Automated optimization of the solubility of a hyper-stable α-amylase.

Most successes in computational protein engineering to date have focused on enhancing one biophysical trait, while multi-trait optimization remains a challenge. Different biophysical properties are often conflicting, as mutations that improve one tend to worsen the others. In this study, we explored the potential of an automated computational design strategy, called CamSol Combination, to optimize solubility and stability of enzymes without affecting their activity. Specifically, we focus on Bacillus licheniformis α-amylase (BLA), a hyper-stable enzyme that finds diverse application in industry and biotechnology. We validate the computational predictions by producing 10 BLA variants, including the wild-type (WT) and three designed models harbouring between 6 and 8 mutations each. Our results show that all three models have substantially improved relative solubility over the WT, unaffected catalytic rate and retained hyper-stability, supporting the algorithm's capacity to optimize enzymes. High stability and solubility embody enzymes with superior resilience to chemical and physical stresses, enhance manufacturability and allow for high-concentration formulations characterized by extended shelf lives. This ability to readily optimize solubility and stability of enzymes will enable the rapid and reliable generation of highly robust and versatile reagents, poised to contribute to advancements in diverse scientific and industrial domains.

Distinct eLPBChAT projections for methamphetamine withdrawal anxiety and primed reinstatement of conditioned place preference.

Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains unclear. Our recent research has identified a specific subpopulation of choline acetyltransferase (ChAT+) neurons localized in the external lateral portion of parabrachial nucleus (eLPBChAT), which modulates METH primed-reinstatement of conditioned place preference (CPP). Here, the anatomical structures and functional roles of eLPBChAT projections in METH withdrawal anxiety and primed reinstatement were further explored. Methods: In the present study, a multifaceted approach was employed to dissect the LPBChAT+ projections in male mice, including anterograde and retrograde tracing, acetylcholine (Ach) indicator combined with fiber photometry recording, photogenetic and chemogenetic regulation, as well as electrophysiological recording. METH withdrawal anxiety-like behaviors and METH-primed reinstatement of conditioned place preference (CPP) were assessed in male mice. Results: We identified that eLPBChAT send projections to PKCδ-positive (PKCδ+) neurons in lateral portion of central nucleus of amygdala (lCeAPKCδ) and oval portion of bed nucleus of the stria terminalis (ovBNSTPKCδ), forming eLPBChAT-lCeAPKCδ and eLPBChAT-ovBNSTPKCδ pathways. At least in part, the eLPBChAT neurons positively innervate lCeAPKCδ neurons and ovBNSTPKCδ neurons through regulating synaptic elements of presynaptic Ach release and postsynaptic nicotinic acetylcholine receptors (nAChRs). METH withdrawal anxiety and METH-primed reinstatement of CPP respectively recruit eLPBChAT-lCeAPKCδ pathway and eLPBChAT-ovBNSTPKCδ pathway in male mice. Conclusion: Our findings put new insights into the complex neural networks, especially focusing on the eLPBChAT projections. The eLPBChAT is a critical node in the neural networks governing METH withdrawal anxiety and primed-reinstatement of CPP through its projections to the lCeAPKCδ and ovBNSTPKCδ, respectively.

Exceptional Early Jurassic fossils with leathery eggs shed light on dinosaur reproductive biology.

Our understanding of pre-Cretaceous dinosaur reproduction is hindered by a scarcity of evidence within fossil records. Here we report three adult skeletons and five clutches of embryo-containing eggs of a new sauropodomorph from the Lower Jurassic of southwestern China, displaying several significant reproductive features that are either unknown or unlike other early-diverging sauropodomorphs, such as relatively large eggs with a relatively thick calcareous shell formed by prominent mammillary cones, synchronous hatching and a transitional prehatching posture between the crocodilians and living birds. Most significantly, these Early Jurassic fossils provide strong evidence for the earliest known leathery eggs. Our comprehensive quantitative analyses demonstrate that the first dinosaur eggs were probably leathery, elliptical and relatively small, but with relatively long eggshell units, and that along the line to living birds, the most significant change in reptilian egg morphology occurred early in theropod evolution rather than near the origin of Aves.

Nanobubbles improve peroxymonosulfate-based advanced oxidation: High efficiency, low toxicity/cost, and novel collaborative mechanism.

Cl- activated peroxymonosulfate (PMS) oxidation technology can effectively degrade pollutants, but the generation of chlorinated disinfection byproducts (DBPs) limits the application of this technology in water treatment. In this study, a method of nanobubbles (NBs) synergistic Cl-/PMS system was designed to try to improve this technology. The results showed the synergistic effects of NBs/Cl-/PMS were significant and universal while its upgrade rate was from 12.89% to 34.97%. Moreover, the synergistic effects can be further improved by increasing the concentration and Zeta potential of NBs. The main synergistic effects of NBs/Cl-/PMS system were due to the electrostatic attraction of negatively charged NBs to Na+ from NaCl, K+ from PMS, and H+ from phenol, which acted as a "bridge" between Cl- and HSO5- as well as phenol and Cl-/HSO5-, increasing active substance concentration. In addition, the addition of NBs completely changed the oxidation system of Cl-/PMS from one that increases environmental toxicity to one that reduces it. The reason was that the electrostatic attraction of NBs changed the active sites and degradation pathway of phenol, greatly reducing the production of highly toxic DBPs. This study developed a novel environmentally friendly oxidation technology, which provides an effective strategy to reduce the generation of DBPs in the Cl-/PMS system.

Highly Multiplexing, Throughput and Efficient Single-Cell Protein Analysis with Digital Microfluidics.

Proteins as crucial components of cells are responsible for the majority of cellular processes. Sensitive and efficient protein detection enables a more accurate and comprehensive investigation of cellular phenotypes and life activities. Here, a protein sequencing method with high multiplexing, high throughput, high cell utilization, and integration based on digital microfluidics (DMF-Protein-seq) is proposed, which transforms protein information into DNA sequencing readout via DNA-tagged antibodies and labels single cells with unique cell barcodes. In a 184-electrode DMF-Protein-seq system, ≈1800 cells are simultaneously detected per experimental run. The digital microfluidics device harnessing low-adsorbed hydrophobic surface and contaminants-isolated reaction space supports high cell utilization (>90%) and high mapping reads (>90%) with the input cells ranging from 140 to 2000. This system leverages split&pool strategy on the DMF chip for the first time to overcome DMF platform restriction in cell analysis throughput and replace the traditionally tedious bench-top combinatorial barcoding. With the benefits of high efficiency and sensitivity in protein analysis, the system offers great potential for cell classification and drug monitoring based on protein expression at the single-cell level.

Direct and Inverse Spin Splitting Effects in Altermagnetic RuO2.

Recently, the altermagnetic materials with spin splitting effect (SSE), have drawn significant attention due to their potential to the flexible control of the spin polarization by the Néel vector. Here, the direct and inverse altermagnetic SSE (ASSE) in the (101)-oriented RuO2 film with the tilted Néel vector are reported. First, the spin torque along the x-, y-, and z-axis is detected from the spin torque-induced ferromagnetic resonance (ST-FMR), and the z-spin torque emerges when the electric current is along the [010] direction, showing the anisotropic spin splitting of RuO2. Further, the current-induced modulation of damping is used to quantify the damping-like torque efficiency (ξDL) in RuO2/Py, and an anisotropic ξDL is obtained and maximized for the current along the [010] direction, which increases with the reduction of the temperature, indicating the present of ASSE. Next, by way of spin pumping measurement, the inverse altermagnetic spin splitting effect (IASSE) is studied, which also shows a crystal direction-dependent anisotropic behavior and temperature-dependent behavior. This work gives a comprehensive study of the direct and inverse ASSE effects in the altermagnetic RuO2, inspiring future altermagnetic materials and devices with flexible control of spin polarization.

Epitaxial Growth of CsPbBr3 Pyramids/CdS Nanobelt Heterostructures for High-Performance Photodetectors.

Perovskites have great potential for optoelectronic applications due to their high photoluminescence quantum yield, large absorption coefficient, great defect tolerance, and adjustable band gap. Perovskite heterostructures may further enhance the performance of optoelectronic devices. So far, however, most of perovskite heterostructures are fabricated by mechanical stacking or spin coating, which could introduce a large number of defects or impurities at the heterointerface owing to the random stacking process. Herein, we report the epitaxial growth of CsPbBr3 pyramids/CdS nanobelt heterostructures via a 2-step vapor deposition route. The CsPbBr3 triangular pyramids are well aligned on the surface of CdS nanobelts with the epitaxial relationships of (0-22)CsPbBr3||(1-20)CdS and (-211)CsPbBr3||(002)CdS. Time-resolved photoluminescence results reveal that effective charge transfer occurred at the heterointerface, which can be attributed to the type-II band arrangement. Theoretical simulations reveal that the unique CsPbBr3 pyramids/CdS nanobelt structure facilitates diminishing the reflection losses and enhancing the light absorption. The photodetector based on these CsPbBr3 pyramids/CdS nanobelt heterostructures exhibited an ultrahigh photoswitching ratio of 2.14 × 105, a high responsivity up to 4.07 × 104 A/W, a high detectivity reaching 1.36 × 1013 Jones, fast photoresponses (τrise = 472 µs and τdecay = 894 µs), low dark current, and suppressed hysteresis.

A novel membrane-free electrochemical separation-filtering crystallization coupling process for treating circulating cooling water.

The traditional electrochemical descaling process exhibits drawbacks, including low OH- utilization efficiency, constrained cathode deposition area, and protracted homogeneous precipitation time. Consequently, this study introduces a novel membrane-free electrochemical separation-filtering crystallization (MFES-FC) coupling process to treat circulating cooling water (CCW). In the membrane-free electrochemical separation (MFES) system, OH- is rapidly extracted by pump suction from the porous cathode boundary layer solution, preventing neutralization with H+, thereby enhancing the removal of Ca2+ and Mg2+. Experimental results indicate that the pH of the pump suction water can swiftly increase from 8.13 to 11.42 within 10 min. Owing to the high supersaturation of the pump suction water, this study couples the MFES with a filtration crystallization (FC) system that employs activated carbon as the medium. This approach captures scale particles to enhance water quality and expedites the homogeneous precipitation of hardness ions, shortening the treatment time while further augmenting the removal rate. After the MFES-FC treatment, the single-pass removal rates for total hardness, Ca2+ hardness, Mg2+ hardness, and alkalinity in the effluent reached 92 %, 97 %, 64 %, and 67 %, respectively, with turbidity of 3 NTU, current efficiency of 86.6 %, and energy consumption of 7.19 kWh·kg-1 CaCO3. This coupling process facilitates an effective removal of hardness and alkalinity at a comparatively low cost, offering a new reference and inspiration for advancements in electrochemical descaling technology.

Systematic Investigation of the Trafficking of Glycoproteins on the Cell Surface.

Glycoproteins located on the cell surface play a pivotal role in nearly every extracellular activity. N-glycosylation is one of the most common and important protein modifications in eukaryotic cells, and it often regulates protein folding and trafficking. Glycosylation of cell-surface proteins undergoes meticulous regulation by various enzymes in the endoplasmic reticulum (ER) and the Golgi, ensuring their proper folding and trafficking to the cell surface. However, the impacts of protein N-glycosylation, N-glycan maturity, and protein folding status on the trafficking of cell-surface glycoproteins remain to be explored. In this work, we comprehensively and site-specifically studied the trafficking of cell-surface glycoproteins in human cells. Integrating metabolic labeling, bioorthogonal chemistry, and multiplexed proteomics, we investigated 706 N-glycosylation sites on 396 cell-surface glycoproteins in monocytes, either by inhibiting protein N-glycosylation, disturbing N-glycan maturation, or perturbing protein folding in the ER. The current results reveal their distinct impacts on the trafficking of surface glycoproteins. The inhibition of protein N-glycosylation dramatically suppresses the trafficking of many cell-surface glycoproteins. The N-glycan immaturity has more substantial effects on proteins with high N-glycosylation site densities, while the perturbation of protein folding in the ER exerts a more pronounced impact on surface glycoproteins with larger sizes. Furthermore, for N-glycosylated proteins, their trafficking to the cell surface is related to the secondary structures and adjacent amino acid residues of glycosylation sites. Systematic analysis of surface glycoprotein trafficking advances our understanding of the mechanisms underlying protein secretion and surface presentation.

Size-Dependent Catalysis in Fenton-like Chemistry: From Nanoparticles to Single Atoms.

State-of-the-art Fenton-like reactions are crucial in advanced oxidation processes (AOPs) for water purification. This review explores the latest advancements in heterogeneous metal-based catalysts within AOPs, covering nanoparticles (NPs), single-atom catalysts (SACs), and ultra-small atom clusters. A distinct connection between the physical properties of these catalysts, such as size, degree of unsaturation, electronic structure, and oxidation state, and their impacts on catalytic behavior and efficacy in Fenton-like reactions. In-depth comparative analysis of metal NPs and SACs is conducted focusing on how particle size variations and metal-support interactions affect oxidation species and pathways. The review highlights the cutting-edge characterization techniques and theoretical calculations, indispensable for deciphering the complex electronic and structural characteristics of active sites in downsized metal particles. Additionally, the review underscores innovative strategies for immobilizing these catalysts onto membrane surfaces, offering a solution to the inherent challenges of powdered catalysts. Recent advances in pilot-scale or engineering applications of Fenton-like-based devices are also summarized for the first time. The paper concludes by charting new research directions, emphasizing advanced catalyst design, precise identification of reactive oxygen species, and in-depth mechanistic studies. These efforts aim to enhance the application potential of nanotechnology-based AOPs in real-world wastewater treatment.

Tooth replacement in the early-diverging neornithischian Jeholosaurus shangyuanensis and implications for dental evolution and herbivorous adaptation in Ornithischia.

BACKGROUND: Tooth replacement patterns of early-diverging ornithischians, which are important for understanding the evolution of the highly specialized dental systems in hadrosaurid and ceratopsid dinosaurs, are poorly known. The early-diverging neornithischian Jeholosaurus, a small, bipedal herbivorous dinosaur from the Early Cretaceous Jehol Biota, is an important taxon for understanding ornithischian dental evolution, but its dental morphology was only briefly described previously and its tooth replacement is poorly known. RESULTS: CT scanning of six specimens representing different ontogenetic stages of Jeholosaurus reveals significant new information regarding the dental system of Jeholosaurus, including one or two replacement teeth in nearly all alveoli, relatively complete tooth resorption, and an increase in the numbers of alveoli and replacement teeth during ontogeny. Reconstructions of Zahnreihen indicate that the replacement pattern of the maxillary dentition is similar to that of the dentary dentition but with a cyclical difference. The maxillary tooth replacement rate in Jeholosaurus is probably 46 days, which is faster than that of most other early-diverging ornithischians. During the ontogeny of Jeholosaurus, the premaxillary tooth replacement rate slows from 25 days to 33 days with similar daily dentine formation. CONCLUSIONS: The tooth replacement rate exhibits a decreasing trend with ontogeny, as in Alligator. In a phylogenetic context, fast tooth replacement and multi-generation replacement teeth have evolved at least twice independently in Ornithopoda, and our analyses suggest that the early-diverging members of the major ornithischian clades exhibit different tooth replacement patterns as an adaption to herbivory.

Atomic-level Engineered Cobalt Catalysts for Fenton-Like Reactions: Synergy of Single Atom Metal Sites and Nonmetal-bonded Functionalities.

Single atom catalysts (SACs) are atomic-level-engineered materials with high intrinsic activity. Catalytic centers of SACs are typically the transition metal (TM)-nonmetal coordination sites, while the functions of co-existing non-TM-bonded functionalities are usually overlooked in catalysis. Herein, we reported the scalable preparation of carbon-supported cobalt-anchored SACs (CoCN) with controlled Co-N sites and free functional N species. We first systematically study the role of metal and nonmetal bonded functionalities in the SACs for peroxymonosulfate (PMS)-driven Fenton-like reactions, revealing their contribution to performance improvement and pathway steering. Experiments and computations demonstrate that the Co-N3C coordination plays a vital role in the formation of a surface-confined PMS* complex to trigger the electron transfer pathway and promote kinetics because of the optimized electronic state of Co centers, while the non-metal-coordinated graphitic N sites act as preferable pollutant adsorption sites and additional PMS activation sites to accelerate electron transfer. Synergistically, CoCN exhibits ultrahigh activity in PMS activation for p-hydroxybenzoic acid oxidation, achieving complete degradation within 10 min with an ultrahigh turnover frequency of 0.38 min-1, surpassing most reported materials. These findings offer new insights into the versatile functions of N species in SACs and inspire rational design of high-performance catalysts in complicated heterogeneous systems. This article is protected by copyright. All rights reserved.

Insights into the efficient water treatment over N-doped carbon nanosheets with layered minerals as template: The role of interfacial electron tunneling and transfer.

Peroxymonosulfate (PMS) oxidation reactions have been extensively studied recently. Due to the high material cost and low catalytic capability, PMS oxidation technology cannot be effectively applied in an industrial water treatment process. In this work, we developed a modification strategy based on enhancing the neglected electron tunneling effect to optimize the intrinsic electron transport process of the catalyst. The 2D nitrogen-doped carbon-based nanosheets with small interlayer spacing were prepared by self-polymerization of dopamine hydrochloride inserted into the natural layered bentonite template. Systematic characterizations confirmed that the smaller layer spacing in the 2D nitride-doped carbon-based nanosheets reduces the depletion layer width. The weak electronic shielding effect derived by the small layer spacing on the material subsurface enhanced the bulk electron tunneling effect. More bulk electrons could be migrated to the catalyst surface to activate PMS molecules. The PMS activation system showed ultrafast oxidation capability to degrade organic pollutants and strong ability to resist interference from environmental matrixes due to the optimized electron transfer process. Furthermore, the developed membrane reactor exhibited strong catalytic stability during the continuous degradation of P-Chlorophenol (CP).

The Effect of Pixel Design and Operation Conditions on Linear Output Range of 4T CMOS Image Sensors.

We analyze several factors that affect the linear output range of CMOS image sensors, including charge transfer time, reset transistor supply voltage, the capacitance of integration capacitor, the n-well doping of the pinned photodiode (PPD) and the output buffer. The test chips are fabricated with 0.18 µm CMOS image sensor (CIS) process and comprise six channels. Channels B1 and B2 are 10 µm pixels and channels B3-B6 are 20 µm pixels, with corresponding pixel arrays of 1 × 2560 and 1 × 1280 respectively. The floating diffusion (FD) capacitance varies from 10 fF to 23.3 fF, and two different designs were employed for the n-well doping in PPD. The experimental results indicate that optimizing the FD capacitance and PPD design can enhance the linear output range by 37% and 32%, respectively. For larger pixel sizes, extending the transfer gate (TG) sampling time leads to an increase of over 60% in the linear output range. Furthermore, optimizing the design of the output buffer can alleviate restrictions on the linear output range. The lower reset voltage for noise reduction does not exhibit a significant impact on the linear output range. Furthermore, these methods can enhance the linear output range without significantly amplifying the readout noise. These findings indicate that the linear output range of pixels is not only influenced by pixel design but also by operational conditions. Finally, we conducted a detailed analysis of the impact of PPD n-well doping concentration and TG sampling time on the linear output range. This provides designers with a clear understanding of how nonlinearity is introduced into pixels, offering valuable insight in the design of highly linear pixels.

Selective and ultrafast oxidation of multiple pollutants by biomorphic diatomite-based catalyst and stable catalytic Fenton-like membrane: Degradation behavior and mechanism analysis.

Carbon-driven advanced oxidations show great potential in water purification, but regulating structures and properties of carbon-based catalysts to achieve ultrafast Fenton-like reactions remains challenging. Herein, a biomorphic diatomite-based catalyst (BD-C) with Si-O doping was prepared using natural diatomite as silicon source and porous template. The results showed that the metal-free BD-C catalyst exhibited ultrafast oxidation performances (0.95-2.58 min-1) towards a variety of pollutants in PMS-based Fenton-like reaction, with the Fenton-like activity of metal-free catalyst comparable to metal-based catalysts or even single-atom catalysts. Pollutants (e.g., CP, BPA, TC, and PCM) with electron-donating groups exhibited extremely low PMS decomposition with overwhelmed electron transfer process (ETP), while high PMS consumption was induced by the addition of electron-withdrawing pollutants (e.g., MNZ and ATZ), which was dominated by radical oxidation. The BD-C/PMS system also showed a high ability to resist the environmental interference. In-depth theoretical investigations demonstrated that the coordination of Si-O can lower the potential barrier of PMS activation for accelerating the generation of radicals, and also promote the electron transfer from pollutants to the BD-C/PMS complexes. In addition, BD-C was deposited onto a polytetrafluoroethylene membrane (PTFEM) with 100% of pollutants removal over 10 h, thereby revealing the promising prospects of utilizing BD-C for practical applications.

GSNOR overexpression enhances CAR-T cell stemness and anti-tumor function by enforcing mitochondrial fitness.

Chimeric antigen receptor-T (CAR-T) cell has been developed as a promising agent for patients with refractory or relapsed lymphoma and leukemia, but not all the recipients could achieve a long-lasting remission. The limited capacity of in vivo expansion and memory differentiation post activation is one of the major reasons for suboptimal CAR-T therapeutic efficiency. Nitric oxide (NO) plays multifaceted roles in mitochondrial dynamics and T cell activation, but its function on CAR-T cell persistence and anti-tumor efficacy remains unknown. Herein, we found the continuous signaling from CAR not only promotes excessive NO production, but also suppressed S-nitrosoglutathione reductase (GSNOR) expression in T cells, which collectively led to increased protein S-nitrosylation, resulting in impaired mitochondrial fitness and deficiency of T cell stemness. Intriguingly, enforced expression of GSNOR promoted memory differentiation of CAR-T cell after immune activation, rendered CAR-T better resistance to mitochondrial dysfunction, further enhanced CAR-T cell expansion and anti-tumor capacity in vitro and in a mouse tumor model. Thus, we revealed a critical role of NO in restricting CAR-T cell persistence and functionality, and defined that GSNOR overexpression may provide a solution to combat NO stress and render patients with more durable protection from CAR-T therapy.

Trachelogenin alleviates osteoarthritis by inhibiting osteoclastogenesis and enhancing chondrocyte survival.

BACKGROUND: Osteoarthritis (OA) is a prevalent global health concern associated with the loss of articular cartilage and subchondral bone. The lack of disease-modifying drugs for OA necessitates the exploration of novel therapeutic options. Our previous study has demonstrated that traditional Chinese medical herb Trachelospermum jasminoides (Lindl.) Lem. extract suppressed osteoclastogenesis and identified trachelogenin (TCG) as a representative compound. Here, we delved into TCG's potential to alleviate OA. METHODS: We initially validated the in vivo efficacy of TCG in alleviating OA using a rat OA model. Subsequently, we isolated primary bone marrow-derived macrophages in vitro to investigate TCG's impact on osteoclastogenesis. We further employed a small molecule pull-down assay to verify TCG's binding target within osteoclasts. Finally, we isolated primary mouse chondrocytes in vitro to study TCG's regulatory effects and mechanisms on chondrocyte survival. RESULTS: TCG preserved subchondral bone integrity and protected articular cartilage in a rat OA model. Subsequently, in vitro experiments unveiled TCG's capability to inhibit osteoclastogenesis and function through binding to Ras association proximate 1 (Rap1) and inhibiting its activation. Further study demonstrated that TCG inhibited Rap1/integrin αvß3/c-Src/Pyk2 signaling cascade, and consequently led to failed F-actin ring formation. Besides, TCG promoted the proliferation of mouse primary chondrocytes while suppressing apoptosis in vitro. This is attributed to TCG's ability to upregulate HIF1α, thereby promoting glycolysis. CONCLUSION: TCG exerted inhibitory effects on osteoclastogenesis through binding to Rap1 and inhibiting Rap1 activation, consequently preventing subchondral bone loss. Moreover, TCG enhanced chondrocyte survival by upregulating HIF1α and promoting glycolysis. These dual mechanisms collectively provide a novel approach to prevented against cartilage degradation.

Mediated Peroxymonosulfate Activation at the Single Atom Fe-N3 O1 Sites: Synergistic Degradation of Antibiotics by Two Non-Radical Pathways.

The activation of persulfates to degrade refractory organic pollutants is a hot issue in advanced oxidation right now. Here, it is reported that single-atom Fe-incorporated carbon nitride (Fe-CN-650) can effectively activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. Through some characterization techniques and DFT calculation, it is proved that Fe single atoms in Fe-CN-650 exist mainly in the form of Fe-N3 O1 coordination, and Fe-N3 O1 exhibited better affinity for PMS than the traditional Fe-N4 structure. The degradation rate constant of SMX in the Fe-CN-650/PMS system reached 0.472 min-1 , and 90.80% of SMX can still be effectively degraded within 10 min after five consecutive recovery cycles. The radical quenching experiment and electrochemical analysis confirm that the pollutants are mainly degraded by two non-radical pathways through 1 O2 and Fe(IV)═O induced at the Fe-N3 O1 sites. In addition, the intermediate products of SMX degradation in the Fe-CN-650/PMS system show toxicity attenuation or non-toxicity. This study offers valuable insights into the design of carbon-based single-atom catalysts and provides a potential remediation technology for the optimum activation of PMS to disintegrate organic pollutants.

Macrolide sesquiterpene pyridine alkaloids from Celastrus monospermus and evaluation of their immunosuppressive and anti-osteoclastogenesis activities.

Phytochemical investigation of the stems of Celastrus monospermus Roxb enabled isolation and identification of fifteen new macrolide sesquiterpene pyridine alkaloids (1-15) along with five known analogues. Their structures were elucidated by comprehensive spectroscopic analysis (NMR, HRESIMS, IR, UV), chemical hydrolysis, and single crystal X-ray diffraction analysis. Bioassay of the abundant isolates revealed that seven compounds inhibited the proliferation of B lymphocytes with IC50 values ranging between 1.4 and 19.9 µM. Among them, celasmondine C (3) could significantly promote the apoptosis of activated B lymphocyte, especially late-stage apoptosis. Besides, compounds 3, 16, and 20 exhibited potent suppression of osteoclast formation at a concentration of 1.0 µM. This investigation enriched the chemical diversity of macrolide sesquiterpene pyridine alkaloids, and supported evidence for the development of new immunosuppressive and anti-osteoclastogenesis agents.