@Pt core/shell nanomaterials are controllably synthesized and a formation mechanism is proposed. As-synthesized Au@Pt exhibited excellent ethanol oxidation activity under alkaline conditions (8.4 times that of commercial Pt/C). This approach is also successfully applied to the synthesize of Au@Pd core/shell nanomaterials, thus demonstrating its generality.

Treatment of myelofibrosis with refractory anemia with luspatercept: a multicenter Chinese study.

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance.

Fe Single Atom Catalysts Promoting Polysulfide Redox Reduction in Quantum Dot Photovoltaics.

Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.

Single-Atom Gd Nanoprobes for Self-Confirmative MRI with Robust Stability.

Gadolinium (Gd)-based complexes are extensively utilized as contrast agents (CAs) in magnetic resonance imaging (MRI), yet, suffer from potential safety concerns and poor tumor targeting. Herein, as a mimic of Gd complex, single-atom Gd nanoprobes with r1 and r2 values of 34.2 and 80.1 mM-1 s-1 (far higher than that of commercial Gd CAs) at 3 T are constructed, which possessed T1 /T2 dual-mode MRI with excellent stability and good tumor targeting ability. Specifically, single-atom Gd is anchored on nitrogen-doped carbon matrix (Gd-Nx C) through spatial-confinement method, which is further subjected to controllable chemical etching to afford fully etched bowl-shape Gd-Nx C (feGd-Nx C) with hydrophilic properties and defined coordination structure, similar to commercial Gd complex. Such nanostructures not only maximized the Gd3+ site exposure, but also are suitable for self-confirmative diagnosis through one probe with dual-mode MRI. Moreover, the strong electron localization and interaction between Gd and N atoms afforded feGd-Nx C excellent kinetic inertness and thermal stability (no significant Gd3+ leaching is observed even incubated with Cu2+ and Zn2+ for two months), providing a creative design protocol for MRI CAs.

Ethical Challenges of Virtual Reality Technology Interventions for the Vulnerabilities of Patients With Chronic Pain: Exploration of Technician Responsibility.

Chronic pain, a common disease, is a crucial global public health concern. Approximately 20% of the worldwide population is affected by chronic pain, which accounts for 15% to 20% of hospital visits. In Canada, approximately 7.6 million people-or 1 in 5 people-experience chronic pain. Among this population, 60% has either lost their employment or experienced a reduction in income as a result of their pain. The proportion of older people (aged ≥65 years) with chronic pain is high, comprising one-third of the total older population. In addition, the causes of chronic pain and its cures are unknown, and treatment is limited by these unknowns and the dangers of opioids. These essential factors make patients with chronic pain one of the most vulnerable populations. The use of emerging virtual reality (VR) technology as an intervention for chronic pain has consistently demonstrated early effectiveness and has been termed as a "nonpharmacological analgesic." Nevertheless, we must remain vigilant about the potential ethical risks of VR interventions, as inappropriate VR interventions may exacerbate the vulnerabilities of patients. Currently, a central challenge for VR developers is the ambiguity of patient vulnerability and the unpredictability of ethical dilemmas. Therefore, our paper focused on the vulnerability and ethical dilemmas faced by patients with chronic pain in VR interventions. Through an experience-based, prospective ethical examination, we have identified both existing and potential new vulnerabilities and specific manifestations that patients with chronic pain may encounter in VR interventions. Our aim was to highlight the ethical risks that may be present in VR interventions. On one hand, this can help raise awareness among technology developers regarding the vulnerabilities of patients with chronic pain and mitigate technological ethical risks. In addition, it can assist technology developers in determining the priorities for VR technology interventions. These efforts collectively lay a solid foundation for the comprehensive realization of responsible VR technology interventions.

L-Theanine and Immunity: A Review.

L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with its sedative and calming activities, the immunomodulatory effects of L-theanine have received less attention. Clinical and epidemiological studies have shown that L-theanine reduces immunosuppression caused by strenuous exercise and prevents colds and influenza by improving immunity. Numerous cell and animal studies have proven that theanine plays an immunoregulatory role in inflammation, nerve damage, the intestinal tract, and tumors by regulating γδT lymphocyte function, glutathione (GSH) synthesis, and the secretion of cytokines and neurotransmitters. In addition, theanine can be used as an immunomodulator in animal production. This article reviews the research progress of L-theanine on immunoregulation and related mechanisms, as well as its application in poultry and animal husbandry. It is hoped that this work will be beneficial to future related research.

Acid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo-Chemodynamic Therapy.

The real-time tracking and efficacy evaluation of therapeutic nanoplatforms especially in deep-tissues is of great importance but faces challenges. Meanwhile, chemodynamic therapy (CDT), relying on Fenton reaction by converting H2O2 into toxic hydroxyl radicals (•OH), has drawn wide interests in the fabrication of nanozymes for tumor therapy, while endogenous H2O2 is usually insufficient for effective CDT. Here, we report the pH-responsive multifunctional nanoplatforms consisting of copper peroxide (CP) nanoparticles, paclitaxel (PTX) and perfluoro-15-crown-5-ether (PFCE), for 19F magnetic resonance imaging guided and enhanced chemo-chemodynamic synergetic therapy with self-supplied H2O2 stemmed from the decomposition of CP nanoparticles under acid conditions in tumor. The decomposition of CP nanoparticles further promotes the release of PTX for enhanced chemotherapy. Both in vitro and in vivo results indicate that the efficient generation of •OH and drug release effectively inhibits tumor growth. Furthermore, 19F MRI signal can clearly track the fate of nanoplatforms in tumor and guide tumor treatment. This work provides a promising strategy for the rational design and construction of multifunctional nanoplatforms for imaging-guided synergistic therapy of deep seated tumor.

In Situ Fabrication of Nanoprobes for 19F Magnetic Resonance and Photoacoustic Imaging-Guided Tumor Therapy.

It is challenging to fabricate multimodal imaging nanoprobes with high penetration depth and long blood circulation. Herein, we present multifunctional fluorinated nanoprobes (CFPP NPs) containing in situ formed copper chalcogenide nanoparticles for 19F magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). The formed hydrophilic copper chalcogenide nanoassemblies demonstrated easy excretion stemming from facile disassembly, enhanced photothermal ability, and novel localized surface plasmon resonance (LSPR) absorption (centered at 1064 nm) in the "biological transparent" region. Both 19F MRI and PAI render these CFPP NPs suitable for multimodal imaging with high penetration depth and low background. Moreover, the chemo-photothermal synergistic therapy results suggest great potential in multimodal nanoprobes for imaging-guided tumor therapy applications.

Dual-Channel Recognition of Human Serum Albumin and Glutathione by Fluorescent Probes with Site-Dependent Responsive Features.

Design of chemical probes with high specificity and responses are particularly intriguing. In this work, a fluorescent probe (M-OH-SO3) with dual-channel spectral responses toward human serum albumin (HSA) is presented. By employing dinitrobenzenesulfonate as a recognition site as well as a fluorescence quencher, probe M-OH-SO3 displayed weak fluorescence, which, nevertheless, exhibits extensive yellow (575 nm) and red (660 nm) fluorescence emissions toward HSA under excitations at 400 and 500 nm, respectively. Interestingly, M-OH-SO3 displayed the best performance toward HSA with distinctly higher selectivity than that of its counterparts M-SO3, M-H-SO3, and M-F-SO3, which were prepared simply by modulating the functional group at the ortho position of the dicyanoisophorone core. Molecular docking results revealed that M-OH-SO3 possesses the lowest binding energy among the tested derivatives and accordingly the strongest binding affinity. Probe M-OH-SO3 showed a good linear relationship toward HSA in a range of 0.5-18 µM with a limit of detection of 35 nM. Cell imaging results demonstrated that probe M-OH-SO3 could visualize the variation HSA levels in hepatocarcinoma cells. In addition, probe M-OH-SO3 could also be employed for the recognition of glutathione through the cleavage of the dinitrobenzenesulfonate group along with an enhancement of emission at 575 nm. The site-dependent properties inspired a novel paradigm for design of fluorescent probes with optimized selectivity and responses.

Stepwise-Enhanced Tumor Targeting of Near-Infrared Emissive Au Nanoclusters with High Quantum Yields and Long-Term Stability.

We developed an in situ coordination-driven spatially confined strategy for preparing near-infrared emissive gold nanoclusters encapsulated by fluorinated polymers (AuNCs@PF, λmax = 810 nm) with good stability and high quantum yields (27.7%), far higher than those previously reported for NIR AuNCs (>800 nm). Based on the stepwise enhancements including long blood circulation-induced passive tumor targeting, fluoro-enhanced tumor permeation, and tumor microenvironment (weak acid)-induced aggregation retention in cells, these AuNCs demonstrated bright and stable NIR fluorescence imaging ability in tumors. Additionally, the AuNCs@PF were capable of fluorine magnetic resonance imaging and computed tomographic imaging. The multimodal imaging of tumor-bearing mice clearly implied the potential of AuNCs@PF in biomedical fields.

Coordination-Driven Self-Assembly of Iron Oxide Nanoparticles for Tumor Microenvironment-Responsive Magnetic Resonance Imaging.

Accurate diagnosis of diseases located in deep tissues is always challenging. The "always-on" probe often leads to false-positive signals due to nonspecific interaction of nanoprobes. Thus, stimuli-responsive nanoprobes are highly desirable, which, however, require complicated surface modification so as to achieve trigger-induced signal changes. Here pH-triggered switchable magnetic resonance imaging (MRI) nanoprobes were constructed by coordination-driven self-assembly of monodispersed iron oxide nanoparticles (MIONPs) with simple amino acid derivatives, which displayed typical T2-weighted MRI features, yet, were turned into T1-weighted MRI under slightly acidic conditions at the tumor site. The dynamic assembly and disassembly properties of MIONPs afford T2/T1 switchable contrast imaging, enabling selective "turn-on" signals at the tumor site with high specificity.

NIR Responsive Injectable Nanocomposite Thermogel System Against Osteosarcoma Recurrence.

Compared to traditional postoperative radiation and chemotherapy, immune checkpoint blockade (ICB) therapy demonstrates superiority by provoking own immune system to cure cancer completely even for some terminally ill patients. However, systemic administration of ICB is liable to cause severe immunity inflammation or immune storm. Here, an injectable, near infrared (NIR) responsive, multifunctional nanocomposite thermogel as a local ICB delivery system for cancer postsurgical therapy is proposed. By copolymerization of thermosensitive and zwitterionic monomer, the injectable thermogel with adjustable sol-gel transition temperature is obtained. Afterward, combined with functional mesoporous nanoparticles, the platform can absorb NIR light and transfer it into heat. The generated heat will promote retro Diels-Alder (D-A) reaction to degrade coating layer on nanoparticle, achieving NIR controlled ICB release. Furthermore, the local ICB delivery system is applied on an osteosarcoma postsurgical recurrence model and results indicate the platform with favorable biocompatibility can avoid early leakage of cargos and greatly increase drug content at tumor site. Besides, long-term controlled ICB release of the system effectively improves the amount of active T cells, resulting in excellent antitumor recurrence effect. Overall, this work suggests the local injectable nanocomposite thermogel is expected to be a promising tool for cancer postoperative therapy.

19F-Grafted Fluorescent Carbonized Polymer Dots for Dual-Mode Imaging.

Dual-modal imaging systems could provide complementary information by taking advantage of each imaging modality. Herein, a fluorescence and 19F magnetic resonance imaging nanoprobe was developed through preparation of 19F-grafted fluorescent carbonized polymer dots (FCPDs). Both fluorescence and 19F nuclear magnetic resonance intensities of these FCPDs can be modulated by controlling the carbonization processes. The strong yellow fluorescence renders these FCPDs capable of cell fluorescence imaging. The in vitro and in vivo assessments demonstrated that the as-prepared FCPDs were suitable for 19F magnetic resonance imaging (19F MRI), which would provide great potential for biological imaging and early diagnosis applications. Moreover, this fabrication strategy offers a new protocol for 19F MRI nanoprobe design.

Selective Ligand Sensitization of Lanthanide Nanoparticles for Multilevel Information Encryption with Excellent Durability.

Durable and multilevel information encryption technology has been of great importance in recent decades. Here, an inkjet printer-adaptable invisible ink was prepared with lanthanide nanoparticles, and optical decoding of information could only be achieved when specific ligand dipicolinic acid was utilized in the presence of UV illumination. In addition, the proposed protocols displayed long shelf life (>one year) and excellent durability even at harsh conditions such as in the presence of strong acids (1 M HCl) and alkalis (1 M NaOH). Meanwhile, such invisible inks could be further employed on a soft matrix via screen-printing, holding great potential for practical applications.

Research advances in hydrogen-deuterium exchange mass spectrometry for protein epitope mapping.

With the development of biomedical technology, epitope mapping of proteins has become critical for developing and evaluating new protein drugs. The application of hydrogen-deuterium exchange for protein epitope mapping holds great potential. Although several reviews addressed the hydrogen-deuterium exchange, to date, only a few systematic reviews have focused on epitope mapping using this technology. Here, we introduce the basic principles, development history, and review research progress in hydrogen-deuterium exchange epitope mapping technology and discuss its advantages. We summarize the main hurdles in applying hydrogen-deuterium exchange epitope mapping technology, combined with relevant examples to provide specific solutions. We describe the epitope mapping of virus assemblies, disease-associated proteins, and polyclonal antibodies as examples of pattern introduction. Finally, we discuss the outlook of hydrogen-deuterium exchange epitope mapping technology. This review will help researchers studying protein epitopes to gain a more comprehensive understanding of this technology.

Multiresponsive Nanoprobes for Turn-On Fluorescence/19F MRI Dual-Modal Imaging.

Multiresponsive nanoprobes are highly desirable for low background and highly sensitive imaging in biomedical applications. Herein, we design a glutathione (GSH)/pH dual-responsive nanoprobe capable of both fluorescence imaging in cells and 19F magnetic resonance imaging (19F MRI) in deep tissue, by encapsulating manganese oleate (Mn(OA)2) on the surface of fluorinated fluorescent quantum dots (F-ZnS:Mn2+). In this approach, Mn(OA)2 serves as an efficient quencher of both fluorescence and 19F MRI signal. Both the fluorescence and 19F MRI signal can be turned on by introducing glutathione (GSH) that breaks up the Mn-O bonds within Mn(OA)2 under weak acidity conditions (e.g., pH 6.0). The imaging results in cells and mice suggest that this novel strategy can offer a promising nanoprobe for turn-on fluorescence/19F MRI dual-modal tumor imaging.

Intratumoral Glutathione Activatable Nanoprobes for Fluorescence and 19F Magnetic Resonance Turn-On Imaging.

Tumor microenvironment turn-on nanoprobes that could specifically detect the occurrence of diseases possess great potential in early diagnosis. Here, a GSH activated nanoprobe was designed for fluorescence and 19F magnetic resonance (MR) dual-modal turn-on imaging of tumors. Specifically, fluorescence AgInS2 quantum dots (QDs for fluorescence imaging) were co-encapsulated with perfluoro-15-crown-5-ether (P19FCE for19F MRI) by amphiphilic polymers and further coated with in situ formed manganese dioxide (MnO2) nanoshells, which served as efficient fluorescence and 19F MR quenchers due to energy transfer and paramagnetic relaxation effects, respectively. The over-expressed GSH in tumors would decompose the MnO2 nanoshells, resulting in remarkable enhancement of both fluorescence and 19F MRI signals of the nanoprobes, accordingly lighting up the tumor site.

Ethanol Extract of Campsis grandiflora Flower and Its Organic Acid Components Have Inhibitory Effects on Autoinducer Type 1 Quorum Sensing.

Chinese herbs are a useful resource bank for natural drug development, and have attracted considerable attention to exploit quorum sensing inhibitors (QSIs). This study was designed to screen QSIs from raw Chinese herb materials. Of the 38 common herbs examined, the ethanol extract of Campsis grandiflora flower had the strongest QSI activity. The C. grandiflora flower ethanol extract (CFEE) was purified by HPD600, and the QSI activities were examined in further detail. CFEE inhibited violacein production of Chromobacterium violaceum 026 in a dose-dependent manner, and inhibit the swarming abilities of Escherichia coli K-12 and Pseudomonas aeruginosa PAO1. Furthermore, CFEE could inhibited biofilm formation and destroyed mature biofilms of E. coli K-12 and P. aeruginosa PAO1. The composition of CFEE was determined by UPLC-MS/MS to distinguish active QSI compounds, and 21 compounds were identified. In addition to gallic acid and caffeic acid, two organic acids, malic acid and succinic acid, were confirmed for the first time to have autoinducer type 1 QSI activities. Therefore, CFEE is a potential QSI that could be used as a novel antimicrobial agent and should be considered for medicinal development.

Quantitative ligand and receptor binding studies reveal the mechanism of interleukin-36 (IL-36) pathway activation.

IL-36 cytokines signal through the IL-36 receptor (IL-36R) and a shared subunit, IL-1RAcP (IL-1 receptor accessory protein). The activation mechanism for the IL-36 pathway is proposed to be similar to that of IL-1 in that an IL-36R agonist (IL-36α, IL-36ß, or IL-36γ) forms a binary complex with IL-36R, which then recruits IL-1RAcP. Recent studies have shown that IL-36R interacts with IL-1RAcP even in the absence of an agonist. To elucidate the IL-36 activation mechanism, we considered all possible binding events for IL-36 ligands/receptors and examined these events in direct binding assays. Our results indicated that the agonists bind the IL-36R extracellular domain with micromolar affinity but do not detectably bind IL-1RAcP. Using surface plasmon resonance (SPR), we found that IL-1RAcP also does not bind IL-36R when no agonist is present. In the presence of IL-36α, however, IL-1RAcP bound IL-36R strongly. These results suggested that the main pathway to the IL-36R·IL-36α·IL-1RAcP ternary complex is through the IL-36R·IL-36α binary complex, which recruits IL-1RAcP. We could not measure the binding affinity of IL-36R to IL-1RAcP directly, so we engineered a fragment crystallizable-linked construct to induce IL-36R·IL-1RAcP heterodimerization and predicted the binding affinity during a complete thermodynamic cycle to be 74 µm The SPR analysis also indicated that the IL-36R antagonist IL-36Ra binds IL-36R with higher affinity and a much slower off rate than the IL-36R agonists, shedding light on IL-36 pathway inhibition. Our results reveal the landscape of IL-36 ligand and receptor interactions, improving our understanding of IL-36 pathway activation and inhibition.