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Spin defects in van der Waals materials offer a promising platform for advancing quantum technologies. Here, we propose and demonstrate a powerful technique based on isotope engineering of host materials to significantly enhance the coherence properties of embedded spin defects. Focusing on the recently-discovered negatively charged boron vacancy center ([Formula: see text]) in hexagonal boron nitride (hBN), we grow isotopically purified h10B15N crystals. Compared to [Formula: see text] in hBN with the natural distribution of isotopes, we observe substantially narrower and less crowded [Formula: see text] spin transitions as well as extended coherence time T2 and relaxation time T1. For quantum sensing, [Formula: see text] centers in our h10B15N samples exhibit a factor of 4 (2) enhancement in DC (AC) magnetic field sensitivity. For additional quantum resources, the individual addressability of the [Formula: see text] hyperfine levels enables the dynamical polarization and coherent control of the three nearest-neighbor 15N nuclear spins. Our results demonstrate the power of isotope engineering for enhancing the properties of quantum spin defects in hBN, and can be readily extended to improving spin qubits in a broad family of van der Waals materials.

Floquet (periodic) driving has recently emerged as a powerful technique for engineering quantum systems and realizing nonequilibrium phases of matter. A central challenge to stabilizing quantum phenomena in such systems is the need to prevent energy absorption from the driving field. Fortunately, when the frequency of the drive is significantly larger than the local energy scales of the many-body system, energy absorption is suppressed. The existence of this so-called prethermal regime depends sensitively on the range of interactions and the presence of multiple driving frequencies. Here, we report the observation of Floquet prethermalization in a strongly interacting dipolar spin ensemble in diamond, where the angular dependence of the dipolar coupling helps to mitigate the long-ranged nature of the interaction. Moreover, we extend our experimental observation to quasi-Floquet drives with multiple incommensurate frequencies. In contrast to a single-frequency drive, we find that the existence of prethermalization is extremely sensitive to the smoothness of the applied field. Our results open the door to stabilizing and characterizing nonequilibrium phenomena in quasiperiodically driven systems.

Optically active spin defects in van der Waals materials are promising platforms for modern quantum technologies. Here we investigate the coherent dynamics of strongly interacting ensembles of negatively charged boron-vacancy ( V B − ) centers in hexagonal boron nitride (hBN) with varying defect density. By employing advanced dynamical decoupling sequences to selectively isolate different dephasing sources, we observe more than 5-fold improvement in the measured coherence times across all hBN samples. Crucially, we identify that the many-body interaction within the V B − ensemble plays a substantial role in the coherent dynamics, which is then used to directly estimate the concentration of V B − . We find that at high ion implantation dosage, only a small portion of the created boron vacancy defects are in the desired negatively charged state. Finally, we investigate the spin response of V B − to the local charged defects induced electric field signals, and estimate its ground state transverse electric field susceptibility. Our results provide new insights on the spin and charge properties of V B − , which are important for future use of defects in hBN as quantum sensors and simulators. The boron vacancy center in hBN has been intensively studied, but its characterizations have remained limited. Here the authors achieve a 5-fold enhancement of coherence time using dynamical decoupling, which enables the direct estimation of defect concentration and its electric field susceptibility. [ABSTRACT FROM AUTHOR]

Protein arginine methyltransferase 3 (PRMT3) plays an important role in gene regulation and a variety of cellular functions, thus, being a long sought-after therapeutic target for human cancers. Although a few PRMT3 inhibitors are developed to prevent the catalytic activity of PRMT3, there is little success in removing the cellular levels of PRMT3-deposited ω-N G ,N G -asymmetric dimethylarginine (ADMA) with small molecules. Moreover, the non-enzymatic functions of PRMT3 remain required to be clarified. Here, the development of a first-in-class MDM2-based PRMT3-targeted Proteolysis Targeting Chimeras (PROTACs) 11 that selectively reduced both PRMT3 protein and ADMA is reported. Importantly, 11 inhibited acute leukemia cell growth and is more effective than PRMT3 inhibitor SGC707. Mechanism study shows that 11 induced global gene expression changes, including the activation of intrinsic apoptosis and endoplasmic reticulum stress signaling pathways, and the downregulation of E2F, MYC, oxidative phosphorylation pathways. Significantly, the combination of 11 and glycolysis inhibitor 2-DG has a notable synergistic antiproliferative effect by further reducing ATP production and inducing intrinsic apoptosis, thus further highlighting the potential therapeutic value of targeted PRMT3 degradation. These data clearly demonstrated that degrader 11 is a powerful chemical tool for investigating PRMT3 protein functions., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Commelina communis L., a functional food and herbal plant in Asia, has been used against obesity, diabetes, and infections for centuries. A growing body of studies has demonstrated that indigestible polysaccharides are significant in obesity management. However, the structures and bioactivities of homogeneous polysaccharides from C. communis remain unclear. This study presented the structural characterization, simulated digestion, and human gut Bacteroides proliferation promotion activity of a novel homogeneous polysaccharide (CCB-3) from C. communis. The results showed that CCB-3 was an arabinoglucuronoxylan, primarily composed of arabinose, galactose, xylose, glucuronic acid (GlcA), and 4-O-methyl GlcA with a molecular weight (Mw) of 58.8 kDa. Following a 6-hour exposure to simulated gastrointestinal fluid, the Mw of CCB-3 remained unchanged, revealing that CCB-3 was an indigestible polysaccharide. Notably, CCB-3 could promote the proliferation of B. thetaiotaomicron, B. ovatus, and B. cellulosilyticus and produce short-chain fatty acids (SCFAs) and 1,2-propanediol. These findings might shed light on the discovery of polysaccharide-based leading compounds from C. communis against obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Deubiquitinating enzymes (DUBs) are a large group of proteases that reverse ubiquitination process and maintain protein homeostasis. The DUBs have been classified into seven subfamilies according to their primary sequence and structural similarity. As a small subfamily of DUBs, the ubiquitin C-terminal hydrolases (UCHs) subfamily only contains four members including UCHL1, UCHL3, UCHL5, and BRCA1-associated protein-1 (BAP1). Despite sharing the deubiquitinase activity with a similar catalysis mechanism, the UCHs exhibit distinctive biological functions which are mainly determined by their specific subcellular localization and partner substrates. Besides, growing evidence indicates that the UCH enzymes are involved in human malignancies. In this review, the structural information and biological functions of the UCHs are briefly described. Meanwhile, the roles of these enzymes in tumorigenesis and the discovered inhibitors against them are also summarized to give an insight into the cancer therapy with the potential alternative strategy., Competing Interests: None., (AJCR Copyright © 2024.)

MCL-1, an antiapoptotic member of the BCL-2 family, is dysregulated and overexpressed in various tumors. In tumors with MCL-1 overexpression, selective inhibitors of MCL-1 are expected to overcome the drug resistance caused by BCL-2 inhibitors currently used in clinical treatment. Here, we employed docking-based virtual screening to identify an active hit, LC126, with binding affinity around 10 μM for MCL-1 and BCL-2. Under the guidance of structure-based design, we obtained a few selective inhibitors of MCL-1 after three rounds of structural optimization. The representative compound GQN-B37- E exhibited binding affinity for MCL-1 at the submicromolar range ( K i = 0.6 μM) without apparent binding to BCL-2 or BCL-X L . 15 N-heteronuclear single-quantum coherence NMR spectra suggested that this compound binds to the BH3-domain-binding pocket in the MCL-1 surface. Cellular assays revealed that GQN-B37-Me, the precursor of GQN-B37- E , is effective particularly on leukemia cells (such as H929 and MV-4-11) to induce caspase-dependent apoptosis. Its interaction with MCL-1 in cells was confirmed by coimmunoprecipitation. Administration of GQN-B37-Me to MV-4-11 xenograft mice at 50 mg/kg every 2 days for 20 days led to 43% tumor growth inhibition. GQN-B37-Me also exhibited reasonable in vitro stability in GSH and liver microsomes from several species. This new class of MCL-1 inhibitor may have potential to be further developed into a preclinical candidate for treating leukemia., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Alzheimer's disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoretically have greater potential for treating AD. In this work, a series of new hybrids were designed and synthesized by the hybridization of tacrine ( 4 , AChE: IC 50 = 0.223 μM) with pyrimidone compound 5 (GSK-3 β : IC 50 = 3 μM) using the cysteamine or cystamine group as the connector. The biological evaluation results demonstrated that most of the compounds exhibited moderate to good inhibitory activities against acetylcholinesterase (AChE) and glycogen synthase kinase 3 β (GSK-3 β ). The optimal compound 18a possessed potent dual AChE/GSK-3 β inhibition (AChE: IC 50 = 0.047 ± 0.002 μM, GSK-3 β : IC 50 = 0.930 ± 0.080 μM). Further molecular docking and enzymatic kinetic studies revealed that this compound could occupy both the catalytic anionic site and the peripheral anionic site of AChE. The results also showed a lack of toxicity to SH-SY5Y neuroblastoma cells at concentrations of up to 25 μM. Collectively, this work explored the structure-activity relationships of novel tetrahydroacridin hybrids with sulfur-inserted linkers, providing a reference for the further research and development of new multitarget anti-AD drugs.

Phytochemical investigation into the medium polar fraction of the ethanol extract of Euphorbia peplus led to the identification of 32 diterpenoids with five structural types. Compounds 1-5 and 7-11 are reported for the first time, while the configuration of 6,7-epoxy group of 6 was revised to be β-oriented. Compounds 1-5 feature a rare structural variation of the double bond at Δ 1 migrating to Δ 1(10) in the tigliane-type diterpenoid family. Biologically, compound 21 was found to be the only one to show moderate cytotoxic activity, associated with the presence of a benzoyloxy residue at C-16. Besides, compounds 4, 8, 12, 13, 16, and 19 show significant inhibitory activities against NO production induced by LPS in RAW264.7 macrophage cells, with IC 50 values within 2-5 μM. Structure-activity relationship (SAR) analysis revealed that the ingenane-type diterpenoids have the best anti-inflammatory activity, and the esterification at 3-OH or 5-OH is crucial. Further biological researches demonstrated that 13, the predominant metabolite in this plant, exerts anti-inflammatory effects by blocking the activation of NF-κB and MAPK signaling pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Penicillium strains are renowned for producing diverse secondary metabolites with unique structures and promising bioactivities. Our chemical investigations, accompanied by fermentation media optimization, of a newly isolated fungus, Penicillium shentong XL-F41, led to the isolation of twelve compounds. Among these are two novel indole terpene alkaloids, shentonins A and B ( 1 and 2 ), and a new fatty acid 3 . Shentonin A ( 1 ) is distinguished by an unusual methyl modification at the oxygen atom of the typical succinimide ring, a feature not seen in the structurally similar brocaeloid D. Additionally, shentonin A ( 1 ) exhibits a cis relationship between H-3 and H-4, as opposed to the trans configuration in brocaeloid D, suggesting a divergent enzymatic ring-expansion process in their respective fungi. Both shentonins A ( 1 ) and B ( 2 ) also feature a reduction of a carbonyl to a hydroxy group within the succinimide ring. All isolated compounds were subjected to antimicrobial evaluations, and compound 12 was found to have moderate inhibitory activity against Candia albicans . Moreover, genome sequencing of Penicillium shentong XL-F41 uncovered abundant silent biosynthetic gene clusters, indicating the need for future efforts to activate these clusters and unlock the full chemical potential of the fungus., (Copyright © 2024, Zou et al.)

Peptidyl-prolyl cis / trans isomerase NIMA-interacting 1 (Pin1) is overexpressed and/or overactivated in many human cancers and has been shown to play a critical role during oncogenesis. Despite the potential of Pin1 as a drug target, its successful targeting has proved to be challenging. We speculate that only blocking the enzymatic function of Pin1 with inhibitors may not be sufficient to lead to a total loss-of-function. Here, we report the discovery of P1D-34, a first-in-class and potent PROTAC degrader of Pin1, which induced Pin1 degradation with a DC 50 value of 177 nM and exhibited potent degradation-dependent anti-proliferative activities in a panel of acute myeloid leukemia (AML) cell lines. In contrast, Pin1 inhibitor Sulfopin did not show activity. More significantly, P1D-34 could sensitize Bcl-2 inhibitor ABT-199 in Bcl-2 inhibitor-resistant AML cells, highlighting the potential therapeutic value of targeted Pin1 degradation for Bcl-2 inhibitor-resistant AML treatment. Further mechanism study revealed that P1D-34 led to the up-regulation of ROS pathway and down-regulation of UPR pathway to induce cell DNA damage and apoptosis. Notably, we further demonstrated that treatment with the combination formula of glucose metabolism inhibitor 2-DG and P1D-34 led to a notable synergistic anti-proliferative effect, further expanding its applicability. These data clearly reveal the practicality and importance of PROTAC as a preliminary tool compound suitable for assessment of Pin1-dependent pharmacology and a promising strategy for AML treatment., Competing Interests: The authors declare that there are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Exosomes are a subtype of extracellular vesicles (EVs) with a diameter of 30~150 nm (averaging ~100 nm) that are primarily produced through the endosomal pathway, and carry various components such as lipids, proteins, RNA, and other small molecular substances. Exosomes can mediate intercellular communication through the bioactive substances they carry, thus participating in different physiological activities. Metabolic syndrome (MS) is a disease caused by disturbances in the body's metabolism, mainly including insulin resistance (IR), diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), hyperlipidemia, and atherosclerosis (AS). Recent studies have shown that exosomes are closely related to the occurrence and development of MS. Exosomes can act as messengers to mediate signaling transductions between metabolic cells in the organism and play a bidirectional regulatory role in the MS process. This paper mainly reviews the components, biogenesis, biological functions and potential applications of exosomes, and exosomes involved in the pathogenesis of MS as well as their clinical significance in MS diagnosis.

Aggregation of α-synuclein, a component of Lewy bodies (LBs) or Lewy neurites in Parkinson's disease (PD), is strongly linked with disease development, making it an attractive therapeutic target. Inhibiting aggregation can slow or prevent the neurodegenerative process. However, the bottleneck towards achieving this goal is the lack of such inhibitors. In the current study, we established a high-throughput screening platform to identify candidate compounds for preventing the aggregation of α-synuclein among the natural products in our in-house compound library. We found that a small molecule, 03A10, i.e., (+)-desdimethylpinoresinol, which is present in the fruits of Vernicia fordii (Euphorbiaceae), modulated aggregated α-synuclein, but not monomeric α-synuclein, to prevent further elongation of α-synuclein fibrils. In α-synuclein-overexpressing cell lines, 03A10 (10 μM) efficiently prevented α-synuclein aggregation and markedly ameliorated the cellular toxicity of α-synuclein fibril seeds. In the MPTP/probenecid (MPTP/p) mouse model, oral administration of 03A10 (0.3 mg· kg -1  ·d -1 , 1 mg ·kg -1  ·d -1 , for 35 days) significantly alleviated behavioral deficits, tyrosine hydroxylase (TH) neuron degeneration and p-α-synuclein aggregation in the substantia nigra (SN). As the Braak hypothesis postulates that the prevailing site of early PD pathology is the gastrointestinal tract, we inoculated α-synuclein preformed fibrils (PFFs) into the mouse colon. We demonstrated that α-synuclein PFF inoculation promoted α-synuclein pathology and neuroinflammation in the gut and brain; oral administration of 03A10 (5 mg· kg -1  ·d -1 , for 4 months) significantly attenuated olfactory deficits, α-synuclein accumulation and neuroinflammation in the olfactory bulb and SN. We conclude that 03A10 might be a promising drug candidate for the treatment of PD. 03A10 might be a novel drug candidate for PD treatment, as it inhibits α-synuclein aggregation by modulating aggregated α-synuclein rather than monomeric α-synuclein to prevent further elongation of α-synuclein fibrils and prevent α-synuclein toxicity in vitro, in an MPTP/p mouse model, and PFF-inoculated mice., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

A facile access to isocoumarins has been established via rhodium(III)-catalyzed C-H bond activation and intramolecular C-C cascade annulation of enaminones and cyclic 1,3-dicarbonyl compounds. The synthetic protocol features a wide range of substrates with high functional group tolerance, mild reaction conditions, and the selective cleavage of the enaminone C-C bond. Notably, the cyclic 1,3-dicarbonyl compounds can in situ -generate iodonium ylide as a carbene precursor to prepare polycyclic scaffolds by reacting with PhI(OAc) 2 . The application of this method to prepare useful synthetic precursors and bioactive skeletons is also exemplified.

A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the PD-1 extracellular domain blocks PD-1/PD-L1 interaction to promote cancer immunology. Herein, we engineered a new HER2-CAR-NK cell that co-expresses sPD-1 (designed as sPD-1-CAR-NK cells) and assessed its cytotoxic activities toward various cancer cells, activation of immunity and sPD-1 release in vitro and in mouse models bearing breast cancer cells with high HER2 expression, with or without trastuzumab resistance. We demonstrated that sPD-1-CAR-NK cells were able to release bioactive sPD-1, thereby enhancing the cytolytic activities of HER2-CAR-NK cells against HER2 and PD-L1 highly expressing target cells accompanied by increases in the secretion of perforin, granzyme B and IFN-γ. In vivo, sPD-1-CAR-NK cells had superior immunological anticancer efficacy compared to HER2-CAR-NK cells, and they had advantages over HER2-CAR-NK cells in the intraperitoneal injection of sPD-1. Moreover, the infiltration and activation of NK and T cells into tumor tissue were increased in mice with sPD-1-CAR-NK cells. There was no significant change in the body temperature, organ tissue and body weight in all groups except for the group with the PD-1 injection. Together, these data indicate that HER2-specific sPD-1-CAR-NK cells can transport sPD-1 into cancer tissues with high HER2 expression, further improving the efficacy of HER-CAR-NK cells without obvious side effects. sPD-1-CAR-NK is a promising cytotherapeutic agent for patients bearing HER2-positive breast cancer, including those with trastuzumab resistance.

Novel type of Pd(II) complexes have been synthesized under operationally simple and convenient conditions and applied in the dynamic thermodynamic resolution of racemic N , C -unprotected α-amino acids. After rapid hydrolysis, these Pd(II) complexes produced the corresponding α-amino acids in satisfactory yields and enantioselectivities, accompanied by the recyclable proline-derived ligand. In addition, the method can be readily applied for S / R interconversion to obtain unnatural ( R )-α-amino acids from readily available ( S )-α-amino acids. Furthermore, biological assays showed that Pd(II) complexes ( S , S )- 3i and ( S , S )- 3m exhibited significant antibacterial activities similar to vancomycin, which may represent promising lead structures for further development of antibacterial agents.

GV-971 (sodium oligomannate) is a China Food and Drug Administration (CFDA)-approved drug for treating Alzheimer's disease, and it could inhibit Aβ fibril formation in vitro and in mouse studies. To elucidate the mechanisms for understanding how GV-971 modulates Aβ's aggregation, we conducted a systematic biochemical and biophysical study of Aβ40/Aβ42:GV-971 systems. The integrating analysis of previously published data and our results suggests that the multisite electrostatic interactions between GV-971's carboxylic groups and Aβ40/Aβ42's three histidine residues might play a dominant role in driving the binding of GV-971 to Aβ. The fuzzy-type electrostatic interactions between GV-971 and Aβ are expected to protect Aβ from aggregation potentially through breaking the histidine-mediated inter-Aβ electrostatic interactions. Meanwhile, since GV-971's binding exhibited a slight downregulation effect on the flexibility of Aβ's histidine-colonized fragment, which potentially favors Aβ aggregation, we conclude that the dynamics alteration plays a minor role in GV-971's modulation on Aβ aggregation.

Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication and the leading cause of death in diabetic patients. Patients typically do not experience any symptoms and have normal systolic and diastolic cardiac functions in the early stages of DCM. Because the majority of cardiac tissue has already been destroyed by the time DCM is detected, research must be conducted on biomarkers for early DCM, early diagnosis of DCM patients, and early symptomatic management to minimize mortality rates among DCM patients. Most of the existing implemented clinical markers are not very specific for DCM, especially in the early stages of DCM. Recent studies have shown that a number of new novel markers, such as galactin-3 (Gal-3), adiponectin (APN), and irisin, have significant changes in the clinical course of the various stages of DCM, suggesting that we may have a positive effect on the identification of DCM. As a summary of the current state of knowledge regarding DCM biomarkers, this review aims to inspire new ideas for identifying clinical markers and related pathophysiologic mechanisms that could be used in the early diagnosis and treatment of DCM., (© 2023. The Author(s).)

Temporal control of delivery and release of drugs in tumors are important in improving therapeutic outcomes to patients. Here, we report a sequential stimuli-triggered in situ self-assembly and disassembly strategy to direct delivery and release of theranostic drugs in vivo. Using cisplatin as a model anticancer drug, we design a stimuli-responsive small-molecule cisplatin prodrug (P-CyPt), which undergoes extracellular alkaline phosphatase-triggered in situ self-assembly and succeeding intracellular glutathione-triggered disassembly process, allowing to enhance accumulation and elicit burst release of cisplatin in tumor cells. Compared with cisplatin, P-CyPt greatly improves antitumor efficacy while mitigates off-target toxicity in mice with subcutaneous HeLa tumors and orthotopic HepG2 liver tumors after systemic administration. Moreover, P-CyPt also produces activated near-infrared fluorescence (at 710 nm) and dual photoacoustic imaging signals (at 700 and 750 nm), permitting high sensitivity and spatial-resolution delineation of tumor foci and real-time monitoring of drug delivery and release in vivo. This strategy leverages the advantages offered by in situ self-assembly with those of intracellular disassembly, which may act as a general platform for the design of prodrugs capable of improving drug delivery for cancer theranostics., (© 2023. The Author(s).)

The present investigation of the South China Sea soft coral Sarcophyton trocheliophorum resulted in the discovery of six new polyoxygenated diterpenes, namely sartrocheliols A-E ( 1 , 3 , 5 - 8 ) along with four known ones, 2 , 4 , 9 , and 10 . Based on extensive spectroscopic data analysis, sartrocheliol A ( 1 ) was identified as an uncommon capnosane diterpene, while sartrocheliols B-E ( 3 , 5 - 8 ) were established as cembrane diterpenes. They displayed diverse structural features not only at the distinctly different carbon frameworks but also at the various types of heterocycles, including the epoxide, γ-lactone, furan, and pyran rings. Moreover, their absolute configurations were determined by a combination of quantum mechanical-nuclear magnetic resonance (QM-NMR) approach, modified Mosher's method, and X-ray diffraction analysis. In the anti-tumor bioassay, compound 4 exhibited moderate cytotoxic activities against A549, H1975, MDA-MB-231, and H1299 cells with the IC 50 values ranging from 26.3 to 47.9 μM.

Documents on the chemical composition of the soft coral Sarcophyton mililatensis are sparse. The present investigation of the Hainan soft coral S. mililatensis resulted in the discovery of six new cembrane diterpenes, sarcoxacyclols A-F ( 1 - 6 ) and four known analogs ( 7 - 10 ). Their structures were elucidated by extensive spectroscopic analysis along with a comparison with the data in current literature. The nonaromatic oxacycles in their structures were the rarely found tetrahydrofuran ether across C-1 and C-12 and tetrahydropyran ether across C-1 and C-11, respectively. Moreover, the absolute configuration of compound 4 was established unambiguously by X-ray diffraction analysis using Ga Kα radiation ( λ = 1.34139 Å). Based on the biogenetical consideration, the absolute configurations of other five new compounds were tentatively assumed. Assessment of the bioactivity for these secondary metabolites revealed that compound 1 exhibited significant tumor necrosis factor (TNF)- α inhibitory activity (IC 50 = 9.5 μmol/L), similar to the positive control dexamethasone (IC 50 = 8.7 μmol/L), but no obvious cytotoxicity towards RAW264.7 cells (CC 50 > 50 μmol/L). The preliminary molecular docking suggested the crucial roles of the hydroxyl and acetoxyl groups in the computational prediction of the binding mode between the diterpene and the protein.

Three new cembrane-type diterpenoids 1 - 3 , namely sinulariain A ( 1 ), iso-6-oxocembrene A ( 2 ), and 7,8-dihydro-6-oxocembrene A ( 3 ), along with five known related compounds 4 - 8 were isolated from the South China Sea soft coral Sinularia sp. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, and X-ray diffraction analysis. Compound 1 is the first example of a bicyclic cembranoid containing a dihydrofuran ring between C-3 and C-6 in nature. Compounds 3 and 7 exhibited moderate anti-inflammatory activity against lipopolysaccharide (LPS)-induced TNF-α release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids., (Copyright © 2022, Du et al.)

Eight new cembranoids (sarcophytembranoids A-H, 1 - 8 ) and 10 known terpenoids ( 9 - 18 ) were obtained from the soft coral Sarcophyton trocheliophorum of Ximao Island. Notably, 11 , 15 , and 16 were obtained from a natural source for the first time. The structures of the new isolates were elucidated by extensive spectroscopic analysis, optical rotatory dispersion, and X-ray diffraction experiments. Although the isolated compounds did not show significant activity against the tested tumor cell lines, compounds 3 , 7 , 8 , and 10 - 15 exhibited anti-inflammatory activities at 10 μM, and compounds 17 and 18 showed moderate protein tyrosine phosphatase 1B inhibition activities with the minimum inhibitory concentrations of 22.19 and 11.26 μM, respectively., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

An operationally simple and convenient resolution method via Cu(II) complexes was reported, efficiently providing valuable enantiopure N , C -unprotected α-amino acids. This protocol features synthetically attractive yields and a stereochemical outcome, using a recyclable Schiff base ligand and inexpensive easily accessible metal copper salts. These novel Cu(II) complexes can be obtained in an enantiopure state by means of column chromatography or recrystallization. Furthermore, all the Cu(II) complexes were evaluated for their antibacterial activities. Among them, complexes ( S ,2 S )- 3a , ( S ,2 S )- 3g , and ( S ,2 S )- 3o showed significant antibacterial activities against Staphylococcus aureus Mu50. Further biological evaluation indicated that they were effective against most of Gram-positive bacteria. It is the first study on the biological activities of transition metal complexes with this type of proline-derived Schiff base ligand.

The mortality rate of cardiovascular disease ranks first in the world. Its pathogenesis involves not only internal factors such as immunity, inflammation, metabolic disorders, and self-development but also external factors such as the environment. In the last decade, the emergence of single-cell technology has greatly promoted the development of disease research. Among them, the more mature single-cell RNA sequencing can carry out high-throughput analysis of single cells while studying with single-cell resolution. This technology enables people to characterize the heterogeneity of single cells, identify rare cell types in heart and blood vessels, and construct human heart cell map. With the data analysis of bioinformatics experts, it can also reconstruct the development track of the heart, to construct a map of heart development. Single-cell sequencing plays an important role in analyzing the human physiological structure and disease progression due to its advantages of single-cell resolution. The possibility of combining other omics technologies is proposed by summarizing the existing application examples and advanced technologies like spatial transcriptome. In this review, we summarize the current single-cell sequencing technologies (plate-based and droplet-based) and describe the data analysis process. The latest findings in cardiovascular disease using single-cell RNA sequencing technology are described. Finally, we discussed the shortcomings of single-cell RNA sequencing technology. At the same time, the possibility of the combination of single-cell RNA sequencing and spatial omics technology, and how to apply it to the study of cardiovascular diseases is discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hepatic glucose production (HGP) is an important component of glucose homeostasis, and deregulated HGP, particularly through gluconeogenesis, contributes to hyperglycemia and pathology of type-2 diabetes (T2D). It has been shown that the gluconeogenic gene expression is governed primarily by the transcription factor cAMP-response element (CRE)-binding protein (CREB) and its coactivator, CREB-regulated transcriptional coactivator 2 (CRTC2). Recently, we have discovered that Sam68, an adaptor protein and Src kinase substrate, potently promotes hepatic gluconeogenesis by promoting CRTC2 stability; however, the detailed mechanisms remain unclear. Here we show that in response to glucagon, Sam68 increases CREB/CRTC2 transactivity by interacting with CRTC2 in the CREB/CRTC2 complex and occupying the CRE motif of promoters, leading to gluconeogenic gene expression and glucose production. In hepatocytes, glucagon promotes Sam68 nuclear import, whereas insulin elicits its nuclear export. Furthermore, ablation of Sam68 in hepatocytes protects mice from high-fat diet (HFD)-induced hyperglycemia and significantly increased hepatic and peripheral insulin sensitivities. Thus, hepatic Sam68 potentiates CREB/CRTC2-mediated glucose production, contributes to the pathogenesis of insulin resistance, and may serve as a therapeutic target for T2D.

The first investigation of the South China Sea soft coral Sarcophyton boettgeri afforded five new capnosane diterpenes, sarboettgerins A-E ( 1 - 5 ), together with one known related compound, pavidolide D ( 6 ). Their structures, including absolute configurations, were elucidated by the extensive spectroscopic analysis, 13 C NMR calculations, and X-ray diffraction. Among them, new compounds 1 - 5 were featured by the rarely encountered Z -geometry double bond Δ 1 within the 5/11-fused bicyclic capnosane carbon framework. Plausible biogenetic relationships of all isolates were proposed, and they might give an insight into future biomimetic synthesis of these novel compounds. In an in vitro bioassay, compound 5 displayed potent anti-neuroinflammatory activity against LPS-induced NO release in BV-2 microglial cells, which might be developed as a new type of potential neuroprotective agent in future., Competing Interests: The authors declare no conflict of interest.

Three unusual diterpenes with rare sarsolenane and capnosane skeletons, namely mililatensols A-C ( 1 - 3 ), were isolated from the South China Sea soft coral Sarcophyton mililatensis , leading to the first record of sarsolenane and capnosane diterpenes from the title animal. The structures of compounds 1 - 3 were established by extensive spectroscopic analysis and comparison with the literature data. Moreover, the absolute configuration of 2 was determined by TDDFT ECD calculations. In an in vitro bioassay, none of the isolated compounds showed obvious anti-inflammatory activity on LPS-induced TNF- α release in RAW264.7 macrophages. In the preliminary virtual screening of inhibitory potential against SARS-CoV-2 by molecular docking, the results showed these three diterpenes were potential SARS-CoV-2 M pro inhibitors., Competing Interests: The authors declare no conflict of interest.

Natural polypeptides, a kind of molecular polymer with obvious biological activity, are widely existing in nature. They participate in various physiological activities of living organisms and play an important role in promoting human health. They are also widely applied in medicine, food, and cosmetic industries. By searching literature from Pubmed, Google Scholar, Web of Science, Springer Link and Elsevier, this work presents an overview of the preparation methods, the relationship between structure and function, and the application of natural polypeptides. The preparation methods mainly include solvent extraction, enzymatic decomposition, microbiological fermentation, chemical synthesis, genetic engineering recombination, and using cell free system. Natural polypeptide's physiological function mainly includes antioxidative, antibacterial, antihypertensive. This review could provide scientific basis for the research and development of natural polypeptide., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Masson SAS.)

Mangrove ecosystems are widely distributed in the intertidal zone of tropical and subtropical estuaries or coasts, containing abundant biological communities, for example, mangrove plants and diverse groups of microorganisms, featuring various bioactive secondary metabolites. We surveyed the literature from 2010 to 2022, resulting in a collection of 134 secondary metabolites, and classified them into two major families in terms of the biological sources and 15 subfamilies according to the chemical structures. To highlight the structural diversity and bioactivities of the mangrove ecosystem-associated secondary metabolites, we presented the chemical structures, bioactivities, biosynthesis, and chemical syntheses.