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Carbon fiber (CF) is a significant multifunction material, which is extensively used in aircraft because of its superb performance. However, its microwave absorption properties (MAPs) are seriously restricted as a result of the impedance mismatch issue. To address this issue, an efficient strategy is conducted by a series of CF@MoS 2 and CF@MoS 2 @Fe 3 O 4 composites that are fabricated by in-situ grown MoS 2 nanosheets (MoS 2 -NS) and Fe 3 O 4 nanoparticles (Fe 3 O 4 -NPs) on the surface of CF. The results of microwave absorption performance (MAP) reveal that the minimum reflection loss (RL) can reach −21.4 dB with a CF@MoS 2 composite coating thickness of 3.8 mm; the effective attenuation bandwidth (RL < −10 dB, i.e. , 90% microwave energy is attenuated) is up to 10.85 GHz (7.15–18.0 GHz). From a detailed analysis, it is observed impedance mismatch is the critical limiting factor for MAPs rather than attenuation. Furthermore, for CF@MoS 2 @Fe 3 O 4 , the MAP is strongly dependent on the level of coating of magnetic Fe 3 O 4 -NPs on the surface of CF@MoS 2 composites. The mechanisms underlying the superb MAP and related phenomena are investigated, opening new directions for fabricating CF-based microwave absorbers with high efficiency and wide-bandwidth. Finally, the occurrence of multi-reflection phenomena of EM waves in absorbers are critically analyzed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel 4-O-substituted phenyl indole-chalcones were designed via a structure-based design strategy. • FC11619 is an amino-containing indole-chalcone derivative with an improved water solubility. • FC11619 maintained the in vitro cytotoxicity against HCT-116 CRC in a low nanomolar range. • FC11619 significantly suppressed tumor growth, achieving 73.4 % at a dose of 10 mg/kg/d (i.v., 21 d). Advanced metastatic colorectal cancers (CRCs) are regarded as a challenge in clinical cancer therapy. Our previous studies have demonstrated that a representative fluoro-substituted indole-chalcone (FC116), was obtained to display highly potent activity against CRC using multiple in vitro and in vivo mouse models by targeting microtubules. However, several problems, such as low dose tolerance and highly toxic to the brain and colon, low solubility unsuitable for intravenous (i.v.) administration, are still existed and limit further development. Herein, we developed two series of FC116 derivatives on the 4-methoxyphenyl group by a structure-based design strategy. Among them, FC11619 with an amino terminus maintained the in vitro cytotoxicity against HCT-116 CRC in a low nanomolar range. This compound could induce G2/M phase arrest via regulating cyclin B1 expression, produce excess reactive oxygen species (ROS), and target tubulin in CRC cells. In vivo, FC11619 significantly suppressed tumor growth, achieving 65.3 and 73.4 % at doses of 5 and 10 mg/kg/d (i.v., 21 d), which were much better than 54.1% of Taxol at 7 mg/kg. In addition, this compound showed better in vivo tolerance compared to that of FC116 (only 3 mg/kg tolerance, intraperitoneal, i.p.), and no major organ-related toxicity, especially no apparent degenerated neurons, intestinal obstruction in clinical Taxol standard therapy. Taken together, the 4-amino-substitutedphenyl indole-chalcones represent lead compounds as chemotherapy of CRC for further drug development in this field. [ABSTRACT FROM AUTHOR]

A toolbox containing diverse Arg N -glycosylated peptides (glucose, galactose, 2-acetamino-2-deoxy-glucose, xylose, ribose, mannose, rhamnose, lactose and maltose), as well as the corresponding specific antibodies was develop. [Display omitted] Among posttranslational modifications, atypical arginine N- glycosylation has drawn increasing interest due to its fundamental role in various cellular procedures and signaling pathways. The efficient synthesis of arginine N- glycosylated substrates, as well as the generation of specific antibodies, remains challenging. This work describes the efficient synthesis of diverse arginine N -glycosylated peptides, in a process termed silver-promoted solid-phase glycosylation (SGG). There are two key features of the SSG strategy: (i) robust synthesis of gram-scale S-alkyl-isothiourea glycosyl donors facilitates the subsequent SSG procedure and (ii) the simultaneous introduction of both the side-chain sugar motif and arginine residue. Notably, our findings, combined with our previous results, provide a toolbox containing diverse S -alkyl-isothiourea glycosyl donors (glucose, galactose, mannose, ribose, xylose, lactose and maltose) as well as the corresponding Arg N -glycosylated peptides. In addition, our toolbox is shown to help investigate specific antibodies and identify multiple potent and precise biochemical tools for exploring arginine N -glycosylation. [ABSTRACT FROM AUTHOR]

Thonzonium bromide was identified as an inhibitor of SARS-CoV-2 3CLpro with an IC 50 value of 2.04 μM from the FDA-approved drug library, which inhibited the activity of SARS-CoV-2 3CLpro by firmly occupying the catalytic site and inducing conformational change of the protease. In addition, Thonzonium bromide has the broad-spectrum inhibitory activity against 3CLpro of human coronaviruses. [Display omitted] • Thonzonium bromide as a SARS-CoV-2 3CLpro inhibitor was screened by FRET-based enzymatic inhibition assay from the FDA-approved drug library. • Thonzonium bromide inhibited the activity of SARS-CoV-2 3CLpro by causing the change in the secondary structure of the protease. • Thonzonium bromide has the broad-spectrum inhibitory activity against 3CLpro of human coronaviruses. Although the effective drugs or vaccines have been developed to prevent the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), their efficacy may be limited for the viral evolution and immune escape. Thus, it is urgently needed to develop the novel broad-spectrum antiviral agents to control the coronavirus disease 2019 (COVID-19) global pandemic. The 3C-like protease (3CLpro) is a highly conserved cysteine proteinase that plays a pivotal role in processing the viral polyprotein to create non-structural proteins (nsps) for replication and transcription of SARS-CoV-2, making it an attractive antiviral target for developing broad-spectrum antiviral agents against SARS-CoV-2. In this study, we identified Thonzonium bromide as an inhibitor of SARS-CoV-2 3CLpro with an IC 50 value of 2.04 ± 0.25 μM by fluorescence resonance energy transfer (FRET)-based enzymatic inhibition assay from the FDA-approved drug library. Next, we determined the inhibitory activity of Thonzonium bromide analogues against SARS-CoV-2 3CLpro and analyzed their structure–activity relationship (SAR). Interestingly, Thonzonium bromide showed better inhibitory activity than other analogues. Further fluorescence quenching assay, enzyme kinetics analysis, circular dichroism (CD) analysis and molecular docking studies showed that Thonzonium bromide inhibited SARS-CoV-2 3CLpro activity by firmly occupying the catalytic site and inducing conformational changes of the protease. In addition, Thonzonium bromide didn't exhibit inhibitory activity on human chymotrypsin C (CTRC) and Dipeptidyl peptidase IV (DPP-IV), indicating that it had a certain selectivity. Finally, we measured the inhibitory activities of Thonzonium bromide against 3CLpro of SARS-CoV, MERS-CoV and HCoV-229E and found that it had the broad-spectrum inhibitory activity against the proteases of human coronaviruses. These results provide the possible mechanism of action of Thonzonium bromide, highlighting its potential efficacy against multiple human coronaviruses. [ABSTRACT FROM AUTHOR]

Non-cardiomyocytes (non-CMs) play an important role in the process of cardiac remodeling of chronic heart failure. The mechanism of non-CMs transit and interact with each other remains largely unknown. Here, we try to characterize the cellular landscape of non-CMs in mice with chronic heart failure by using single-cell RNA sequencing (scRNA-seq) and provide potential therapeutic hunts. Cellular and molecular analysis revealed that the most affected cellular types are mainly fibroblasts and endothelial cells. Specially, Fib_0 cluster, the most abundant cluster in fibroblasts, was the only increased one, enriched for collagen synthesis genes such as Adamts4 and Crem, which might be responsible for the fibrosis in cardiac remodeling. End_0 cluster in endothelial cells was also the most abundant and only increased one, which has an effect of blood vessel morphogenesis. Cell communication further confirmed that fibroblasts and endothelial cells are the driving hubs in chronic heart failure. Furthermore, using fibroblasts and endothelial cells as the entry point of CMap technology, histone deacetylation (HDAC) inhibitors and HSP inhibitors were identified as potential anti-heart failure new drugs, which should be evaluated in the future. The combined application of scRNA-seq and CMap might be an effective way to achieve drug repositioning. [Display omitted] • Comprehensive transcriptional landscape of non-cardiomyocytes in the failing heart of mice. • Detection of major cell types and characterization of transcriptional heterogeneity. • Identified and characterized unique fibroblasts and endothelial cells subcluster. • Cell-Cell communication patterns after heart failure • Identified HDAC inhibitors and HSP inhibitors as potential anti-heart failure new drugs [ABSTRACT FROM AUTHOR]

• GA derivatives with fused heterocycles on A ring were structure-based designed and synthesized. • GA-60 could bind to HMGB1. • GA-60 extended survival in LPS/CLP induced mouse models of sepsis. • GA-60 exhibited excellent inhibitory functions on NO, TNF-α, and IL-6. • GA-60 could interfere with MAPKs and NF-κB. Novel Glycyrrhetinic Acid (GA) derivatives with fused heterocycles on A ring were structure-based designed and synthesized. Their potential anti-inflammatory effects were investigated by a classical LPS stimulated macrophage model. Surface plasmon resonance (SPR) was used to verify the binding of GA analogues with HMGB1. A preliminary structure–activity relationship was summarized and an analogue GA-60 with ortho -methoxybenzyl pyrozole showed stronger anti-inflammatory effect and higher affinity for HMGB1 with a K d value of 12.5 μM. In addition, this compound exhibited excellent inhibitory functions on NO (96%), TNF-α (94%), and IL-6 (100%), by interfering with phosphorylation of p38, ERK, JNK MAPKs, as well as that of NF-κB p65 and IKKα/β. Moreover, GA-60 extended the survival of either the classic CLP-induced or LPS-induced sepsis mouse models. Molecular modeling predictions further supported these findings, clearly indicating that inhibiting HMGB1 release, using fused heterocyclic GA derivatives, is a promising strategy for treatment of sepsis. [ABSTRACT FROM AUTHOR]

Seven new guaiane-type sesquiterpene dimers vieloplains A-G, connecting mode (C-3 to C-3′, C-4 to C-1′), (C-2 to C-3′, C-4 to C-2′) and (C-2 to C-1′ , C-4 to C-2′) , were isolated from the roots of Xylopia vielana. Flow cytometry analysis confirmed that 6 caused death of DU145 cells via apoptosis induction. • Seven new guaiane-type sesquiterpene dimers vieloplains A-G, connecting patterns through three different direct C C bonds, were isolated from the roots of Xylopia vielana. • Their absolute configurations were established by NOESY analysis, the Cu K α X-ray crystallographic the experiment circular dichroism (ECD) and the calculated ECD. Seven new guaiane-type sesquiterpene dimers vieloplains A-G, connecting patterns through three different direct C C bonds compounds 1 – 5 (C-3 to C-3′, C-4 to C-1′), compound 6 (C-2 to C-3′, C-4 to C-2′) and compound 7 (C-2 to C-1′ , C-4 to C-2′) were isolated from the roots of Xylopia vielana. Their absolute configurations were established by NOESY analysis, the Cu K α X-ray crystallographic the experiment circular dichroism (ECD) and the calculated ECD. Among them, only compound 6 showed a considerable cytotoxicity against DU145 cells with IC 50 values of 9.5 μM. Flow cytometry analysis confirmed that 6 caused death of DU145 cells via apoptosis induction. [ABSTRACT FROM AUTHOR]