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The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1 – 4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4–8 μg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time. [Display omitted] • Resorcylic acid derivatives from Lysimachia tengyuehensis as major bioactivity rapidly killed MRSA and VRE within 40 min. • Resorcylic acid derivatives disrupted bacterial biofilm and cell membrane homeostasis by interfering with bacterial metabolic imbalance. • Resorcylic acid derivatives might be bactericides with potent applications in treating skin and peritoneal infections. [ABSTRACT FROM AUTHOR]

[Display omitted] • Morusin killed MRSA quickly by the dual mechanism with H 2 S inhibition and membrane damage. • Morusin broken the homeostasis of MRSA between H 2 S and ROS by inhibiting the production of H 2 S and accumulating ROS. • Morusin could be developed as an antibacterial agent to overcome MDR-MRSA without drug resistance. It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H 2 S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin. [ABSTRACT FROM AUTHOR]

Objective: To explore new therapies for castration-resistant prostate cancer to improve patients' quality of life and extend life.Materials and Methods: The synthesis, morphology analysis, phase analysis, spectral analysis, and photothermal conversion test were referenced to our previous articles. Then near-infrared light-driven copper sulfide (CuS) nanoplates to inhibit the growth of prostate cancer cells in vivo and in vitro was carried out. Transmission electron microscope, mCherry-LC3 syncytial virus labeling, acridine orange staining, and autophagy protein were used to detect the autophagy caused by CuS nanoplates and chloroquine was used to inhibit the process of autophagy.Results: The CuS nanoplates prepared in this study feature low cytotoxicity, simple preparation, and high photothermal conversion efficiency. Driven by 980 nm near-infrared light, CuS nanoplates could inhibit the growth of prostate cancer cells in vivo and in vitro, while triggering the autophagy and cytoprotection of prostate cancer cells.Conclusion: CuS nanoplates are a kind of commendable photothermal therapy agent in castration-resistant prostate cancer treating. Autophagy inhibition enhances the photothermal efficiency of CuS nanoplates, which indicates favorable application prospects in the treatment of advanced prostate cancer. [ABSTRACT FROM AUTHOR]

High borated steels (HBSs) exhibit poor mechanical properties because brittle and coarse borides served as crack source during deformation, causing a premature failure. Here we proposed a novel strategy of tailoring strain hardening behaviour of metal matrix to enhance performance. Metastable austenite was introduced as matrix, where various deformation mechanism was obtained by manipulating deform temperature to change stacking fault energy (SFE). Unexpectedly, extraordinary strength-ductility synergy was achieved in HBSs with a moderate SFE at 100 °C. During hetero-deformation, hard borides caused serious stress gradients in austenite, triggering discontinuous transformation-induced plasticity effect. The cavities originating from fractured borides and interface debonding were arrested effectively by transformed martensite, which highly retarded the coalescence to form large cracks, allowing residual strain hardening to extend much longer to induce additional ductility. This work provides a new pathway to enhance strength-ductility synergy of materials containing many coarse and brittle secondary phases. [Display omitted] [ABSTRACT FROM AUTHOR]

Infectious diseases caused by multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus , pose a significant threat to humanity. Persistent and repeated invasive infection with MRSA led to higher morbidity and mortality, and required comprehensive measures in treatment and prevention. Zanthoxylum nitidum (Roxb.) DC. is used as detoxifying, analgesic, and hemostatic herbal medicine for thousands of years. Previously pharmacological studies showed that Z. nitidum had antibacterial bioactivity, but only the MIC of a few compounds, crude extracts, and fractions were reported. In our ongoing endeavor to explore bioactive compounds, two new coumarins, 6-(3-oxo-butyl)-limettin (1) and toddalin I (2), and 24 known compounds were isolated from the roots of Z. nitidum , in which two isoquinoline alkaloids, 6-acetonyl-dihydrofagaridine (16) and 6-acetonyl-dihydrochelerythrine (17) showed anti-MRSA bioactivity in vitro and in vivo. Both 16 and 17 showed synergistic action with ampicillin, which decreased the MIC significantly, and both compounds had a significant ability to destroy bacterial biofilm combined with ampicillin. The combined administration showed a strong scavenging effect on the planktonic bacteria in vitro and cleared skin infection effectively in the model of wound infection in vivo. Furthermore, compound 16 inhibited the efflux of the drug by combining with ampicillin or EtBr, resulting in the MIC decreased obviously. Our investigation supported the traditional use of Z. nitidum in treating infections caused by bacteria, and might provide new natural products to reduce the use of antibiotics and the treatment of drug-resistance bacteria. [Display omitted] • Two new coumarins, and 24 known compounds were isolated from Zanthoxylum nitidum. • Two isoquinoline alkaloids showed anti-MRSA bioactivity and synergistic action with ampicillin in vitro indicated. • Skin infections of mouse were effectively treated by the compounds in combination with ampicillin. • The compound inhibited the efflux of the drug by combining with ampicillin. [ABSTRACT FROM AUTHOR]

The zanthoxylum herbs are the dual-purpose Chinese herbal medicine and functional food favored by East and Southeast Asians. In this study, nematicidal and antibacterial major active components among ten typical zanthoxylum herbs (ethanol extracts) were investigated comprehensively by high resolution mass spectrometry. The major ingredients and their contents were analyzed, especially summarizing the typical fragment ions of alkaloids, amides, lignans, and coumarins of zanthoxylum herbs. We found that ethanol extracts of zanthoxylum herbs showed significantly high antibacterial properties. The MICs values of Zanthoxylum piasezkii Maxim (CJ), Zanthoxylum khasianum Hook (HJ), and Zanthoxylum armatum DC (ZYHJ) with S. aureus , MRSA, S. hemolyiicus and C. albicans were 0.1–0.5 mg/mL, respectively. In addition, CJ extract (1 mg/mL) had a significant effect on killing nematode eggs (p < 0.001). Through the multivariate analysis, we found that the main components of the CJ and ZYHJ in antibacterial activities are similar. The content of amides was less in CJ, but its nematicidal capacity was better. The results provided a valuable guidance for the chemical differentiation and proper application of zanthoxylum herbs in the fields of functional foods and medicinal herbs. [Display omitted] [ABSTRACT FROM AUTHOR]

Six pairs of previously undescribed enantiomeric phytocannabinoid-like meroterpenoids, (±)-spinulinoids A‒F, and two naturally occurring compounds, (+)-rhododaurichromanic acid A and (E)-4-((3,7-dimethylocta-2,6-dien-1-yl)oxy)benzoic acid, together with one known congener, (−)-rhododaurichromanic acid A, were obtained from the twigs and leaves of Rhododendron spinuliferum. Their structures were established by their extensive spectral data (NMR and HRESIMS), ECD calculations, and single-crystal X-ray diffraction data. Spinulinoids A and B are unprecedented phytocannabinoid-like meroterpenoids constructed by the resorcinol moiety and a β -bisabolene unit, whereas spinulinoid C represents a rare adduct of quinone and β -bisabolene with a tricyclic 6/6/6 ring system. Three undescribed phytocannabinoid-like meroterpenoids, spinulinoids A‒C, were isolated from Rhododendron spinuliferum. [Display omitted] • Six undescribed phytocannabinoid-like meroterpenoids were obtained from R. spinuliferum. • Their structures were elucidated by a combination of spectroscopic data analyses. • Spinulinoids A‒C are structurally intriguing phytocannabinoid-like meroterpenoids. • Structural types of meroterpenoids in Rhododendron genus were further enriched. [ABSTRACT FROM AUTHOR]

Here we for the first time reported the heterogeneous nucleation of orthorhombic M 2 B-type borides (M = Cr, Fe) attached to TiB 2 and Ti(C,N) particles with a specific crystallographic orientation relationship (OR) in as-cast boron-containing steel. The ORs were identified as 0001 Ti B 2 ∥ 1 ¯ 1 2 ¯ M 2 B , 1 2 ¯ 10 Ti B 2 ∥ 31 1 ¯ M 2 B and 001 Ti C N ∥ 13 6 ¯ M 2 B , 100 Ti C N ~ ∥ 3 1 ¯ 0 M 2 B. The transmission electron microscopy characterization and lattice misfit calculation showed that the interfaces of TiB 2 /M 2 B and Ti(C,N)/M 2 B were semi-coherent. The heterogeneous nucleation efficiency was investigated in terms of an interfacial energy calculation based on the misfit dislocation theory. Unlabelled Image • Alloying titanium refined and dispersed M 2 B borides in as-cast borated steels. • M 2 B borides nucleated on TiB 2 and Ti(C,N) particles during solidification. • The morphology of M 2 B borides changed from lamellar-like to grainy-like. • The interfaces of TiB 2 /M 2 B and Ti(C,N)/M 2 B were semi-coherent. • The interfacial energies of TiB 2 /M 2 B and Ti(C,N)/M 2 B interfaces were very low. [ABSTRACT FROM AUTHOR]

The expansion of the global population and improved living standards has created an increasing demand for fresh fruit. The combination of agricultural and medical development for new fungicides is one of the most effective approaches for keeping fruit fresh. Both amphotericin B and 5-flucytosine are quite safe and have a wide spectrum of antifungal activity. For the purpose of investigating their potential applications for preserving fruit freshness, we evaluated their antifungal efficiencies against Penicillium italicum in vitro and in vivo. The results showed that amphotericin B and 5-flucytosine significantly inhibited spore germination and the mycelial growth of P. italicum. The 5-flucytosine showed much better bioactivity than the well-known agricultural fungicide prochloraz, both in vitro and in vivo. Furthermore, crystal violet staining, propidium iodide dyeing, ultrastructural observation and the ergosterol content indicated that amphotericin B and 5-flucytosine destroyed the cellular ultrastructure and membrane integrity. In addition, nucleic acids (OD 260) and proteins (OD 280) escaped from P. italicum cells in a dose-dependent manner. The results of this study indicated that amphotericin B and 5-flucytosine have good potential as antifungal preservatives for postharvest citrus fruit due to their excellent antifungal effects, and that the primary mode of action was the destruction of the membrane integrity and permeability of P. italicum. • Amphotericin B and 5-flucytosine have potent activities against Penicillium italicum. • Amphotericin B and 5-flucytosine deformed the morphology of P. italicum. • Amphotericin B and 5-flucytosine destroyed plasma membrane integrity. • Amphotericin B and 5-flucytosine controlled blue mold on postharvest citrus. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25–1.00 μg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin. [Display omitted] • Guided synthesis of flavonoid derivatives from 162 natural flavonoids. • Amphiphilic flavonoid derivatives displayed broad-spectrum antibacterial activity. • K15 avoided resistance by damaging biofilm and targeting cell membranes. • K15 exhibited excellent therapeutic effect in vivo , superior to vancomycin and ampicillin. [ABSTRACT FROM AUTHOR]

Allium chinense G. Don is a popular medicinal and aromatic plant, known as "Ganoderma of vegetables" in history for treating blood stasis syndrome that reduces red blood cell oxygen-carrying capacity and often causes severe brain damage. However, the effect of A. chinense on cerebral anoxia remains obscure. Here, the anti-hypoxic effect of A. chinense was investigated for the first time through the cerebral anoxia model of mice. Subsequent a bio-guided investigation brought about the isolation of 16 compounds, including 9 phenolic derivatives (2 new compounds (compound 1, 8) and one new natural product (compound 2), 4 steroidal saponins and 3 fatty acid monoglycerides, among which, 6 compounds (1–4 , 7 , 16) exhibited significant anoxia-tolerant activity in vitro. Moreover, the release of reactive oxygen species (ROS) was decreased significantly, and glutathione (GSH) and lactate dehydrogenase (LDH) were regulated by the 6 bioactive compounds in oxygen‑glucose deprivation/ reoxygenation (OGD/R)-induced BV-2 cells damage. Besides that, protein expressions of HIF-1 α , NLRP3, COX-2, NF- κ B p65 and IL-18 were suppressed effectively. The investigation provided a new nutritional strategy for A. chinense against cerebral anoxia and altitude illness, which might be partially mediated by downregulating NLRP3/NF- κ B. [Display omitted] • The anoxia-tolerant activity of A. chinense was studied for the first time. • Bio-guided investigation led to the isolation of 16 compounds, including three new compounds. • Bioactive compounds improved anoxia-tolerant ability may be associated to regulating NLRP3/NF- κ B. • It may be a source for sustainable foods, dietary supplements and pharmaceutical use. [ABSTRACT FROM AUTHOR]

In this work, a 0.71 wt%Si+0.44 wt%Al as-cast strip was produced by novel twin-roll casting. Some as-cast samples were respectively reheated and hot rolled at different temperatures in order to obtain different microstructure prior to cold rolling and annealing. The effects of the hot rolled microstructure on microstructure, texture evolution and magnetic properties were investigated in detail. A coarse deformed microstructure with λ-fiber texture was formed after hot rolling at 850–1050 °C, finally leading to an inhomogeneous recrystallization microstructure with strong λ-fiber, Goss and extremely weak γ-fiber texture. By contrast, a fine transformed microstructure was formed after hot rolling at 1150–1250 °C, finally leading to a fine and homogeneous recrystallization microstructure with stronger α-fiber, γ-fiber and much weaker λ-fiber texture. It should be noted that both the magnetic induction and core loss non-monotonically decreased or increased according to the hot rolling temperature. The unfavorable α-fiber and γ-fiber textures in the annealed sheets were much weaker than those of the conventional products regardless of the hot rolling temperature, thus contributing to a much higher magnetic induction. However, the average grain size in the annealed sheets was much lower than those of the conventional products regardless of the hot rolling temperature, thus leading to a higher core loss except the case of 1050 °C. Hence, it is underscored that better integrated magnetic properties than those of the conventional products can be obtained by optimizing the hot rolled microstructure to produce final desirable recrystallization microstructure and texture. [ABSTRACT FROM AUTHOR]

Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC 50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 μM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation. [ABSTRACT FROM AUTHOR]